Research IndicatorsGraph generated 11 March 2017 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 11 March, 2017 using data from PubMed, MeSH and CancerIndex
Specific Cancers (11)
Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
Numbers shown below represent number of publications held in OncomiRDB database for Oncogenic and Tumor-Suppressive MicroRNAs.
|Tissue||Target Gene(s)||Regulator(s)||MIR10A Function in Cancer||Effect|
-Nucleophosmin1 mutated acute myeloid leukaemia (1)
-acute myeloid leukemia (1)
-chronic myeloid leukemia (1)
|inhibit cell death (1)|
increase clonogenic capacity (1)
inhibit cell growth (1)
-pancreatic cancer (2)
|RARA (1)||promote cell invasion (2)|
promote metastasis (1)
|promote cell differentiation (2)|
-cervical cancer (1)
|DDX11 (1)||promote colony formation (1)|
promote cell migration (1)
promote cell invasion (1)
-breast cancer (1)
-glioblastoma stem cells (1)
Source: OncomiRDB Wang D. et al. Bioinformatics 2014, 30(15):2237-2238.
miRBase, University of Manchester
Annotated database entry including the location and sequence of the mature miRNA sequence.
miRCancer, East Carolina University
Search miRCancer for miR-10a associations with cancer and associated genes.
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: MIR10A (cancer-related)
Chemotherapies often induce drug-resistance in cancer cells and simultaneously stimulate proliferation and activation of Myeloid-Derived Suppressor Cells (MDSCs) to inhibit anti-tumor T cells, thus result in poor prognosis of patients with breast cancers. To date, the mechanism underlying the expansion of MDSCs in response to chemotherapies is poorly understood. In the present study, we used in vitro cell culture and in vivo animal studies to demonstrate that doxorubicin-resistant breast cancer cells secret significantly more prostaglandin E2 (PGE2) than their parental doxorubicin-sensitive cells. The secreted PGE2 can stimulate expansion and polymerization of MDSCs by directly target to its receptors, EP2/EP4, on the surface of MDSCs, which consequently triggers production of miR-10a through activating PKA signaling. More importantly, activated MDSCs can inhibit CD4(+)CD25(-) T cells as evidenced by reduced proliferation and IFN-γ release. In order to determine the molecular pathway that involves miR-10a mediated activation of MDSCs, biochemical and pharmacological studies were carried out. We found that miR-10a can activate AMPK signaling to promote expansion and activation of MDSCs. Thus, these results reveal, for the first time, a novel role of PGE2/miR-10a/AMPK signaling axis in chemotherapy-induced immune resistance, which might be targeted for treatment of chemotherapy resistant tumors.
Despite advances in the roles of long non-coding RNA (lncRNA) tumor suppressor candidate 7 (TUSC7) in cancer biology, which has been identified as a tumor suppressor by regulating cell proliferation, apoptosis, migration, invasion, cell cycle, and tumor growth, the function of TUSC7 in hepatocellular carcinoma (HCC) remains unknown. In this study, we observed that the expression of TUSC7 was immensely decreased in HCC. Clinically, the lower expression of TUSC7 predicted poorer survival and may be an independent risk factor for HCC patients. Moreover, TUSC7 inhibited cell metastasis, invasion, and epithelial-to-mesenchymal transformation (EMT) through competitively binding miR-10a. Furthermore, we found that TUSC7 could decrease the expression of Eph tyrosine kinase receptor A4 (EphA4), a downstream target of miR-10a as well as an EMT suppressor, through TUSC7-miR-10a-EphA4 axis. Taken together, we demonstrate that TUSC7 suppresses EMT through the TUSC7-miR-10a-EphA4 axis, which may be a potential target for therapeutic intervention in HCC.
Robertson NM, Toscano AE, LaMantia VE, et al.Unlocked Nucleic Acids for miRNA detection using two dimensional nano-graphene oxide.
Biosens Bioelectron. 2017; 89(Pt 1):551-557 [PubMed
] Related Publications
In this study we have used Unlocked Nucleic Acids (UNAs) to discriminate a breast cancer oncomiR from two other miRNAs in the same RNA family using two-dimensional graphene oxide nanoassemblies. Fluorescently labeled single stranded probe strands and graphene oxide nanoassemblies have been used to detect miR-10b and discriminate it from miR-10a, which differs by only a single nucleotide (12th base from the 5' end), and miR-10c, which differs by only two nucleotides (12th and 16th bases from the 5' end). We have determined the discrimination efficacy and detection capacity of a DNA probe with two inserted UNA monomers (UNA2), and compared it to the DNA probe with two purposefully inserted mutations (DNAM2) and full complementary sequence (DNAfull). We have observed that UNA2 is 50 times more powerful than DNAfull in discriminating miR-10b from miR-10c while generating an equally high fluorescence signal. This fluorescence signal was then further enhanced with the use of the highly specific endonuclease dsDNase for an enzymatic amplification step. The results demonstrate that the underutilized UNAs have enormous potential for miRNA detection and offer remarkable discrimination efficacy over single and double mismatches.
BACKGROUND MicroRNAs expression profiling of prostate cancer is becoming increasingly used due to its usefulness in diagnosis, staging, prognosis, and response to treatment. The aim of this study was to screen differentially expressed miRNAs in prostate cancer and analyze the functions and signal pathways of their target genes. MATERIAL AND METHODS High-throughput data of miRNAs were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 551 samples (52 normal and 499 prostate cancer cases) and 1046 miRNAs expression values were selected for further analysis. Differentially expressed miRNAs between normal and prostate cancer tissues were identified using SAMR. StarBase and TargetScan software were used to predict the miRNAs' target group and target genes, respectively. GO functional and KEGG pathway analysis was conducted on up/down-regulated expressed miRNA with DAVID. Finally, survival analysis was performed to evaluate the association of differently expressed miRNAs signature and overall survival of prostate cancer patients. RESULTS A total of 162 miRNAs were differentially expressed between normal and prostate cancer samples, including 128 up-regulated and 38 down-regulated ones; hsa-mir-153-2, hsa-mir-92a-1, and hsa-mir-182 (up-regulated); and hsa-mir-29a, hsa-mir-10a, and hsa-mir-221 (down-regulated) were identified as good biomarkers. In GO and KEGG analysis, target genes of down-regulated miRNAs were significantly enriched in positive ion combination and JAK-STAT pathway annotation, respectively; the ones with up-regulated miRNAs were significantly enriched in the function of plasma membrane and MARK signaling pathway annotation, respectively. Patients were categorized into low- or high-score groups according to their risk scores from each miRNA. The patients in the low-score group had better overall survival compared with those in high-score group. CONCLUSIONS The 6 differentially expressed miRNAs and their target genes were used to define important molecular targets that could serve as prognostic and predictive markers in the treatment of prostate cancer. Further research on the function of the target genes in the MAPK signal pathway could provide references for treatment of prostate cancer.
Yu Z, Li D, Ju XLCD4+ T cells from patients with acute myeloid leukemia inhibit the proliferation of bone marrow-derived mesenchymal stem cells by secretion of miR-10a.
J Cancer Res Clin Oncol. 2016; 142(4):733-40 [PubMed
] Related Publications
BACKGROUND: The abnormality of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been reported to contribute to the pathogenesis of acute myeloid leukemia (AML). T cell immunodeficiencies play important roles in the progression of leukemia. This study investigated the effect of CD4+ T cells from AML patients on the proliferation of BM-MSCs.
METHODS: The growth rate of BM-MSCs from AML patients and healthy donor was compared. CD4+ T cells were separated and identified from AML patients. Through co-culturing CD4+ T cells from AML patients and BM-MSCs from healthy, we detected the proliferation of BM-MSCs from healthy by MTT assay. qRT-PCR was performed to examine the expression of miR-10a. Luciferase reporter assay was used to analyze the regulation of miR-10a on the expression of BCL6.
RESULTS: Here, we observed that BM-MSC from AML patients grew slower than that from healthy. CD4+ T cells from AML patients inhibited the proliferation of BM-MSCs through secreting miR-10a. In addition, miR-10a was found to target BCL6 and regulated its expression in transcription and translation levels. Correlation analysis revealed that the level of miR-10a in serum of AML patients was negatively correlated with BCL6 in BM-MSC.
CONCLUSION: This study provides evidence that CD4+ T cells from AML patients suppress the proliferation of BM-MSCs via secreting miR-10a.
OBJECTIVE: Plasma miRNAs represent potential minimally invasive biomarkers to monitor and predict outcomes from chemotherapy. The primary goal of the current study-consisting of patients with recurrent, platinum-resistant ovarian cancer-was to identify the changes in circulating miRNA concentrations associated with decitabine followed by carboplatin chemotherapy treatment. A secondary goal was to associate clinical response with changes in circulating miRNA concentration.
METHODS: We measured miRNA concentrations in plasma samples from 14 patients with platinum-resistant, recurrent ovarian cancer enrolled in a phase II clinical trial that were treated with a low dose of the hypomethylating agent (HMA) decitabine for 5 days followed by carboplatin on day 8. The primary endpoint was to determine chemotherapy-associated changes in plasma miRNA concentrations. The secondary endpoint was to correlate miRNA changes with clinical response as measured by progression free survival (PFS).
RESULTS: Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29). Of these, 10 miRNAs (miR-193a-5p, miR-375, miR-339-3p, miR-340-5p, miR-532-3p, miR-133a-3p, miR-25-3p, miR-10a-5p, miR-616-5p, and miR-148b-5p) displayed fold changes in concentration ranging from -2.9 to 4 (p<0.05), in recurrent platinum resistant ovarian cancer patients, that were associated with response to decitabine followed by carboplatin chemotherapy. Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.
CONCLUSIONS: This is the first report demonstrating altered circulating miRNA concentrations following a combination platinum plus HMA chemotherapy regiment. In addition, circulating miR-148b-5p concentrations were associated with PFS and may represent a novel biomarker of therapeutic response, with this chemotherapy regimen, in women with recurrent, drug-resistant ovarian cancer.
Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. However, resistance to endocrine therapy leads to breast cancer relapse. The recent extension of adjuvant tamoxifen treatment up to 10 years actualizes the need for identifying biological markers that may be used to monitor predictors of treatment response. MicroRNAs are promising biomarkers that may fill the gap between preclinical knowledge and clinical observations regarding endocrine resistance. MicroRNAs regulate gene expression by posttranscriptional repression or degradation of mRNA, most often leading to gene silencing. MicroRNAs have been identified directly in the primary tumor, but also in the circulation of breast cancer patients. The few available studies investigating microRNA in patients suggest that seven microRNAs (miR-10a, miR-26, miR-30c, miR-126a, miR-210, miR-342 and miR-519a) play a role in tamoxifen resistance. Ingenuity Pathway Analysis (IPA) reveals that these seven microRNAs interact more readily with estrogen receptor (ER)-independent pathways than ER-related signaling pathways. Some of these pathways are targetable (e.g., PIK3CA), suggesting that microRNAs as biomarkers of endocrine resistance may have clinical value. Validation of the role of these candidate microRNAs in large prospective studies is warranted.
OBJECTIVES: Papillary thyroid cancer (PTC) is increasing in incidence. Fine needle aspiration is the gold standard for diagnosis, but results can be indeterminate. Identifying tissue and serum biomarkers, like microRNA, is therefore desirable. We sought to identify miRNA that is differentially expressed in the serum of patients with PTC.
METHODS: Serum miRNA was quantified in 31 female thyroidectomy patients: 13 with benign disease and 18 with PTC. qPCR results were compared for significant fold-changes in 175 miRNAs, against a pooled control.
RESULTS: 128 miRNA qualified for analysis. There were identifiable fold-changes in miRNA levels between benign and control, and between PTC and control. There were statistically significant fold changes in the level of four miRNAs between benign and PTC: hsa-miR-146a-5p and hsa-miR-199b-3p were down-regulated, while hsa-let7b-5p and hsa-miR-10a-5p were up-regulated.
CONCLUSIONS: MicroRNA is differentially expressed in the serum of patients with PTC. Serum miRNA has the potential to aid in thyroid cancer diagnosis.
MicroRNAs (miRNAs) are involved in human cancer including non-small cell lung cancer (NSCLC). In this study, we compared miRNA expression microarray of SPC-A-1sci (high metastatic) and SPC-A-1 (weakly metastatic) cells. We found that miRNA-10a was up-regulated in NSCLC compared with corresponding normal tissues. High expression of miR-10a was associated with tumor node metastasis and lymph node metastasis. Furthermore, overexpression of miR-10a promoted NSCLC cell proliferation, migration and invasion in vitro. We found that PTEN was a direct target of miR-10a in NSCLC. Also miR-10a activated the PTEN/AKT/ERK pathway. We suggest that miR-10a contributes to NSCLC by targeting PTEN.
Hu Y, Jin Y, Li X, et al.[Expression of microRNA-10a-5p in laryngeal epithelial premalignant lesions].
Zhonghua Bing Li Xue Za Zhi. 2015; 44(3):184-8 [PubMed
] Related Publications
OBJECTIVE: To investigate the expression of microRNA-10a-5p (miR-10a) in laryngeal epithelial premalignant lesions (LEPL) and to analyze the correlations of its dysregulation with clinicopathologic parameters of LEPL.
METHODS: According to the WHO classification (2005), 94 cases of LEPL were grouped into mild dysplasia (MID), moderate dysplasia (MOD), severe dysplasia (SD) and carcinoma in situ ( CIS). The expression of miR-10a in 94 cases of LEPL was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlated with the clinical and follow-up data of all LEPL patients.
RESULTS: miR-10a was down-regulated in LEPL with increasing grade of dysplasia. There was significantly statistical difference between low-risk ( MID + MOD) and high-risk ( SD + CIS) lesion groups (P = 0.03). The linear regression analysis showed that miR-10a was correlated with grade and gender of LEPL (P < 0.05).
CONCLUSIONS: Down regulation of miR-10a may be a useful molecular marker for grading of LEPL and diagnosis of early laryngeal cancer.
Zhi Y, Xie X, Wang R, et al.Serum level of miR-10-5p as a prognostic biomarker for acute myeloid leukemia.
Int J Hematol. 2015; 102(3):296-303 [PubMed
] Related Publications
MicroRNAs (miRNAs) are a type of small non-coding RNA molecule that play important roles in tumor initiation, chemotherapy response, promotion, and progression by negatively interfering with gene expression. The aim of the present study was to investigate the serum expression status and explore the prognostic significance of miR-10a-5p in acute myeloid leukemia (AML). The serum expression level of miR-10a-5p in de novo AML was significantly higher, compared with that in controls. The area under the receiver operator characteristic (ROC) curve was of 0.831 in the diagnostic value of miR-10a-5p. In the complete remission (CR) group, the serum expression level of miR-10a-5p was similar to that of healthy subjects and demonstrated a significant downtrend when compared to that on the day of diagnosis. Nevertheless, miR-10a-5p expression was found to significantly increase in cases of relapsed AML when compared individually to the CR population. On analysis of the association of miR-10a-5p expression with the clinical characteristics at diagnosis in AML patients, lower CR rates occurred more frequently in the high-expression group. In addition, high miR-10a-5p expression was associated with poorer overall survival (OS). These data suggest that miR-10a-5p may serve as a biomarker useful to improving the management of AML patients.
BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a.
METHODS: Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3.
RESULTS: The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect.
CONCLUSION: The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the microRNA.
Li MY, Hu XXMeta-analysis of microRNA expression profiling studies in human cervical cancer.
Med Oncol. 2015; 32(6):510 [PubMed
] Related Publications
Cervical cancer is one of the most common malignant tumors in women, and numerous studies have associated the disease with changes in microRNA (miRNA) expression. This meta-analysis aimed to consolidate and assess the results of these studies in order to identify potential miRNA biomarkers of cervical cancer. We systematically searched the literature for studies comparing miRNA expression between cervical cancer tissues and normal cervical tissues, and we meta-analyzed the result of 27 studies comprising 1,132 cancer samples and 943 normal samples. We used a vote-counting strategy that took into account total sample and mean fold-change, in order to comprehensively assess associations between certain miRNAs and cervical cancer occurrence and progression. The studies described 195 miRNAs that were significantly up-regulated and 96 microRNAs that were down-regulated in cervical cancer tissues (stage I-IV) relative to normal cervical tissues. Vote-counting analysis showed that up-regulation was most consistently reported for miR-20a and miR-21 (four studies), followed by miR-10a, miR-15b, miR-20b, miR-141, miR-200a, and miR-224 (three studies). Down-regulation was reported most consistently for miR-143 (seven studies), followed by miR-203 and miR-145 (six studies). Fourteen miRNA, respectively, showed a significantly correlated lymphatic node metastasis in eight studies. This meta-analysis has identified several miRNAs whose expression correlates reliably with cervical cancer. These should be probed in further studies to explore their potential as diagnostic biomarkers.
El-Halawany MS, Ismail HM, Zeeneldin AA, et al.Investigating the pretreatment miRNA expression patterns of advanced hepatocellular carcinoma patients in association with response to TACE treatment.
Biomed Res Int. 2015; 2015:649750 [PubMed
] Free Access to Full Article Related Publications
Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents-doxorubicin and cisplatin-is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.
Zhi YJ, Zhi F, Wang R, et al.[MicroRNA-10a expression in FAB different subtype of acute myeloid leukemia and its relationship with drug resistance].
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015; 23(1):29-33 [PubMed
] Related Publications
OBJECTIVE: This study was to investigate the expression of miR-10a in the different FAB subtype of acute myeloid leukemia (AML) and its relationship with drug resistance.
METHODS: Forty de novo patients with AML, 16 patients with non-malignant hematologic disease and three AML cell lines HL-60, U937 and HL-60/ADR were enrolled in this study, the MiR-10a expression in bone marrow mononuclear cells of above-mentioned patients and 3 AML cell lines was detected by TaqMan RT-PCR. The correlation of miR-10a with clinicopathological factors of AML patients was analyzed.
RESULTS: The miR-10a expression level in HL-60 cell line was higher than that in U937 cell line (P = 0.039). And its expression level in de novo AML patients was higher than that in patients with non-malignant hematologic disease (P < 0.01). FAB-AML-M3 patients exhibited higher expression of miR-10a than that in M1, M2 and M4 (P < 0.05); HL-60/ADR cell line showed higher miR-10a expression than that in HL-60 cell line (P < 0.01) . Except M3, the patients without CR (non-CR) after the first cycle of chemotherapy showed a higher level of miR-10a as compared with CR patients (P < 0.01).
CONCLUSION: The high expression of miR-10a may be closely related to over-proliferation of promyelocyte and drug resistance of acute myeloid leukemia cells, except M3.
Yan Y, Wang Q, Yan XL, et al.miR-10a controls glioma migration and invasion through regulating epithelial-mesenchymal transition via EphA8.
FEBS Lett. 2015; 589(6):756-65 [PubMed
] Related Publications
MicroRNAs (miRNAs) play a critical role in the development of cancers. However, the role of miRNAs in glioma is still poorly understood. In this study, we demonstrate that microRNA-10a (miR-10a) promotes cell migration and invasion by negatively regulating the expression of Eph tyrosine kinase receptor A8 (EphA8). Ectopic expression of EphA8 counteracts the promotion of migration and invasion induced by miR-10a. We further demonstrate that miR-10a and EphA8 regulate epithelial-mesenchymal transition (EMT) to affect cell migration and invasion. Collectively, we unveil a branch of the miR-10a/EphA8 pathway that regulates the progression of glioma.
Kuang L, Lv G, Wang B, et al.Overexpression of adenosine deaminase acting on RNA 1 in chordoma tissues is associated with chordoma pathogenesis by reducing miR‑125a and miR‑10a expression.
Mol Med Rep. 2015; 12(1):93-8 [PubMed
] Free Access to Full Article Related Publications
Chordoma is a rare, slow-growing primary malignant neoplasm of the axial skeleton, which arises from the remnants of the notochord. Emerging evidence suggests that microRNAs (miRs) are dysregulated in chordoma tissues and crucially involved in chordoma pathogenesis. In the present study, the expression of 11 candidate miRs were analyzed in chordoma tissues and miR-10a and miR-125a were found to be significantly downregulated compared with controls. Notably, the expression of the primary transcripts, pri-miR-125a and pri-miR-10a was unaltered, suggesting that disturbed microRNA expression may be induced by altered pri-miRNA processing. Previous studies have indicated that disturbed adenosine deaminase acting on RNA (ADAR) expression is able to alter mRNA and miRNA adenosine to inosine (A-to-I) levels associated with cancer pathogenesis. Therefore, the expression of ADAR1 and ADAR2 was analyzed in chordoma tissues. It was found that ADAR1 was significantly overexpressed, which was accompanied by enhanced pre-miR-10a and pri-miR-125a A-to-I editing. These findings suggest that ADAR2 overexpression causes enhanced pre-miR-10a and pri-miR-125a A-to-I editing, which alters mature miR-10a and miR-125a expression and may contribute to chordoma pathogenesis.
INTRODUCTION: MicroRNAs play an important role in many human malignancies; so far, their expression remains to be studied in upper urinary tract urothelial cancer (UUTUC).
MATERIALS AND METHODS: The expression of eleven microRNAs (miR-10a, miR-21, miR-96, miR-135, miR-141, miR-182, miR-200b, miR-205, miR-429, miR-520b, miR-1244) formerly shown to be upregulated in urothelial bladder cancer were studied in corresponding normal and cancerous tissue samples of patients undergoing nephroureterectomy for UUTUC. Upregulated microRNAs were then measured in serum samples of patients with UUTUC and patients with non-malignant urological diseases to evaluate their potential as non-invasive biomarkers for UUTUC.
RESULTS: MicroRNA expression allowed differentiation of normal and cancerous tissue: miR-21, miR-96, miR-135, miR-141, miR-182, miR-205, miR-429 and miR-520b were significantly overexpressed. Furthermore, miR-205 was upregulated in poorly differentiated UUTUC. The analysis of circulating RNA in serum demonstrated an increase of miR-141 in patients with UUTUC; receiver operator characteristic analysis demonstrated an area under the curve of 0.726 for miR-141 as a diagnostic biomarker. Furthermore, we observed lower levels of miR-10a and miR-135 in UUTUC patients.
CONCLUSIONS: MicroRNA expression is altered in UUTUC. The analysis of circulating miR-141 may be useful to identify patients with UUTUC.
Sun W, Ma Y, Chen P, Wang DMicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-β/Smad2/STAT3/STAT5 pathway.
Mol Med Rep. 2015; 11(5):3854-9 [PubMed
] Related Publications
Lung cancer is one of the primary causes of mortality worldwide and drug resistance is the key contributing factor which results in the failure of lung cancer chemotherapy. Previous studies have shown that microRNA (miR)‑10a was involved in the reversal of cisplatin (DDP) resistance in numerous types of tumors; however, the underlying mechanism of action of this remains to be fully elucidated. In the present study, miR‑10a silencing in human DDP‑resistant lung cancer A549/DDP cells was demonstrated to improve DDP sensitivity, apoptosis, intracellular rhodamine‑123 content as well as the expression and activity of caspase‑3/8. In addition, miR‑10a suppressed the cellular expression of P‑glycoprotein, multi‑drug resistance protein (MDR) 1, MDR‑associated protein 1, RhoE, B cell lymphoma‑2 and survivin in A549/DDP cells. Furthermore, miR‑10a silencing inhibited the secretion of transforming growth factor (TGF)‑β, phosphorylation of Sma‑ and Mad‑related protein (Smad)2, signal transducer and activator of transcription (STAT)3 and STAT5, the transcriptional activity of hypoxia‑inducible factor and eukaryotic translation initiation factor 4E in human lung cancer A549/DDP cell line. These results therefore indicated that miR‑10a may be a potential target for improving the effectiveness of lung cancer chemotherapy via regulation of the TGF‑β/Smad2/STAT3/STAT5 pathway.
Dip N, Reis ST, Abe DK, et al.Micro RNA expression and prognosis in low-grade non-invasive urothelial carcinoma.
Int Braz J Urol. 2014 Sep-Oct; 40(5):644-9 [PubMed
] Related Publications
PURPOSE: To analyze a possible correlation between a miRNA expression profile and important prognostic factors for pTa urothelial carcinomas (UC), including tumor size, multiplicity and episodes of recurrence.
MATERIALS AND METHODS: Thirty low-grade non-invasive pTa bladder UC from patients submitted to transurethral resection were studied, in a mean follow-up of 17.7 months. As controls, we used normal bladder tissue from five patients submitted to retropubic prostatectomy to treat benign prostatic hyperplasia. Extraction, cDNA and amplification were performed for 14 miRNAs (miR-100, -10a, -21, -205, -let7c, -143, -145, -221, -223, -15a, -16, -199a and -452) using specific kits, and RNU-43 and -48 were used as endogenous controls. Statistical tests were used to compare tumor size, multiplicity and episodes of recurrence with miRNAs expression profiles.
RESULTS: There was a marginal correlation between multiplicity and miR-let7c over-expression. For all others miRNA no correlation between their expression and prognostic factors was found.
CONCLUSION: We did not find differences for miRNAs expression profiles associated with prognostic factors in tumor group studied. The majority of miRNAs are down-regulated, except mir-10a, over-expressed in most of cases, seeming to have increased levels as tumor with more unfavorable prognostic factors. More studies are needed in order to find a miRNA profile able to provide prognosis in pTa UC to be used in clinical practice.
BACKGROUND: The major cancer related mortality is caused by metastasis and invasion. It is important to identify genes regulating metastasis and invasion in order to curtail metastatic spread of cancer cells.
METHODS: This study investigated the association between RUNX2 and miR-10a/miR-10b and the risk of breast cancer relapse. Expression levels of RUNX2 and miR-10a/b in 108 pairs of tumor and non-tumor tissue of breast cancer were assayed by quantitative PCR analysis and evaluated for their prognostic implications.
RESULTS: The median expression levels of RUNX2 and miR-10b in tumor tissue normalized using adjacent non-tumor tissue were significantly higher in relapsed patients than in relapse-free patients. Higher expression of these three genes were significantly correlated with the hazard ratio for breast cancer recurrence (RUNX2: 3.02, 95% CI = 1.50 ~ 6.07; miR-10a: 2.31, 95% CI = 1.00 ~ 5.32; miR-10b: 3.96, 95% CI = 1.21 ~ 12.98). The joint effect of higher expression of all three genes was associated with a hazard ratio of 12.37 (95% CI = 1.62 ~ 94.55) for relapse. In a breast cancer cell line, RUNX2 silencing reduced the expression of miR-10a/b and also impaired cell motility, while RUNX2 overexpression elicited opposite effects.
CONCLUSIONS: These findings indicate that higher expression of RUNX2 and miR-10a/b was associated with adverse outcome of breast cancer. Expression levels of RUNX2 and miR-10a/b individually or jointly are potential prognostic factors for predicting breast cancer recurrence. Data from in vitro studies support the notion that RUNX2 promoted cell motility by upregulating miR-10a/b.
Meyuhas O, Kahan TThe race to decipher the top secrets of TOP mRNAs.
Biochim Biophys Acta. 2015; 1849(7):801-11 [PubMed
] Related Publications
Cells encountering hostile growth conditions, like those residing in the middle of a newly developing solid tumor, conserve resources and energy by downregulating protein synthesis. One mechanism in this response is the translational repression of multiple mRNAs that encode components of the translational apparatus. This coordinated translational control is carried through a common cis-regulatory element, the 5' Terminal OligoPyrimidine motif (5'TOP), after which these mRNAs are referred to as TOP mRNAs. Subsequent to the initial structural and functional characterization of members of this family, the research of TOP mRNAs has progressed in three major directions: a) delineating the landscape of the family; b) establishing the pathways that transduce stress cues into selective translational repression; and c) attempting to decipher the most proximal trans-acting factor(s) and defining its mode of action--a repressor or activator. The present chapter critically reviews the development in these three avenues of research with a special emphasis on the two "top secrets" of the TOP mRNA family: the scope of its members and the identity of the proximal cellular regulator(s). This article is part of a Special Issue entitled: Translation and Cancer.
Zeng T, Li GMicroRNA‑10a enhances the metastatic potential of cervical cancer cells by targeting phosphatase and tensin homologue.
Mol Med Rep. 2014; 10(3):1377-82 [PubMed
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Cervical cancer is one of the leading causes of cancer‑related mortality worldwide. Previously, the upregulation of microRNA (miR)‑10a has been identified in human cervical cancer. The present study firstly demonstrated that miR‑10a was markedly upregulated in primary tumor tissues in patients with positive lymph node metastasis (LN+) compared with negative (LN‑) by quantitative polymerase chain reaction. miR‑10a mimics markedly enhanced cervical cancer cell migration and invasion abilities, and accordingly the miR‑10a inhibitor suppressed those functions. Furthermore, these data suggested that the phosphatase and tensin homologue (PTEN) was inhibited by miR‑10a through an miR‑10a binding site within the 3'‑untranslated region of PTEN at the posttranscriptional level, and that miR‑10a mimics promoted nuclear translocation of β‑catenin. Therefore, it was concluded that the overexpression of miR‑10a contributes to metastasis in cervical cancer by targeting PTEN. miR‑10a may therefore be used clinically as a molecular marker for patients with cervical cancer lymph node metastasis.
Tezcan G, Tunca B, Bekar A, et al.microRNA expression pattern modulates temozolomide response in GBM tumors with cancer stem cells.
Cell Mol Neurobiol. 2014; 34(5):679-92 [PubMed
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Temozolomide (TMZ) is widely used to treat glioblastoma multiforme (GBM). Although the MGMT gene methylation status is postulated to correlate with TMZ response, some patients with a methylated MGMT gene still do not benefit from TMZ therapy. Cancer stem cells (CSCs) may be one of the causes of therapeutic resistance, but the molecular mechanism underlying this resistance is unclear. microRNA (miRNA) deregulation has been recognized as another chemoresistance modulating mechanism. Thus, we aimed to evaluate the miRNA expression patterns associated with chemoresistance that is dependent on the CSC status in GBM tumors to identify therapeutic biomarkers. CSCs were identified in 5 of 20 patients' tumor tissues using magnetic separation. CSC (+) tumors displayed a significant induction of CpG island methylation in the MGMT gene promoter (p = 0.009). Using real-time reverse transcription polymerase chain reaction (qRT-PCR), 9 miRNAs related to GBM (mir-181b, miR-153, miR-137, miR-145, miR-10a, miR-10b, let-7d, miR-9, and miR-455-3p), which are associated with cell cycle and invasion was analyzed in tumor samples. Low miR-181b and high miR-455-3p expression levels were detected (p = 0.053, p = 0.004; respectively) in CSC (+) tumors. Analysis revealed a significant correlation between miR-455-3p expression and Smad2 protein levels as analyzed by immunohistochemistry in CSC (+) tumors (p = 0.002). Thus, miR-455-3p may be involved in TMZ resistance in MGMT methylated CSC (+) GBM patients. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for GBM treatment and new directions for the development of anticancer drugs.
Medina-Villaamil V, Martínez-Breijo S, Portela-Pereira P, et al.Circulating MicroRNAs in blood of patients with prostate cancer.
Actas Urol Esp. 2014; 38(10):633-9 [PubMed
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INTRODUCTION: MicroRNAs (miRNAs) are small regulatory RNAs that do not code for proteins. Detection of circulating tumor cells (CTC) would provide diagnostic and prognostic information in prostate tumors (PT). Thus, miRNAs could constitute a promising new class of biomarkers for CTC detection.
OBJECTIVES: To analyze circulating microRNAs in whole blood as non-invasive markers in patients with localized prostate cancer and healthy individuals.
MATERIAL AND METHODS: A preliminary study including a population of 40 patients with mean age of 71 years and mean PSA of 18, 9 ng/ml (range). Regarding the risk group (RG): 33.3% had low risk, 30% intermediate risk and 36.7% high risk. A previous in silico study identified 92 candidates and was followed by another in vivo to verify the findings of the former using array technology by real-time PCR.
RESULTS: Statistical analysis of the results revealed 10 microRNAs candidates with statistically significant differential expression between the different risk groups and healthy controls: hsa-miR-337-3p, hsa-miR-330-3p, hsa-miR-339-3p, hsa-miR-124, hsa-miR-218, hsa-miR-128, hsa-miR-10a, hsa-miR-199b-5p, hsa-miR-200b and hsa-miR-15b.
CONCLUSIONS: Our data suggest that circulating microRNAs can act as biomarkers to identify risk groups in CaP.
Recurrent breast cancer occurring after the initial treatment is associated with poor outcome. A bimodal relapse pattern after surgery for primary tumor has been described with peaks of early and late recurrence occurring at about 2 and 5 years, respectively. Although several clinical and pathological features have been used to discriminate between low- and high-risk patients, the identification of molecular biomarkers with prognostic value remains an unmet need in the current management of breast cancer. Using microarray-based technology, we have performed a microRNA expression analysis in 71 primary breast tumors from patients that either remained disease-free at 5 years post-surgery (group A) or developed early (group B) or late (group C) recurrence. Unsupervised hierarchical clustering of microRNA expression data segregated tumors in two groups, mainly corresponding to patients with early recurrence and those with no recurrence. Microarray data analysis and RT-qPCR validation led to the identification of a set of 5 microRNAs (the 5-miRNA signature) differentially expressed between these two groups: miR-149, miR-10a, miR-20b, miR-30a-3p and miR-342-5p. All five microRNAs were down-regulated in tumors from patients with early recurrence. We show here that the 5-miRNA signature defines a high-risk group of patients with shorter relapse-free survival and has predictive value to discriminate non-relapsing versus early-relapsing patients (AUC = 0.993, p-value<0.05). Network analysis based on miRNA-target interactions curated by public databases suggests that down-regulation of the 5-miRNA signature in the subset of early-relapsing tumors would result in an overall increased proliferative and angiogenic capacity. In summary, we have identified a set of recurrence-related microRNAs with potential prognostic value to identify patients who will likely develop metastasis early after primary breast surgery.
Nucleophosmin-mutated acute myeloid leukemia (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Because miR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs could predict chemotherapy response in AML. We found that high baseline miR-10 family expression in 54 untreated cytogenetically heterogeneous AML patients was associated with achieving CR. However, when we included NPM1 mutation status in the multivariable model, there was a significant interaction effect between miR-10a-5p expression and NPM1 mutation status. Similar results were observed when using a second cohort of 183 cytogenetically normal older (age ≥ 60 years) AML patients. Loss- and gain-of-function experiments using miR-10a-5p in cell lines and primary blasts did not demonstrate any effect in apoptosis or cell proliferation at baseline or after chemotherapy. These data support a bystander role for the miR-10 family in NPM1mut-AML.
BACKGROUND: MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes. Their deregulations occur commonly in gastric cancer (GC). Although DNA methylation constitutes an important mechanism for microRNA deregulation in cancer, this field largely remains unexplored.
METHODOLOGY/PRINCIPAL FINDINGS: Total RNA was extracted from the tissues of 100 patients with GC and four gastric cancer cell lines. The expression levels of miR-10a were determined by real-time PCR with specific TaqMan probes. Moreover, a functional analysis of miR-10a in regulating cell proliferation, migration and invasion was performed. Subsequently, quantitative methylation-specific PCR (qMSP) was used to detect the DNA methylation status in the CpG islands upstream of miR-10a. In this study, we found that the expression of miR-10a in GC cells was lower than that in normal cells, which was due to the hypermethylation of the CpG islands upstream of miR-10a. We also validated the slightly lower expression of miR-10a in GC tissues than their adjacent non-neoplastic tissues in 100 GC patients and confirmed the hypermethylation of CpG islands upstream of miR-10a in some patients. Furthermore, re-introduction of miR-10a into GC cells was able to inhibit cell proliferation, migration and invasion. Bioinformatic and immunoblot analysis indicated that the tumor suppressor roles of miR-10a in GC cells were possibly through targeting HOXA1.
CONCLUSIONS/SIGNIFICANCE: Our data indicate that miR-10a acts as a tumor suppressor in GC cells and is partially silenced by DNA hypermethylation in GC, suggesting that miR-10a may serve as a potential diagnostic or therapeutic target of GC.
Segersten U, Spector Y, Goren Y, et al.The role of microRNA profiling in prognosticating progression in Ta and T1 urinary bladder cancer.
Urol Oncol. 2014; 32(5):613-8 [PubMed
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OBJECTIVE: To analyze microRNA profile in Ta and T1 urinary bladder cancers in combination and separately and to relate this to the risk of later developing higher-stage disease.
MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded samples of 44 Ta and 42 T1 bladder cancers representing cases with and without stage progression during follow-up were collected and microRNA expression levels were measured by microarray analysis.
RESULTS: In a comparison between the progressors and controls, in the Ta/T1 group, miR-10a-5p and miR-31-5p were differentially expressed. miR-10a-5p was also correlated to time to progression (P = 0.00012). In the subgroup analysis, 3 microRNAs, miR-10a-5p, miR-31-5p, and miR-130a-3p, were differentially expressed among Ta tumors and had a fold change of more than 1.5 (P<0.038). The comparison concerning microRNA expression between the progressors and controls in category T1 cancers revealed no significant differences.
CONCLUSIONS: Profiling revealed that certain microRNAs predicted the risk of developing higher-stage disease among patients with Ta cancers. Lower miR-10a-5p expression in Ta progressing tumors indicates that this microRNA could be important for later malignant potential among this group of patients.
Visani M, de Biase D, Marucci G, et al.Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III.
Mol Oncol. 2014; 8(2):417-30 [PubMed
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Several biomarkers have been proposed as useful parameters to better specify the prognosis or to delineate new target therapy strategies for glioblastoma patients. MicroRNAs could represent putative target molecules, considering their role in tumorigenesis, cancer progression and their specific tissue expression. Although several studies have tried to identify microRNA signature for glioblastoma, a microRNA profile is still far from being well-defined. In this work the expression of 19 microRNAs (miR-7, miR-9, miR-9∗, miR-10a, miR-10b, miR-17, miR-20a, miR-21, miR-26a, miR-27a, miR-31, miR-34a, miR-101, miR-137, miR-182, miR-221, miR-222, miR-330, miR-519d) was evaluated in sixty formalin-fixed and paraffin-embedded glioblastoma samples using a locked nucleic acid real-time PCR. Moreover, a comparison of miRNA expressions was performed between primary brain neoplasias of different grades (grades IV-I). The analysis of 14 validated miRNA expression in the 60 glioblastomas, using three different non-neoplastic references as controls, revealed a putative miRNA signature: mir-10b and miR-21 were up-regulated, while miR-7, miR-31, miR-101, miR-137, miR-222 and miR-330 were down-regulated in glioblastomas. Comparing miRNA expression between glioblastoma group and gliomas of grades I-III, 3 miRNAs (miR-10b, mir-34a and miR-101) showed different regulation statuses between high-grade and low-grade tumors. miR-10b was up-regulated in high grade and significantly down-regulated in low-grade gliomas, suggesting that could be a candidate for a GBM target therapy. This study provides further data for the identification of a miRNA profile for glioblastoma and suggests that different-grade neoplasia could be characterized by different expression of specific miRNAs.