Gene Summary

Gene:PTEN; phosphatase and tensin homolog
Aliases: BZS, DEC, CWS1, GLM2, MHAM, TEP1, MMAC1, PTEN1, 10q23del
Summary:This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
Source:NCBIAccessed: 14 March, 2017


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

As tumours progress to more advanced stages, they tend to acquire an increasing number of genetic alterations. One common alteration seen in a range of different advanced cancers is mutation of the PTEN gene, a gene which is linked with cell regulation and apoptosis (programmed cell death). Mutations in the PTEN gene are documented in cancers of the breast, prostate, endometrium, ovary, colon, melanoma, glioblastoma. and lymphoma. Animal models have shown that the loss of just one copy of the PTEN gene is enough to interrupt cell signalling and begin the process of uncontrolled cell growth. However, the significance of PTEN alterations in carcinogenesis is controversial since aberrant transcripts of PTEN have also been identified in normal non-cancerous tissues.

Research Indicators

Publications Per Year (1992-2017)
Graph generated 14 March 2017 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 14 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (16)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Breast CancerPTEN and Breast Cancer View Publications536
Prostate CancerPTEN and Prostate Cancer View Publications502
Endometrial CancerPTEN mutations in Endometrial Cancer
Mutations of the PTEN suppressor gene are the most frequent genetic abnormality in endometrial cancers. They occur in 40-80% of endometrioid carcinomas, which account for the majority of endometrial cancers. PTEN mutations have also been detected in the precancerous condition endometrial intraepithelial neoplasia.
View Publications497
Brain and CNS TumoursPTEN and Glioblastoma View Publications443
Astrocytoma, ChildhoodPTEN and Astrocytoma View Publications441
Lung CancerPTEN and Lung Cancer View Publications405
Cowden SyndromePTEN mutations in Cowdon Syndrome
Cowdon Syndrome is a hereditary disease characterised by multiple ectodermal, mesodermal, and endodermal nevoid abnormalities. People with the syndrome have an elevated risk of breast cancer, thyroid cancer and endometrial cancer.
View Publications307
Thyroid CancerPTEN and Thyroid Cancer View Publications143
Skin CancerPTEN and Skin Cancer View Publications112
Stomach CancerPTEN and Stomach Cancer View Publications93
Soft Tissue SarcomaPTEN and Soft Tissue Sarcoma View Publications83
-PTEN in Precancerous Conditions
PTEN mutations are implicated in a number of precancerous conditions. For example Mutter and colleagues (JNCI, 2000) found 16/29 (55%) of endometrial intraepithelial neoplasia (a precancerous condition) had PTEN mutations compared to 25/30 (83%) of endometrioid adenocarcinomas. They suggest that PTEN may be a useful immunohistochemical biomarker for premalignant disease. The precancers were characterised by mutation of only 1 PTEN allele while the adenocarcinomas showed reduced or complete loss of PTEN protein expression.
View Publications59
MesotheliomaPTEN expression in Mesothelioma View Publications19
Salivary Gland CancerPTEN and Salivary Gland Cancer View Publications19
Testicular CancerPTEN and Testicular Cancer View Publications12
Ewing's SarcomaPTEN Amplification in Ewing's Sarcoma?
In a genome-wide copy-number analysis of Ewing's sarcoma, Lynn et al (2013) found localized copy-number alterations of PTEN.
View Publications6

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: PTEN (cancer-related)

Zhou S, Zhang S, Shen H, et al.
Curcumin inhibits cancer progression through regulating expression of microRNAs.
Tumour Biol. 2017; 39(2):1010428317691680 [PubMed] Related Publications
Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

Pectasides D, Kotoula V, Papaxoinis G, et al.
Expression Patterns of Growth and Survival Genes with Prognostic Implications in Advanced Pancreatic Cancer.
Anticancer Res. 2016; 36(12):6347-6356 [PubMed] Related Publications
AIM: The aim of this study was to evaluate the mRNA expression pattern of growth- and survival-related genes and assess their prognostic significance in patients with advanced pancreatic cancer.
PATIENTS AND METHODS: In total, 98 patients were included in this retrospective translational research study and were evaluated for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutational status, and v-akt murine thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), hepatocellular growth factor receptor (MET), avian myelomatosis viral oncogene homolog (MYC), nuclear factor kappa B subunit 1 (NFKb1), phosphatase and tensin homolog (PTEN) and mechanistic target of rapamycin (FRAP1) genes mRNA expression. Among these patients, 73 received first-line gemcitabine combined with erlotinib (N=57) or gefitinib (N=16).
RESULTS: KRAS mutation did not correlate with mRNA gene expression. Unsupervised hierarchical clustering according to mRNA gene expression successfully distinguished four prognostically distinct groups of tumors. Overexpression of all genes was associated with best prognosis, while suppression or heterogeneous expression patterns of the examined genes were associated with expression patterns of growth- and survival-related genes, classifying pancreatic tumors into distinct groups with possibly different outcomes.

Zhang L, Jia G, Shi B, et al.
PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma.
Cell Physiol Biochem. 2016; 40(3-4):757-769 [PubMed] Related Publications
BACKGROUND: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC).
METHODS: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed. The role of PRSS8 in cell proliferation, apoptosis and invasion were examined in vitro and in vivo.
RESULTS: PRSS8 mRNA and protein expression were decreased in most HCC tumours from that in matched adjacent non-tumour tissues. Low intratumoral PRSS8 expression was significantly correlated with poor overall survival (OS) in patients with HCC (P = 0.001). PRSS8 expression was an independent prognostic factor for OS (hazard ratio [HR] = 1.704, P = 0.009). Furthermore, restoring PRSS8 expression in high metastatic HCCLM3 cells significantly inhibited cell proliferation and invasion. In contrast, silencing PRSS8 expression in non-metastatic HepG2 cells significantly enhanced cell growth and invasion. Moreover, our in vivo data revealed that attenuated PRSS8 expression in HepG2 cells greatly promoted tumour growth, while overexpression of PRSS8 remarkably inhibited tumour growth in an HCCLM3 xenograft model. Enhanced cell growth and invasion ability mediated by the loss of PRSS8 expression was associated with downregulation of PTEN, Bax and E-cadherin and an upregulation in Bcl-2, MMP9 and N-cadherin.
CONCLUSIONS: Our data demonstrate that PRSS8 may serve as a tumour suppressor in HCC progression, and represent a valuable prognostic marker and potential therapeutic target for HCC.

Grimes JA, Prasad N, Levy S, et al.
A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs.
BMC Vet Res. 2016; 12(1):272 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Splenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal.
RESULTS: Twenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma.
CONCLUSIONS: Findings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.

Cui L, Li Y, Lv X, et al.
Expression of MicroRNA-301a and its Functional Roles in Malignant Melanoma.
Cell Physiol Biochem. 2016; 40(1-2):230-244 [PubMed] Related Publications
BACKGROUND/AIMS: Although microRNA-301a has been reported to function as an oncogene in many human cancers, the roles of miR-301a in malignant melanoma (MM) is unclear. The present study aims to investigate the functional roles of miR-301a in MM and its possible molecular mechanisms.
METHODS: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of miR-301a in MM tissues, and analyze its correlation with metastasis and prognosis of MM patients. In vitro, miR-301a was ectopically expressed using overexpression and knock-down strategies, and the effects of miR-301a expression on growth, apoptosis, migration, invasion and chemosensitivity of MM cells were further investigated. Furthermore, the potential and functional target gene was identified by luciferase reporter, qRT-PCR, Western blot assays.
RESULTS: We showed that the expression of miR-301a was significantly upregulated in MM tissues, and upregulation of miR-301a correlated with metastasis and poor prognosis of MM patients. Transfection of miR-301a/inhibitor significantly inhibited growth, colony formation, migration, invasion and enhanced apoptosis and chemosensitivity in MM cells, while transfection of miR-301a/mimic could induce the inverse effects on phenotypes of MM cells. Luciferase reporter, qRT-PCR and Western blot assays showed that phosphatase and tensin homolog (PTEN) was a direct and functional target of miR-301a. It was also observed that the Akt and FAK signaling pathways were involved in miR-301/PTEN-promoting MM progression.
CONCLUSION: Taken together, our study suggests that miR-301a may be used as a potential therapeutic target in the treatment of human MM.

Lu XX, Cao LY, Chen X, et al.
PTEN Inhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERT Pathway in Lung Adenocarcinoma A549 Cells.
Biomed Res Int. 2016; 2016:2476842 [PubMed] Free Access to Full Article Related Publications
PTEN plays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role of PTEN in lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutant PTEN as well as A549 cells expressing a siRNA directed toward endogenous PTEN. Overexpression of wild-type PTEN profoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase protein hTERT. In contrast, in cells expressing a PTEN directed siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, and hTERT protein expression were observed. A549 cells transfected with a PTEN mutant lacking phosphatase activity (PTEN-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects of PTEN. Taken together, we have demonstrated that PTEN downregulates the PI3K/AKT/hTERT pathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.

Li Y, Xu T, Zou H, et al.
Cell migration microfluidics for electrotaxis-based heterogeneity study of lung cancer cells.
Biosens Bioelectron. 2017; 89(Pt 2):837-845 [PubMed] Related Publications
Tumor metastasis involves the migration of cells from primary site to a distant location. Recently, it was established that cancer cells from the same tumor were heterogeneous in migratory ability. Numerous studies have demonstrated that cancer cells undergo reorientation and migration directionally under physiological electric field (EF), which has potential implications in metastasis. Microfluidic devices with channel structures of defined dimensions provide controllable microenvironments to enable real-time observation of cell migration. In this study, we developed two polydimethylsiloxane (PDMS)-based microfluidic devices for long-term electrotaxis study. In the first chip, three different intensities of EFs were generated in a single channel to study cell electrotactic behavior with high efficiency. We observed that the lung adenocarcinoma H1975 cells underwent cathodal migration with changing cellular orientation. To address the issue of cell electrotactic heterogeneity, we also developed a cell isolation device integrating cell immobilization structure, stable EF generator and cell retrieval module in one microfluidic chip to sort out different cell subpopulations based on electrotactic ability. High electrotactic and low electrotactic cells were harvested separately for colony formation assay and transcriptional analysis of migration-related genes. The results showed that H1975 cell motility was related to EGFR expression in the absence of EF stimulation, while in the presence of EF it was associated with PTEN expression. Up-regulation of RhoA was observed in cells with high motility, regardless of EF. The easy cell manipulation and precise field control of the microfluidic devices may enable further study of tumor heterogeneity in complex electrotactic environments.

Tusong H, Maolakuerban N, Guan J, et al.
Functional analysis of serum microRNAs miR-21 and miR-106a in renal cell carcinoma.
Cancer Biomark. 2017; 18(1):79-85 [PubMed] Related Publications
OBJECTIVE: microRNAs (miRNAs) plays an important role in tumor development and progression and act as oncogenes or tumor suppressor genes in the carcinogenesis process. miRNA is stable in serum, and recent studies have demonstrated the feasibility of using circulating miRNA as biomarkers in cancer patients. However, currently, no serum biomarkers for the early diagnosis and prognosis of renal cell carcinoma (RCC) have been reported. Therefore, a new molecular marker for early diagnosis and evaluation of recurrence after surgery is required. Our purpose was to identify miRNA signatures that could distinguish the serum of RCC patients from matched healthy controls and validate identified miRNAs as potential biomarkers for RCC.
METHOD: Serum samples from 30 RCC patients were collected before and 1 month after surgery. 30 cancer-free blood donor volunteers with no history of any cancer were recruited from the same institute. miR-21 and miR-106a expression levels were determined by real-time PCR.
RESULT: The serum miR-21 level was significantly higher in RCC patients (median, 8.34) than in healthy control individuals (median, 0.70; p= 0.001). A month after surgery, serum miR-21 levels (median, 0.69) were significantly reduced (p= 0.032). The serum miR-106a level was higher in RCC patients (median, 8.99) compared with controls (median, 0.96; p= 0.000), while miR-106a levels (median, 1.01) were reduced a month after surgery (p= 0.028). The expression level of miR-21 and miR-106 a in RCC patients increased significantly, while miR-21 and miR-106a decreased after surgery. This outcome suggests that serum miR-21 and miR-106a expression level was closely related with kidney cancer tissue.
CONCLUSION: We conclude that serum miR-21 and miR106a are expected to be molecular markers for RCC.

Zhou B, Wang J, Zheng G, Qiu Z
Methylated urolithin A, the modified ellagitannin-derived metabolite, suppresses cell viability of DU145 human prostate cancer cells via targeting miR-21.
Food Chem Toxicol. 2016; 97:375-384 [PubMed] Related Publications
Urolithins are bioactive ellagic acid-derived metabolites produced by human colonic microflora. Although previous studies have demonstrated the cytotoxicity of urolithins, the effect of urolithins on miRNAs is still unclear. In this study, the suppressing effects of methylated urolithin A (mUA) on cell viability in human prostate cancer DU145 cells was investigated. mUA induced caspase-dependent cell apoptosis, mitochondrial depolarization and down-regulation of Bcl-2/Bax ratio. The results showed that upon exposure to mUA, miR-21 expression was decreased and the expression of PTEN and Pdcd4 protein was elevated. mUA could further suppress Akt phosphorylation and increase protein expression of FOXO3a, and the effects of mUA on Akt phosphorylation and protein expression of FOXO3a were blocked by PTEN silence. Moreover, mUA suppressed the Wnt/β-catenin-mediated transcriptional activation of MMP-7 and c-Myc, and this function of mUA on MMP-7 and c-Myc was attenuated by over-expression of miR-21. In conclusion, our data suggest that mUA can suppress cell viability in DU145 cells through modulating miR-21 and its downstream series-wound targets, including PTEN, Akt and Wnt/β-catenin signaling.

Siddiqui S, Akhter N, Deo SV, et al.
A study on promoter methylation of PTEN in sporadic breast cancer patients from North India.
Breast Cancer. 2016; 23(6):922-931 [PubMed] Related Publications
BACKGROUND: Epigenetic silencing of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through DNA methylation has been implicated in the pathogenesis of breast cancer. Present study investigates the contribution of PTEN promoter methylation and its associated protein expression in sporadic breast cancer patients from North India.
METHODS: A total of 360 paired breast carcinoma and adjacent normal tissue samples from 180 sporadic breast cancer patients were included in the present study and examined for PTEN promoter methylation status by methylation-specific polymerase chain reaction. Immunohistochemistry method was used for determining PTEN protein expression. Molecular findings were statistically correlated with various clinicopathological parameters to identify associations of clinical relevance.
RESULTS: Presence of PTEN promoter methylation (39.44 %) significantly correlated with its expression downregulation (45.56 %) in breast tumors (P = 0.0001). Furthermore, their interaction with various clinical parameters was evidenced in stratified analysis. Correlation of PTEN promoter methylation with histologically more malignant grade and PTEN expression loss with triple negative tumor status remained significant even after Bonferroni correction (P < 0.003).
CONCLUSIONS: Results implicate promoter methylation to be a mechanism partially responsible for PTEN silencing in sporadic breast cancer for North Indian women. Besides, methylation and expression loss of PTEN exhibited promising potential as candidate biomarkers of risk assessment in subcategorized breast tumors with critical pathologic parameters.

Burdelski C, Dieckmann T, Heumann A, et al.
p16 upregulation is linked to poor prognosis in ERG negative prostate cancer.
Tumour Biol. 2016; 37(9):12655-12663 [PubMed] Related Publications
Altered expression of the p16 tumor suppressor is frequently found in prostate cancer, but its role for tumor development and patient prognosis is disputed. In order to clarify the prognostic role of p16 and to draw conclusions on interactions with key molecular features of prostate cancer, we studied p16 expression in a tissue microarray (TMA) with more than 12,400 prostate cancers and attached clinical, pathological, and molecular data such as ERG status and deletions of 3p13, 5q21, 6q15, and PTEN. p16 immunostaining was absent in non-neoplastic prostate cells but was found in 37 % of 9627 interpretable prostate cancers. Finding p16 expression in 58 % of ERG positive but in only 22 % of ERG negative cancers (p < 0.0001), highlights the known androgen-dependence of both genes. Significant associations between p16 upregulation and tumor phenotype or patient prognosis were strictly limited to the subset of ERG negative cancers. For example, p16 positivity increased from 15 % in Gleason ≤3 + 3 to 38 % in Gleason ≥4 + 4 cancers (p < 0.0001) and was associated with early PSA recurrence (p < 0.0001). p16 upregulation was strongly linked to deletions of PTEN (p < 0.0001), highlighting the interaction of both genes in growth control. In conclusion, p16 upregulation is a strong prognostic factor in ERG negative cancers. The strict limitation of its prognostic impact to a molecularly defined subgroup challenges the concept of molecular prognosis testing without considering molecular subtypes.

Gao S, Zhu L, Feng H, et al.
Gene expression profile analysis in response to α1,2-fucosyl transferase (FUT1) gene transfection in epithelial ovarian carcinoma cells.
Tumour Biol. 2016; 37(9):12251-12262 [PubMed] Related Publications
The aim of this study was to identify differentially expressed genes (DEGs) in response to α1,2-fucosyl transferase (FUT1) gene transfection in epithelial ovarian cancer cells. Human whole-genome oligonucleotide microarrays were used to determine whether gene expression profile may differentiate the epithelial ovarian cell line Caov-3 transfected with FUT1 from the empty plasmid-transfected cells. Quantitative real-time PCR and immunohistochemical staining validated the microarray results. Gene expression profile identified 215 DEGs according to the selection criteria, in which 122 genes were upregulated and 93 genes were downregulated. Gene Ontology (GO) and canonical pathway enrichment analysis were applied, and we found that these DEGs are involved in BioCarta mammalian target of rapamycin (mTOR) pathway, BioCarta eukaryotic translation initiation factor 4 (EIF4) pathway, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in cancer. Interaction network analysis predicted genes participating in the regulatory connection. Highly differential expression of TRIM46, PCF11, BCL6, PTEN, and FUT1 genes was validated by quantitative real-time PCR in two cell line samples. Finally, BCL6 and Lewis Y antigen were validated at the protein level by immunohistochemistry in 103 paraffin-embedded ovarian cancer tissues. The identification of genes in response to FUT1 may provide a theoretical basis for the investigations of the molecular mechanism of ovarian cancer.

Wu YR, Qi HJ, Deng DF, et al.
MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer.
Tumour Biol. 2016; 37(9):12061-12070 [PubMed] Related Publications
Our study aimed to explore associations between microRNA-21 (miR-21) and PTEN/PI3K/AKT signaling pathway and, further, to elucidate the regulation of miR-21 on biological behaviors in human esophageal cancer cells. The expressions of miR-21, PTEN, PI3K, and AKT were detected in 89 esophageal cancer samples and 58 adjacent normal tissues respectively. The human esophageal cancer cells (TE11) were grouped as following: blank (TE11 cells without transfection), negative (TE11 cells with miR-21 negative inhibitor), and Inhibition-miR21 (TE11 cells with miR-21 inhibitor). Western blot was used for detection of PTEN, P13K, and AKT protein expressions, MTT method for cell proliferation, Transwell assay for cell migration and invasion, and flow cytometry for cell cycle and apoptosis. MiR-21, PI3K, and AKT have higher expressions, but PTEN has lower expression in esophageal cancer tissues compared with adjacent normal tissues. The esophageal cancer tissues with lymph node metastasis and poor differentiation showed significantly low positive rate of PTEN protein, but high positive rates of PI3K and AKT proteins. Compared with blank and negative groups, PTEN expression of TE11 cells in Inhibition-miR21 group was significantly up-regulated, but PI3K and AKT were down-regulated. Further, PTEN was a target gene of miR-21. Besides, compared with blank and negative groups, the proliferation, migration, and invasion of TE11 cells were less active in Inhibition-miR21 group. TE11 cells were significantly increased in the G0/G1 phase of cell cycles, but decreased in the S and G2/M phase in Inhibition-miR21 group. The TE11 cells exhibited significantly increased apoptosis rates. MiR-21 targets key proteins in PTEN/PI3K/AKT signal pathway, promoting proliferation, migration, invasion, and cell cycle, and inhibiting apoptosis of human esophageal cancer cells. It may serve as a novel therapeutic target in esophageal cancer.

Gao T, Mei Y, Sun H, et al.
The association of Phosphatase and tensin homolog (PTEN) deletion and prostate cancer risk: A meta-analysis.
Biomed Pharmacother. 2016; 83:114-121 [PubMed] Related Publications
OBJECTIVE: Phosphatase and tensin homolog (PTEN) deleted on chromosome 10, a tumor suppressor that negatively regulates the phosphoinositide-3-kinase(PI3K) which has been implicated in a number of human malignancies including prostate cancer. However the prognostic value of PTEN deletion in prostate cancer patient's diagnosis and the mechanism of PTEN deletion in prostate cancer development still remain unclear.
METHOD: A meta-analysis of 26 published studies including 8097 prostate cancer patients was performed.
RESULTS: Compared to PTEN normal patients, PTEN deletion patients showed a higher aggressive Gleason score(OR: 1.284, 95%CI=1.145-1.439) and pathological stage(OR: 1.628, 95%CI=1.270-2.087) which generally had a higher risk in prostate replace(HR: 1.738, 95%CI=1.264-2.390). Significant association between PTEN deletion and ERG rearrangements in prostate cancer development was also proved that compared to PTEN normal patients, patients with PTEN deletion showed a higher risk in ERG rearrangements(OR: 1.345, 95%CI=1.102-1.788).
CONCLUSION: This study indicated that patients with PTEN deletion were associated with higher pathological stage or Gleason score and a higher risk in prostate cancer replace potentially represent a novel clinically relevant event to identify individuals at increased risk for the occurrence, progression and prognosis of prostate cancer. Prostate cancer patients with PTEN deletion usually had a higher risk in ERG rearrangements than other patients may be a potential new area for identifying poor prognosis patients and selecting patients for targeted therapies which required confirmation through adequately designed prospective studies.

Shen H, Wang D, Li L, et al.
MiR-222 promotes drug-resistance of breast cancer cells to adriamycin via modulation of PTEN/Akt/FOXO1 pathway.
Gene. 2017; 596:110-118 [PubMed] Related Publications
BACKGROUND AND PURPOSE: Acquisition of resistance to adriamycin (ADR) is one of the most important clinical obstacles in the treatment of breast cancer, but the molecular mechanisms underlying sensitivity to ADR remain elusive. In our previous study, through miRNA microarray and experiments, we have emphasized that miR-222 could promote the ADR-resistance in breast cancer cells. The aim of this study was to explore the possible mechanism by which miR-222 affects sensitivity to ADR.
METHODS: Through pathway enrichment analyses for miR-222, we found that PTEN/Akt/FOXO1 signaling pathway may be of importance. RT-qPCR analyses and western blot assays confirmed the relationship between miR-222 expression and target genes. Immunofluorescence further visually displayed the location of FOXO1. When blocking PTEN/Akt/FOXO1 signaling pathway, we demonstrated the effects of miR-222-mediated ADR resistance by MTT and apoptosis assays.
RESULTS: RT-qPCR and Western blot results showed that miR-222 expression was negatively correlated with FOXO1 expression. In addition, the subcellular translocation of FOXO1 due to the altered expression of miR-222 was observed from immunofluorescence. Moreover, upregulation of miR-222 expression in MCF-7/S cells is associated with decreased PTEN expression levels and increased phospho-Akt (p-Akt) expression. Conversely in MCF-7/ADR cells, inhibition of miR-222 resulted in increased PTEN expression and decreased p-Akt expression. For further validation, results of the present study also demonstrated that PTEN/Akt/FOXO1 signaling was responsible for the ADR-resistance of breast cancer cells since LY294002, an inhibitor of Akt signaling, partially increased the sensitivity of MCF-7/S cells to ADR. More importantly, we postulated that high expression of miR-222 is closely related to poor overall survival by TCGA database validation.
CONCLUSIONS: Taken together, these data elucidated that miR-222 mediated ADR-resistance of breast cancer cells partly through regulation of PTEN/Akt/FOXO1 signaling pathway and inhibition of miR-222 may improve the prognosis of breast cancer patients.

Wang DD, Yang SJ, Chen X, et al.
miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27(kip1) pathway.
Tumour Biol. 2016; 37(11):15315-15324 [PubMed] Related Publications
The high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. Since miR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer through PTEN/Akt/p27 (kip1) pathway. Firstly, in vivo, we verified that miR-222 was upregulated in chemoresistant tissues after surgery compared with the paired preneoadjuvant samples of 21 breast cancer patients. Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to validate the pathway from the parental sensitive cell line (MCF-7/S). MCF-7/Adr and MCF-7/S were transfected with miR-222 mimics, miR-222 inhibitors, or their negative controls, respectively. The results showed that inhibition of miR-222 in MCF-7/Adr significantly increased the expressions of PTEN and p27 (kip1) and decreased phospho-Akt (p-Akt) both in mRNA and protein levels (p < 0.05) by using quantitative real-time PCR (qRT-PCR) and western blot. MTT and flow cytometry suggested that lower expressed miR-222 enhanced apoptosis and decreased the IC50 of MCF-7/Adr cells. Additionally, immunofluorescence demonstrated that the subcellular location of p27 (kip1) was dislocated resulting from the alteration of miR-222. Conversely, in MCF-7/S transfected with miR-222 mimics, upregulation of miR-222 is associated with decreasing PTEN and p27 (kip1) and increasing Akt accompanied by less apoptosis and higher IC50. Importantly, Adr resistance induced by miR-222 overexpression through PTEN/Akt/p27 was completely blocked by LY294002, an Akt inhibitor. Taken together, these data firstly elucidated that miR-222 could reduce the sensitivity of breast cancer cells to Adr through PTEN/Akt/p27 (kip1) signaling pathway, which provided a potential target to increase the sensitivity to Adr in breast cancer treatment and further improved the prognosis of breast cancer patients.

Lu E, Su J, Zeng W, Zhang C
Enhanced miR-9 promotes laryngocarcinoma cell survival via down-regulating PTEN.
Biomed Pharmacother. 2016; 84:608-613 [PubMed] Related Publications
MicroRNAs (miRNAs) play important roles in gene regulation during laryngocarcinoma. MiR-9 is a potential oncomiR, but its function in laryngocarcinoma is not known. The aim of this study is to investigate the roles of miR-9 in laryngocarcinoma. We found miR-9 expression was higher in laryngocarcinoma tissues compared with their normal controls, so did the laryngocarcinoma cells. Cellular function of miR-9 indicated that miR-9 restoration in laryngocarcinoma cells could promote cell proliferation and metastasis. Phosphatase and tensin homolog (PTEN) was predicted as a target gene of miR-9 and verified using luciferase reporter assay. PTEN expression was down-regulated in the laryngocarcinoma cells with miR-9 overexpression. We also found that miR-9 expression was negatively associated with PTEN expression in laryngocarcinoma tissues.

Yu M, Mu Y, Qi Y, et al.
Odontogenic ameloblast-associated protein (ODAM) inhibits human colorectal cancer growth by promoting PTEN elevation and inactivating PI3K/AKT signaling.
Biomed Pharmacother. 2016; 84:601-607 [PubMed] Related Publications
Odontogenic ameloblast-associated protein (ODAM), an acidic matricellular protein, has been implicated in several epithelial neoplasms. However, its biological functions and molecular mechanisms in cancer progression, particular colorectal carcinoma (CRC), remain unknown. Here we demonstrated that ODAM was significantly down-regulated in CRC tissues compared with their normal counterparts. Then, we established that ODAM expression level was closely correlated with CRC development and patient prognosis. The abnormal expression of ODAM dramatically affected CRC cell growth in vitro and in vivo. We further revealed that the inhibitory effects of ODAM on CRC cell growth were associated with PTEN elevation and PI3K/AKT signaling inactivation. Furthermore, we determined that silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing CRC cells. Our study suggests matricellular protein ODAM may serve as a novel prognostic marker and act as a CRC growth suppressor.

Ragos V, Fotiades PP, Tsiambas E, Peschos D
PTEN in laryngeal carcinomas.
J BUON. 2016 Jul-Aug; 21(4):1024-1025 [PubMed] Related Publications

Jin YY, Chen QJ, Xu K, et al.
Involvement of microRNA-141-3p in 5-fluorouracil and oxaliplatin chemo-resistance in esophageal cancer cells via regulation of PTEN.
Mol Cell Biochem. 2016; 422(1-2):161-170 [PubMed] Related Publications
microRNAs (miRNAs) act as a major regulator of acquired chemo-resistance in various types of cancer therapeutics. This study investigated the contribution of miRNAs in influencing multiple drug resistance in esophageal squamous cell carcinoma (ESCC). The sensitivity of four ESCC cell lines (EC109, EC9706, TE-1 and KYSE-150) to 5-fluorouracil (5-FU) and oxaliplatin (OX) was determined by MTT assay. A 5-FU and OX-resistant subline, EC9706R, was established by continuous exposure to stepwise increasing concentration of 5-FU and OX. Microarray technology was used to compare the differential expression of miRNAs between resistant cells and parental cells. Chemo-sensitivity assay was performed to evaluate drug response in EC9706R cells transfected with miRNA mimic or inhibitor. The direct targets of miRNA were identified by employing pathway analysis and then confirmed with luciferase assay. Sixty ESCC tissue samples and their paired adjacent normal tissues were collected to validate the expression of identified miRNA. Mouse models were further utilized to investigate the function of miRNA on acquired chemo-resistance. MicroRNA panel results indicated that a total of 12 miRNAs were differentially expressed and miR-141-3p was highly over expressed in resistant cells. Inhibition of miR-141-3p reversed acquired chemo-resistance in EC9706R cells by stimulating apoptosis. The expression of miR-141-3p was significantly increased in ESCC tissue samples compared to their matched distant normal tissues. In addition, the elevated miR-141-3p expression was found to be associated with ESCC differentiation status and TNM stage. Moreover, Phosphatase and tensin homolog (PTEN) was identified as direct target of miR-141-3p. Western blot exhibited altered protein levels of PTEN, Akt, and PI3k with miR-141-3p inhibitor. An inverse correlation between PTEN expression and miR-141-3p expression was also observed in tissue samples. EC9706R xenograft mouse model became sensitized to 5-FU and OX treatment following miR-141-3p inhibitor transfection in vivo. Our study demonstrated that miR-141-3p contributed to an acquired chemo-resistance through PTEN modulation both in vitro and in vivo.

Tong L, Luo Y, Wei T, et al.
KH-type splicing regulatory protein (KHSRP) contributes to tumorigenesis by promoting miR-26a maturation in small cell lung cancer.
Mol Cell Biochem. 2016; 422(1-2):61-74 [PubMed] Related Publications
KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein that has a role in tumorigenesis of small cell lung cancer. The KHSRP protein level was shown to be significantly increased in small cell lung cancer (SCLC) tumor tissues compared with normal lung tissues by immunohistochemical staining. Moreover, KHSRP protein levels were strongly associated with T stage in patients with SCLC. Using in vitro assays, we found that knockdown of the KHSRP gene inhibited cell proliferation and increased cell apoptosis but had no effect on cell migration and invasion. We also showed that down-regulation of the KHSRP gene suppressed tumor growth in vivo. Further analyses indicated that KHSRP was involved in miR-26a maturation and inhibited the expression of PTEN in SCLC cells. Taken together, these findings suggested that KHSRP plays an important role in SCLC tumorigenesis and could be a potential novel therapeutic target for SCLC treatment.

Tanaka R, Tomosugi M, Sakai T, Sowa Y
MEK Inhibitor Suppresses Expression of the miR-17-92 Cluster with G1-Phase Arrest in HT-29 Human Colon Cancer Cells and MIA PaCa-2 Pancreatic Cancer Cells.
Anticancer Res. 2016; 36(9):4537-43 [PubMed] Related Publications
BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs, and the deregulated expression of miRNAs is associated with tumor development. Among these, the miR-17-92 cluster, including six mature miRNAs, is known as an oncogenic miRNA cluster because expression of the miR-17-92 cluster is frequently elevated in a variety of malignant tumors.
MATERIALS AND METHODS: We investigated whether a mitogen-activated protein kinase kinase (MEK) inhibitor, PD0325901, suppresses expression of the miR-17-92 cluster in HT-29 human colon cancer cells and MIA PaCa-2 pancreatic cancer cells.
RESULTS: PD0325901 inhibited cell growth with G1-phase arrest and suppressed expression of the miR-17-92 cluster. Furthermore, phosphatase and tensin homolog (PTEN), which is a target molecule of the miR-17-92 cluster, was up-regulated by PD0325901. The exogenous expression of miR-17 slightly, but significantly reduced G1-phase arrest by PD0325901.
CONCLUSION: These results raise the possibility that a MEK inhibitor causes G1-phase arrest, at least partially, through suppression of the miR-17-92 cluster.

Teimourian S, Moghanloo E
Thwarting PTEN Expression by siRNA Augments HL-60 Cell Differentiation to Neutrophil-Like Cells by DMSO and ATRA.
DNA Cell Biol. 2016; 35(10):591-598 [PubMed] Related Publications
Abnormal cell differentiation, in particular suppression of terminal cell differentiation, exists in all tumors. Therapeutic interventions to restore terminal differentiation ("differentiation therapy") are a very attractive way to treat cancer, especially leukemia. A variety of chemicals stimulates differentiation of leukemic cells, such as dimethyl sulfoxide (DMSO) and all-trans retinoic acid (ATRA). Tumor suppressor genes have a vital role in the gateway to terminal cell differentiation. In this study, we inhibited PTEN tumor suppressor gene expression by siRNA to investigate the effect of potentiating cell survival and inhibiting apoptosis on HL-60 cell differentiation by DMSO and ATRA. Our results show that PTEN siRNA increases HL-60 cell differentiation in the presence of DMSO and ATRA. At the same time, the presence of siRNA hampers accumulation of apoptotic cells during incubation. Our study suggests that manipulation of PTEN could hold promise for enhancing efficacy of differentiation therapy of acute myelogenous leukemia.

Gui F, Hong Z, You Z, et al.
MiR-21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway.
Cell Biol Int. 2016; 40(12):1294-1302 [PubMed] Related Publications
MicroRNA-21 (miR-21) was reported to act as an oncogene during the development of many human tumors. However, little was revealed about the function of miR-21 in retinoblastoma (RB). In this study, we examined the expression of miR-21 in RB tissues and explored the relationship between miR-21 and phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-OH kinase (PI3K)/AKT signal. Quantitative real-time PCR (qRT-PCR) results showed that the level of miR-21 in RB tissues was higher than that in retinal normal tissues. In Weri-Rb-1 cells, miR-21 inhibitor suppressed the expression of miR-21 and cell viability, but improved cell apoptotic rates by modulating the levels of PDCD4, Bax, and Bcl-2. Meanwhile, miR-21 inhibitor suppressed cell migration and invasion via inhibiting the protein levels of MMP2 and MMP9 and significantly affected the expression of PTEN, PI3K, and p-AKT. Taken together, miR-21 inhibitor suppressed cell proliferation, migration, and invasion via the PTEN/PI3K/AKT signal. These findings revealed the molecular basis of miR-21 functioning in the progression of RB and provided a new means for cell therapy in RB.

Xiong J, Li Z, Zhang Y, et al.
PRL-3 promotes the peritoneal metastasis of gastric cancer through the PI3K/Akt signaling pathway by regulating PTEN.
Oncol Rep. 2016; 36(4):1819-28 [PubMed] Free Access to Full Article Related Publications
Peritoneal metastasis is the most frequent cause of death in patients with advanced gastric carcinoma (GC). The phosphatase of regenerating liver-3 (PRL-3) is recognized as an oncogene and plays an important role in GC peritoneal metastasis. However, the mechanism of how PRL-3 regulates GC invasion and metastasis is unknown. In the present study, we found that PRL-3 presented with high expression in GC with peritoneal metastasis, but phosphatase and tensin homologue (PTEN) was weakly expressed. The p-PTEN/PTEN ratio was also higher in GC with peritoneal metastasis than that in the normal gastric tissues. We also found the same phenomenon when comparing the gastric mucosa cell line with the GC cell lines. After constructing a wild-type and a mutant-type plasmid without enzyme activity and transfecting them into GC SGC7901 cells, we showed that only PRL-3 had enzyme activity to downregulate PTEN and cause PTEN phosphorylation. The results also showed that PRL-3 increased the expression levels of MMP-2/MMP-9 and promoted the migration and invasion of the SGC7901 cells. Knockdown of PRL-3 decreased the expression levels of MMP-2/MMP-9 significantly, which further inhibited the migration and invasion of the GC cells. PRL-3 also increased the expression ratio of p-Akt/Akt, which indicated that PRL-3 may mediate the PI3K/Akt pathway to promote GC metastasis. When we transfected the PTEN siRNA plasmid into the PRL-3 stable low expression GC cells, the expression of p-Akt, MMP-2 and MMP-9 was reversed. In conclusion, our results provide a bridge between PRL-3 and PTEN; PRL-3 decreased the expression of PTEN as well as increased the level of PTEN phosphorylation and inactivated it, consequently activating the PI3K/Akt signaling pathway, and upregulating MMP-2/MMP-9 expression to promote GC cell peritoneal metastasis.

Shi X, Gu HT, Lin SB, et al.
Abnormal expression of PTEN and PIK3CA in pemetrexed-resistant human pancreatic cancer cell line Patu8988.
Genet Mol Res. 2016; 15(3) [PubMed] Related Publications
The aim of this study was to investigate the expression of PTEN and PIK3CA in the pemetrexed-resistant human pancreatic cancer cell line Patu8988, and to evaluate their effects on the biological behavior of pancreatic cancer cells. PTEN and PIK3CA gene and protein expressions were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively, in a pemetrexed-resistant pancreatic cancer cell line and in the parent strain of the pancreatic cancer cells. The discrepancies between the two types of cell lines were detected by a transwell test. RT-PCR and western blot analyses revealed that PTEN and PIK3CA were overexpressed in the pemetrexed-resistant pancreatic cancer cell line. PTEN and PIK3CA were shown to be upregulated by 89 and 76% (western blot), respectively, in the pemetrexed-resistant cell line, compared to the normal pancreatic cancer cell line. The migratory and invasive abilities of the pemetrexed-resistant pancreatic cancer cell were significantly reduced compared to those of the parent strain (P < 0.05; transwell assay). Both PTEN and PIK3CA expression was abnormally enhanced in the pemetrexed-resistant cell line Patu8988; the co-existence of high levels of PTEN and PIK3CA in the pemetrexed-resistant pancreatic cancer line cells induced a significant decrease in their migratory and invasive capacities. This suggested that the mechanism of pemetrexed resistant may be affected by PTEN and PIK3CA, and that these may alter the biological behavior of cancer cells.

Shen H, Li L, Yang S, et al.
MicroRNA-29a contributes to drug-resistance of breast cancer cells to adriamycin through PTEN/AKT/GSK3β signaling pathway.
Gene. 2016; 593(1):84-90 [PubMed] Related Publications
PURPOSE: Acquisition of resistance to adriamycin (ADR) during the treatment of breast cancer is still a major clinical obstacle. MicroRNAs (miRNAs) are a class of short noncoding RNAs which associate with cancer chemoresistance through regulating gene expression by targeting mRNAs. Our previous microarray found that miR-29a may strongly confer the ADR resistance of breast cancer cells. Here, we aim to explore the possible mechanism by which miR-29a affects sensitivity to ADR.
METHODS: ADR-resistant MCF-7 breast cancer cell subline (MCF-7/ADR) was successfully established in vitro through a stepwise increase of ADR concentrations in the culture based on parental MCF-7 cell lines (MCF-7/S). We used TargetScan (a wide use of target prediction algorithms) in conjunction with pathway enrichment analyses to predict the mRNAs that were most likely to involve in miR-29a-mediated drug resistance in cancers. We confirmed the effects of miR-29a-mediated ADR resistance through MTT and apoptosis assays, and further investigated the activities of two target genes, PTEN and GSK3β, by RT-qPCR analyses and western blot assays.
RESULTS: The expression level of miR-29a in MCF-7/ADR cells was remarkablely higher than in MCF-7/S cells. Further MTT and apoptosis assays revealed that transfection of miR-29a inhibitors into MCF-7/ADR cells resulted in prominent reduction of the drug resistance, in contrast, transfection of miR-29a mimics into MCF-7/S cells obviously increased their drug resistance. Through pathway enrichment analyses for miR-29a, we found that PTEN/AKT/GSK3β signaling pathway may be of importance. RT-qPCR and Western blot results showed that downregulation of miR-29a expression in MCF-7/ADR cells increased PTEN expression levels, resulting in decreased phospho-Akt (p-Akt) and phospho-GSK3β (p-GSK3β) expression. Conversely, upregulation of miR-29a expression in MCF-7/S cells is associated with decreasing PTEN expression and increasing p-Akt and p-GSK3β expression.
CONCLUSIONS: PTEN and GSK3β are targeted by miR-29a, and miR-29a may contribute to ADR resistance through inhibition of the PTEN/AKT/GSK3β pathway in breast cancer cells. Thus, miR-29a may be a potential target for the patients who acquired ADR-resistance during the treatment of breast cancer.

Chen L, Zhang F, Sheng XG, et al.
MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells.
Oncol Rep. 2016; 36(4):2135-41 [PubMed] Related Publications
Ovarian cancer is a leading cause of malignant gynecological tumor-related mortality among women. The treatment of ovarian cancer patients continues to be challenging. MicroRNA‑106a (miR‑106a) is widely expressed in diverse human tumors. In the present study, we investigated the biological and pathological roles of miR-106a in ovarian cancers. We found that miR-106a expression was significantly increased in primary ovarian cancer tissues and ovarian cancer cells compared with the level in normal tissues. Ectopic expression of an miR-106a inhibitor attenuated ovarian cancer cell proliferation and invasion. miR-106a promoted the growth and invasion of SKOV3 cells by targeting phosphatase and tensin homolog (PTEN). Furthermore, the present study revealed that IL-6 inhibited miR-106a expression by activating STAT3. Tocilizumab, a humanized anti-human IL-6R antibody, that competitively inhibits IL-6/IL-6R signaling, did not inhibit the proliferation and invasion of SKOV3 cells. In conclusion, our studies revealed that miR-106a was significantly increased in the ovarian cancer tissues and cell lines. Downregulation of the expression of miR-106a inhibited cell growth and metastasis of ovarian cancer cells. Together, the present study suggests that miR‑106a acts as an oncogene in ovarian cancers.

Basra MA, Saher M, Athar MM, Raza MH
Breast Cancer in Pakistan a Critical Appraisal of the Situation Regarding Female Health and Where the Nation Stands?
Asian Pac J Cancer Prev. 2016; 17(7):3035-41 [PubMed] Related Publications
Breast cancer (BC) is the most common malignancy of women worldwide. In the past it was considered as disease of older middle aged women, but the incidence of BC in young females is growing in recent years concordant with studies in Pakistan. In this paper, we reviewed the mutant functions of tumor suppressor genes (BRCA1, BRCA2, p53, ATM and PTEN), epigenetic transformation and involvement of estrogen receptors in development of breast cancer. We further reviewed the current situation of BC in Pakistan that depicts a higher incidence in young females. According to SKMCH and RC data, age group 4549 years is more prone to BC with high rate of incidence 45.42%. A few studies explored the high expression of ER, PR and HER2/neu in Pakistani females. Moreover, presence of BRCA1 (c.1961dupA) mutation in Pakistani shows concordance with data in different areas of world. But we are unable to find an authentic study that can explore epigenetic based transformation of breast tumors in Pakistan. This area of research needs more attention to explore the complete picture of BC in Pakistan.

Lv X, Li J, Yang B
Clinical effects of miR-101 on prognosis of hepatocellular carcinoma and carcinogenic mechanism of anti-miR-101.
Oncol Rep. 2016; 36(4):2184-92 [PubMed] Related Publications
The aim of this study was to verify whether anti-miR-101 participates in the treatment of hepatocellular carcinoma (HCC) as a small-molecule antitumor agent, and to explore the effect on phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Patients who received consecutive hepatectomies were followed-up, and miR-101 expressions in their tumor and paracancerous tissues were detected. Correlation between miR-101 expression and clinical pathological factors and prognosis was studied. High‑throughput sequencing was used to detect the genetic and microRNA (miRNA) levels of tumor tissues. Expression of anti-miR-101 in different HCC cell lines was determined, and those of desired genes and proteins were detected by qRT-PCR and western blotting to obtain the target gene. miR-101 was significantly upregulated in HCC patients compared with that in paracancerous tissues. High miR-101 expression, vascular invasion, tumor size ≥7 cm and late pathological stage were the risk factors of recurrence-free survival rate. High miR-101 expression was the independent prognostic factor of total and recurrence-free survival rates. CXCL12, IL6R, FOXO3 and PTEN were screened as desired genes, and only PTEN was expressed significantly differently in three cell lines. miR-101 could bind 3'-UTR of WT-PTEN with reduced fluorescent intensity, suggesting that PTEN was the target gene. SMMC-7721, HepG2 and Huh7 were eligible cell lines for miR-101 studies. miR-101 was an applicable molecular marker of HCC. Anti-miR-101 regulated the transcription of PTEN and may promote cell proliferation, differentiation and apoptosis by regulating downstream genes with PTEN. The regulatory effects of anti-miR-101 on PTEN provide valuable evidence for finding novel miRNA drugs.

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