Gene Summary

Gene:BTG2; BTG anti-proliferation factor 2
Aliases: PC3, APRO1, TIS21
Summary:The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein is involved in the regulation of the G1/S transition of the cell cycle. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:protein BTG2
Source:NCBIAccessed: 01 September, 2019


What does this gene/protein do?
Show (19)
Pathways:What pathways are this gene/protein implicaed in?
Show (1)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 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 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

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).

Latest Publications: BTG2 (cancer-related)

Örs Kumoğlu G, Döşkaya M, Gulce Iz S
The biomarker features of miR-145-3p determined via meta-analysis validated by qRT-PCR in metastatic cancer cell lines.
Gene. 2019; 710:341-353 [PubMed] Related Publications
MicroRNAs (miRNAs) play important roles in the cancer biology such as proliferation, differentiation, and apoptosis. The pivotal roles that miRNA expression plays, make them ideal candidates for detection of cancer progression as well as cancer metastasis. Especially for breast, lung and prostate cancer which are originated from soft tissues and prone to metastasis. Thus, the aim of this study is to evaluate the expression level of miR-145-3p which is a shared potential biomarker identified by meta-analysis of breast, prostate and lung cancer data sets. Six different data sets representative of three different cancer types were analyzed. These data sets are pooled together to have a master metamiRNA list while getting rid of the platform differentiations between them. As a result, 24 common differentially expressed miRNAs are determined in which miR-145-3p has the topmost rank. To mimic in vivo cancer microenvironment, hypoxia and serum deprivation were used to induce metastasis in breast (MCF-7, MDA-MB-231, MDA-MB-453), prostate (PC3, LNCaP, DU145), lung (A549, NCIH82,) cancer cell lines and noncancerous cell lines of the coresponding tissues (MCF10A, RWPE-1, MRC-5). miR-145-3p expression levels were determined by qRT-PCR. It has been shown that it is down regulated by the induction of metastasis in cancer cell lines while it is up regulated in normal cell lines to suppress the tumor formation. As a conclusion, as representing the same results in three different cancer cell types, miR-145-3p will be a promising biomarker to follow up its expression to detect cancer metastasis.

Hu J, Luo H, Xu Y, et al.
The Prognostic Significance of
Cancer Invest. 2019; 37(4-5):199-208 [PubMed] Related Publications
Prostate cancer (PCa) is the most common malignant tumor for men. But the mechanism is unclear.

Zhang X, Jin K, Luo JD, et al.
MicroRNA-107 inhibits proliferation of prostate cancer cells by targeting cyclin E1.
Neoplasma. 2019; 2019 [PubMed] Related Publications
Previous studies have reported that miR-107 could be utilized as a potential peripheral biomarker in prostate cancer (PCa). However, the specific functions of miR-107 in prostate cancer and its relevant mechanisms are still unknown. The aim of this research was to investigate the cellular functions of miR-107 in PCa and reveal the relevant mechanisms. MicroRNA tailing quantitative real-time PCR (qRT-PCR) was adopted to measure the expression of miR-107 in PCa cell line DU145 and PC3, as well as in normal prostate cell line RWPE-1. The miR-107 expression pattern in PCa tissues and paired peritumoral tissues were determined by Chromogenic In Situ Hybridization (CISH). Cell viability, colony formation, flow cytometry cell cycle and apoptosis, wound healing, and Transwell migration assays were performed to study the functions of miR-107 in PCa cells. Further, qRT-PCR, western blot analysis, and dual-luciferase reporter assays were conducted to verify the target of miR-107 in PCa. The results demonstrated that, miR-107 was down-regulated in PCa cells and tissues compared with normal prostate cells and peritumoral tissues, and over-expression of miR-107 suppressed the proliferation and induced G1/S arrest of PCa cells but had no effects on apoptosis or cell motility of PCa cells. MiR-107 was found to target cyclin E1 (CCNE1) in PCa cells by directly binding to its 3'-UTR. In conclusion, miR-107 could be a potential tumor suppressor in PCa, and the restoration of miR-107 might provide a new therapeutic option for PCa.

Pan D, Jia Z, Li W, Dou Z
The targeting of MTDH by miR‑145‑5p or miR‑145‑3p is associated with prognosis and regulates the growth and metastasis of prostate cancer cells.
Int J Oncol. 2019; 54(6):1955-1968 [PubMed] Free Access to Full Article Related Publications
Studies have rarely been conducted on the role of miRNAs in prostate cancer (PCa) cell progression by directly targeting MTDH, at least to the best of our knowledge. Thus, the present study aimed to identify miRNAs closely related with metadherin (MTDH) and to determine their roles in PCa. For this purpose, the expression levels of MTDH in PCa tissues and cell lines were examined by RT‑qPCR, immunohistochemistry and western blot analysis. By cell transfection, MTDH was either overexpressed in the normal prostate epithelial cell lines or silenced in tumor cell lines to determine cell viability, invasion and migration. Bioinformatics analysis, RT‑qPCR, western blot analysis, dual‑luciferase reporter assay and MTT assay were performed to identify direct the target of MTDH and to examine tumor cell viability. Rescue experiments using the PC‑3 and LNCaP cells were carried out by MTT assay, scratch wound assay, Transwell assay, RT‑qPCR and western blot analysis. Experiments were also conducted using 46 PCa human cancer and adjacent tissues, as wells as on 501 cases of PCa from the TCGA database. It was confirmed that the overexpression of MTDH was associated with a poor prognosis of patients. The overexpression of MTDH was found to promote the viability, invasion and migration of PCa cells. miR‑145‑5p and miR‑145‑3p identified from 16 miRNAs were found to be closely related to PCa and to be the targets of MTDH. Both these miRNAs were found to significantly suppress the growth and metastasis of PCa cells by negatively regulating the expression of MTDH. On the whole, the findings of this study demonstrate that MTDH functions as an oncogene in PCa and the inhibition of MTDH by miR‑145‑5p or miR‑145‑3p suppressed the growth and metastasis of PCa cells. The miR‑145‑5p/MTDH and miR‑145‑3p/MTDH pathways may thus become novel treatment targets for PCa.

Zhang J, Wang J, Luan T, et al.
Deubiquitinase USP9X regulates the invasion of prostate cancer cells by regulating the ERK pathway and mitochondrial dynamics.
Oncol Rep. 2019; 41(6):3292-3304 [PubMed] Free Access to Full Article Related Publications
The ubiquitin‑specific protease 9X (USP9X) is a conserved deubiquitinase that has been investigated in several types of human cancer. However, the clinical significance and the biological roles of USP9X in prostate cancer remain unexplored. In the present study, an investigation into the expression and clinical significance of USP9X in prostate cancer revealed that USP9X expression was downregulated in prostate cancer tissues compared with that in healthy tissues. In addition, decreased USP9X expression was associated with a higher Gleason score and local invasion. Depletion of USP9X in prostate cancer LNCaP and PC‑3 cells by small interfering RNA promoted cell invasion and migration. Furthermore, USP9X depletion upregulated matrix metalloproteinase 9 (MMP9) and the phosphorylation of dynamin‑related protein 1 (DRP1). Notably, a significant increase in phosphorylated extracellular signal‑regulated kinase (ERK), an upstream activator of MMP9 and DRP1, was observed. To investigate whether ERK activation was able to increase MMP9 protein levels and induce DRP1 phosphorylation, an ERK inhibitor was used, demonstrating that ERK‑mediated MMP9 production and change in mitochondrial function was critical for the biological function of USP9X in prostate cancer cells. In conclusion, the present study demonstrated that USP9X is downregulated in prostate cancer and functions as an inhibitor of tumor cell invasion, possibly through the regulation of the ERK signaling pathway.

Tiwari A, Mukherjee B, Hassan MK, et al.
Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion.
BMC Cancer. 2019; 19(1):346 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Prostate cancer is the most common form of cancer in males and accounts for high cancer related deaths. Therapeutic advancement in prostate cancer has not been able to reduce the mortality burden of prostate cancer, which warrants further research. FRG1 which affects angiogenesis and cell migration in Xenopus, can be a potential player in tumorigenesis. In this study, we investigated the role of FRG1 in prostate cancer progression.
METHODS: Immunohistochemistry was performed to determine FRG1 expression in patient samples. FRG1 expression perturbation was done to investigate the effect of FRG1 on cell proliferation, migration and invasion, in DU145, PC3 and LNCaP cells. To understand the mechanism, we checked expression of various cytokines and MMPs by q-RT PCR, signaling molecules by western blot, in FRG1 perturbation sets. Results were validated by use of pharmacological inhibitor and activator and, western blot.
RESULTS: In prostate cancer tissue, FRG1 levels were significantly reduced, compared to the uninvolved counterpart. FRG1 expression showed variable effect on PC3 and DU145 cell proliferation. FRG1 levels consistently affected cell migration and invasion, in both DU145 and PC3 cells. Ectopic expression of FRG1 led to significant reduction in cell migration and invasion in both DU145 and PC3 cells, reverse trends were observed with FRG1 knockdown. In androgen receptor positive cell line LNCaP, FRG1 doesn't affect any of the cell properties. FRG1 knockdown led to significantly enhanced expression of GM-CSF, MMP1, PDGFA and CXCL1, in PC3 cells and, in DU145, it led to higher expression of GM-CSF, MMP1 and PLGF. Interestingly, FRG1 knockdown in both the cell lines led to activation of p38 MAPK. Pharmacological activation of p38 MAPK led to increase in the expression of GM-CSF and PLGF in DU145 whereas in PC3 it led to enhanced expression of GM-CSF, MMP1 and CXCL1. On the other hand, inhibition of p38 MAPK led to reduction in the expression of above mentioned cytokines.
CONCLUSION: FRG1 expression is reduced in prostate adenocarcinoma tissue. FRG1 expression affects migration and invasion in AR negative prostate cancer cells through known MMPs and cytokines, which may be mediated primarily via p38 MAPK activation.

Savci-Heijink CD, Halfwerk H, Koster J, et al.
A specific gene expression signature for visceral organ metastasis in breast cancer.
BMC Cancer. 2019; 19(1):333 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Visceral organ metastasis is associated with poor survival outcomes in terms of metastasis free- and overall survival in breast carcinomas. Identification of a gene expression profile in tumours that selects a subpopulation of patients that is more likely to develop visceral organ metastases will help elucidate mechanisms for the development of distant metastases and could be of clinical value. With this study we aimed to determine genomic predictors that would help to distinguish breast cancer patients with more likelihood to develop visceral metastasis.
METHODS: Gene expression profiling data of 157 primary tumours from breast cancer patients who developed distant metastases were analyzed and differentially expressed genes between the group of tumours with visceral metastasis and the those without visceral metastases were identified. Published data were used to validate our findings. Multivariate logistic regression tests were applied to further investigate the association between the gene-expression-signature and clinical variables. Survival analyses were performed by the Kaplan-Meier method.
RESULTS: Fourteen differentially expressed genes (WDR6, CDYL, ATP6V0A4, CHAD, IDUA, MYL5, PREP, RTN4IP1, BTG2, TPRG1, ABHD14A, KIF18A, S100PBP and BEND3) were identified between the group of tumours with and without visceral metastatic disease. Five of these genes (CDYL, ATP6V0A4, PREP, RTN4IP1 and KIF18A) were up-regulated and the other genes were down-regulated. This gene expression signature was validated in the training and in the independent data set (p 2.13e- 08 and p 9.68e- 06, respectively). Multivariate analyses revealed that the 14-gene-expression-signature was associated with visceral metastatic disease (p 0.001, 95% CI 1.43-4.27), independent of other clinicopathologic features. This signature has been also found to be associated with survival status of the patients (p < .001).
CONCLUSION: We have identified an unique gene expression signature which is specific to visceral metastasis. This 14-gene-expression-signature may play a role in identifying the subgroup of patients with potential to develop visceral metastasis.

Wu Y, Hu L, Qin Z, Wang X
MicroRNA‑302a upregulation mediates chemo‑resistance in prostate cancer cells.
Mol Med Rep. 2019; 19(5):4433-4440 [PubMed] Related Publications
MicroRNAs (miRNAs) are post‑transcriptional regulators that mediate the initiation and progression of human cancer. Growing evidence suggests that deregulation of miRNA expression levels underlies chemo‑resistance. To investigate whether miRNA‑302a (miR‑302a) is involved in mediating chemo‑resistance to paclitaxel in prostate cancer, a series of in vitro analyses were performed in paclitaxel‑resistant prostate cancer PC‑3PR cells and non‑resistant prostate cancer PC‑3 cells. It was demonstrated that the expression of miR‑302a was upregulated in PC‑3PR cells. Notably, ectopic expression of miR‑302a also increased resistance to paclitaxel in wild‑type PC‑3 cells. By contrast, silencing of miR‑302a in PC‑3PR cells sensitized the cells to paclitaxel. Gene and protein expression analyses suggested that the miR‑302a target gene breast cancer resistance protein (BCRP) may mediate chemo‑resistance to paclitaxel in PC‑3PR cells. In conclusion, the data suggested that elevated miR‑302a levels, in part, mediate sensitivity to paclitaxel in prostate cancer through the aberrant regulation of its downstream targets, AOF2, BCRP and permeability glycoprotein 1. These data have implications for the development of novel therapeutics in prostate cancer that may improve sensitivity to chemotherapeutics.

Zhou M, Li W
Ent-Dihydrotucumanoic acid promotes apoptosis in PC-3 human prostate cancer cells.
Cell Mol Biol (Noisy-le-grand). 2019; 65(3):114-118 [PubMed] Related Publications
Prostate cancer (PC) has become a disease that pose a serious threat to men's health and life. In recent years, due to the changes of environment, lifestyle and other factors, the incidence of PC has been increasing rapidly in recent years, which is a serious threat to men's health. Ent-Dihydrotucumanoic Acid (DTA) is a compound isolated from Asteraceae of gymnosperms, which has many pharmacological effects. The effect of DTA on the growth of tumor cell line was studied by CCK-8 method, mitochondrial membrane potential and apoptosis were detected by flow cytometry, apoptosis-related genes were detected by Western blot assay, and the absorptivity of Caspase-3 and Caspase-9 was measured by spectrophotometer. It was found that DTA induces apoptosis of human prostate cancer cell line PC3 through mitochondrial pathway, thus preventing the development of prostate cancer. It lays the experimental foundation for the further development of DTA.

Sang Z, Jiang X, Guo L, Yin G
MicroRNA‑9 suppresses human prostate cancer cell viability, invasion and migration via modulation of mitogen‑activated protein kinase kinase kinase 3 expression.
Mol Med Rep. 2019; 19(5):4407-4418 [PubMed] Related Publications
MicroRNAs (miRs) are small non‑coding RNA molecules that regulate gene expression at the post‑transcriptional level. Aberrant expression of miR‑9 has been reported to be involved in the tumorigenesis and progression of various malignancies. However, its role in prostate cancer (PC) has not been completely clarified. In the present study, miR‑9 expression was examined in different PC cell lines, patient tissues and a mouse model. Cell Counting Kit‑8 and BrdU immunofluorescence assays were performed to assess the effect of miR‑9 on the viability of PC cells, while Transwell and wound‑healing assays were utilized to evaluate the migration and invasion of PC cells expressing miR‑9. Furthermore, a dual‑luciferase reporter assay was performed to verify whether mitogen‑activated protein kinase kinase kinase 3 (MEKK3) was a direct target of miR‑9. The results demonstrated significant downregulation of miR‑9 expression in different PC cell lines and 31 human PC tissues, as compared with that in a normal prostate cell line and adjacent normal tissues, respectively. By contrast, upregulation of MEKK3 was confirmed in human PC tissue samples, with its level inversely associated with miR‑9 expression. Overexpression of miR‑9 in six different PC cell lines (DU145, LNCaP, 22Rv1, PC‑3, C4‑2B and VCaP) reduced the cell viability and migration. Furthermore, it was demonstrated that the 3'‑untranslated region of MEKK3 was a target of miR‑9, and that MEKK3 overexpression prevented the inhibitory effects of miR‑9 on the viability, migration and invasion of PC cells. miR‑9 overexpressing tumor cells also exhibited growth delay in comparison with control tumor cells in vivo. Taken together, the current study findings provided novel insights into the underlying molecular mechanisms of PC oncogenesis, which may support the development of new therapeutic approaches for the treatment of PC.

Xiao L, Luo Y, Tai R, Zhang N
Estrogen receptor β suppresses inflammation and the progression of prostate cancer.
Mol Med Rep. 2019; 19(5):3555-3563 [PubMed] Free Access to Full Article Related Publications
Previous studies demonstrated that estrogen receptor β (ERβ) signaling alleviates systemic inflammation in animal models, and suggested that ERβ‑selective agonists may deactivate microglia and suppress T cell activity via downregulation of nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB). In the present study, the role of ERβ in lipopolysaccharide (LPS)‑induced inflammation and association with NF‑κB activity were investigated in PC‑3 and DU145 prostate cancer cell lines. Cells were treated with LPS to induce inflammation, and ELISA was performed to determine the expression levels of inflammatory cytokines, including tumor necrosis factor‑α (TNF‑α), monocyte chemoattractant protein 1 (MCP‑1), interleukin (IL)‑1β and IL‑6. MTT and Transwell assays, and Annexin V/propidium iodide staining were conducted to measure cell viability, apoptosis and migration, respectively. Protein expression was determined via western blot analysis. LPS‑induced inflammation resulted in elevated expression levels of TNF‑α, IL‑1β, MCP‑1 and IL‑6 compared with controls. ERβ overexpression significantly inhibited the LPS‑induced production of TNF‑α, IL‑1β, MCP‑1 and IL‑6. In addition, the results indicated that ERβ suppressed viability and migration, and induced apoptosis in prostate cancer cells, which was further demonstrated by altered expression of proliferating cell nuclear antigen, B‑cell lymphoma 2‑associated X protein, caspase‑3, E‑cadherin and matrix metalloproteinase‑2. These effects were reversed by treatment with the ERβ antagonist PHTPP or ERβ‑specific short interfering RNA. ERβ overexpression reduced the expression levels of p65 and phosphorylated NF‑κB inhibitor α (IκBα), but not total IκBα expression in LPS‑treated cells. In conclusion, ERβ suppressed the viability and migration of the PC‑3 and DU145 prostate cancer cell lines and induced apoptosis. Furthermore, it reduced inflammation and suppressed the activation of the NF‑κB pathway, suggesting that ERβ may serve roles as an anti‑inflammatory and anticancer agent in prostate cancer.

Yang C, Zhang W, Wang J, et al.
Effect of docetaxel on the regulation of proliferation and apoptosis of human prostate cancer cells.
Mol Med Rep. 2019; 19(5):3864-3870 [PubMed] Related Publications
Prostate cancer is a common type of malignancy. Given the complexity of prostate cancer and the pressing challenge of chemoresistance, the current study was conducted to investigate the effect of docetaxel (Doc) on androgen receptor (AR)‑dependent and AR‑independent prostate cancers cells. Subsequent experiments were designed to explore the mechanism underlying the Doc‑induced apoptosis. Three different human prostate cancer cell lines, namely PC‑3, LNCaP and DU‑145, were exposed to various concentrations of Doc. The cytotoxic effects of Doc were evaluated by an MTT assay, while apoptosis and cell cycle distribution were determined by flow cytometric analysis of cells stained with Annexin V‑FITC and propidium iodide. Western blot assay was also used to measure the protein levels of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated death promoter (Bad), total protein kinase B (Akt), phospho‑Akt and caspase‑3/9. Doc induced cytotoxicity in all three cell lines in a dose‑dependent manner. The half maximal inhibitory concentration values for the effect of Doc on PC‑3, DU‑145 and LNCaP cells were 3.72, 4.46 and 1.13 nM, respectively. Furthermore, the results indicated a significant difference in Doc sensitivity between AR‑dependent and AR‑independent prostate cancer cells. Evaluation of key gene expression at protein levels revealed a notable decrease in antiapoptotic Bcl‑2 and p‑Akt levels, along with a significant increase in pro‑apoptotic Bad, caspase‑3 and caspase‑9 levels. Therefore, Doc may induce cell apoptosis in prostate cancer via various pathways.

Gurung SK, Dana S, Mandal K, et al.
Downregulation of c-Myc and p21 expression and induction of S phase arrest by naphthalene diimide derivative in gastric adenocarcinoma cells.
Chem Biol Interact. 2019; 304:106-123 [PubMed] Related Publications
Naphthalene diimide (NDI) derivatives have been shown to exhibit promising antineoplastic properties. In the current study, we assessed the anticancer and anti-bacterial properties of di-substituted NDI derivative. The naphthalene-bis-hydrazimide, 1, negatively affected the cell viability of three cancer cell lines (AGS, HeLa and PC3) and induced S phase cell cycle arrest along with SubG0/G1 accumulation. Amongst three cell lines, gastric cancer cell line, AGS, showed the highest sensitivity towards the NDI derivative 1. Compound 1 induced extensive DNA double strand breaks causing p53 activation leading to transcription of p53 target gene p21 in AGS cells. Reduction in protein levels of p21 and BRCA1 suggested that 1 treated AGS cells underwent cell death due to accumulation of DNA damage as a result of impaired DNA damage repair. β-catenin downregulation and consequently decrease in levels of c-Myc may have led to 1 induced AGS cell proliferation inhibition.1 induced AGS cell S phase arrest was mediated through CylinA/CDK2 downregulation. The possible mechanisms involved in anticancer activity of 1 includes ROS upregulation, induction of DNA damage, disruption of mitochondrial membrane potential causing ATP depletion, inhibition of cell proliferation and downregulation of antiapoptotic factors ultimately leading to mitochondria mediated apoptosis. Further compound 1 also inhibited H. pylori proliferation as well as H. pylori induced morphological changes in AGS cells. These findings suggest that NDI derivative 1 exhibits two-pronged anticancer activity, one by directly inhibiting cancer cell growth and inducing apoptosis and the other by inhibiting H. pylori.

Leonardi DB, Anselmino N, Brandani JN, et al.
Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer.
Int J Mol Sci. 2019; 20(5) [PubMed] Free Access to Full Article Related Publications
Glucocorticoids are used during prostate cancer (PCa) treatment. However, they may also have the potential to drive castration resistant prostate cancer (CRPC) growth via the glucocorticoid receptor (GR). Given the association between inflammation and PCa, and the anti-inflammatory role of heme oxygenase 1 (HO-1), we aimed at identifying the molecular processes governed by the interaction between HO-1 and GR. PCa-derived cell lines were treated with Hemin, Dexamethasone (Dex), or both. We studied GR gene expression by RTqPCR, protein expression by Western Blot, transcriptional activity using reporter assays, and nuclear translocation by confocal microscopy. We also evaluated the expression of HO-1, FKBP51, and FKBP52 by Western Blot. Hemin pre-treatment reduced Dex-induced GR activity in PC3 cells. Protein levels of FKBP51, a cytoplasmic GR-binding immunophilin, were significantly increased in Hemin+Dex treated cells, possibly accounting for lower GR activity. We also evaluated these treatments in vivo using PC3 tumors growing as xenografts. We found non-significant differences in tumor growth among treatments. Immunohistochemistry analyses revealed strong nuclear GR staining in almost all groups. We did not observe HO-1 staining in tumor cells, but high HO-1 reactivity was detected in tumor infiltrating macrophages. Our results suggest an association and crossed modulation between HO-1 and GR pathways.

Luan X, Rahme K, Cong Z, et al.
Anisamide-targeted PEGylated gold nanoparticles designed to target prostate cancer mediate: Enhanced systemic exposure of siRNA, tumour growth suppression and a synergistic therapeutic response in combination with paclitaxel in mice.
Eur J Pharm Biopharm. 2019; 137:56-67 [PubMed] Related Publications
Small interfering RNA (siRNA) has recently illustrated therapeutic potential for malignant disorders. However, the clinical application of siRNA-based therapeutics is significantly retarded by the paucity of successful delivery systems. Recently, multifunctional gold nanoparticles (AuNPs) as non-viral delivery carriers have shown promise for transporting chemotherapeutics, proteins/peptides, and genes. In this study, AuNPs capped with polyethylenimine (PEI) and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of positively charged anisamide-targeted PEGylated AuNPs (namely Au-PEI-PEG-AA). The anisamide-targeted AuNPs effectively complexed siRNA via electrostatic interaction, and the resultant complex (Au

Camp NJ, Madsen MJ, Herranz J, et al.
Re-interpretation of PAM50 gene expression as quantitative tumor dimensions shows utility for clinical trials: application to prognosis and response to paclitaxel in breast cancer.
Breast Cancer Res Treat. 2019; 175(1):129-139 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor 'dimensions' were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying genetic susceptibilities and biological pathways. Here we explore the prognostic and predictive utility of these dimensions in a sub-study of GEICAM/9906, a Phase III randomized prospective clinical trial of paclitaxel in breast cancer.
METHODS: Tumor dimensions, PC1-PC5, were calculated using pre-defined coefficients. Univariable and multivariable Cox proportional hazards (PH) models for disease-free survival (DFS) were used to identify associations between quantitative dimensions and prognosis or response to the addition of paclitaxel. Results were illustrated using Kaplan-Meier curves.
RESULTS: Dimensions PC1 and PC5 were associated with DFS (Cox PH p = 6.7 [Formula: see text] 10
CONCLUSIONS: Our proof-of-concept application of quantitative dimensions illustrated novel findings and clinical utility beyond standard clinical-pathological characteristics and categorical intrinsic subtypes for prognosis and predicting chemotherapy response. Consideration of expression data as quantitative tumor dimensions offers new potential to identify clinically important patient subsets in clinical trials and advance precision medicine.

Cocchiola R, Lopreiato M, Guazzo R, et al.
The induction of Maspin expression by a glucosamine-derivative has an antiproliferative activity in prostate cancer cell lines.
Chem Biol Interact. 2019; 300:63-72 [PubMed] Related Publications
Mammary serine protease inhibitor or Maspin has been characterized as a class II tumor suppressor gene in several cancer types, among them prostate cancer (CaP). Androgen ablation is an effective therapy for CaP, but with short-term effectiveness, thus new therapeutic strategies are actively sought. The present study is aimed to explore the effects of a glucosamine derivative, 2-(N-Carbobenzyloxy)l-phenylalanylamido-2-deoxy-β-d-glucose (NCPA), on two CaP cell lines, PC3 and LNCaP. In particular we analyzed the impact of NCPA on Maspin production, cell viability and cell cycle progression and apoptosis/necrosis pathway activation in PC3 and LNCaP cell lines. NCPA is able to stimulate Maspin production in PC3 and not in LNCaP cell lines. NCPA blocks the PC3 cell cycle in G1 phase, by inhibiting Cyclin D1 production and induces the apoptosis, therefore interfering with aggressiveness of this androgen-insensitive cell line. Moreover, NCPA is able to induce the expression of Maspin in LNCaP cell line treated with androgen receptor inhibitor, Bicalutamide, and in turn to stimulate the apoptosis of these cells. These findings suggest that NCPA, stimulating the endogenous production of a tumor suppressor protein, could be useful in the design of new therapeutic strategies for treatment of CaP.

Pan Y, Zhang R, Chen H, et al.
Expression of Tripartite Motif-Containing Proteactiin 11 (TRIM11) is Associated with the Progression of Human Prostate Cancer and is Downregulated by MicroRNA-5193.
Med Sci Monit. 2019; 25:98-106 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Tripartite motif-containing protein 11 (TRIM11), encoded by the TRIM11 gene, has been studied in some human malignant tumors. MicroRNA-5193 (miRNA-5193) was predicted to target TRIM11, according to bioinformatics data from TargetScan. However, the roles of TRIM11 and miRNA-5193 in prostate cancer remain unknown. This study aimed to investigate the regulatory effects of miRNA-5193 on the expression of TRIM11 in prostate cancer tissues compared with adjacent normal prostate, and in human prostate cancer cell lines, PC3 and DU145 in vitro. MATERIAL AND METHODS Prostate tumor tissue and adjacent normal tissue from 137 patients with stage T1c (n=66), stage T2 (n=48), and stage T3 (n=23) prostate cancer were studied. Expression levels of the TRIM 11 protein and the TRIM11 gene in prostate cancer, normal prostate tissue, and human prostate cancer cell lines, PC3 and DU145, were measured by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Transfection with TRIM11 small interfering RNA (siRNA) resulted in gene knockdown. Transfection with a miR-5193 mimic resulted in overexpression of miR-5193. Proliferation and invasion assays were performed for PC3 and DU145 cells in vitro. RESULTS TRIM11 expression was upregulated in prostate cancer specimens compared with normal prostate tissue and was significantly correlated with reduced outcome. In human prostate cancer cell lines, PC3 and DU145, TRIM11 overexpression promoted cell proliferation. Upregulation of miR-5193 downregulated the expression of TRIM11. CONCLUSIONS TRIM11 was upregulated in prostate cancer tissue and was associated with reduced prognosis. TRIM11 expression increased cell proliferation in vitro and was downregulated by miR-5193.

Cultrara CN, Kozuch SD, Ramasundaram P, et al.
GRP78 modulates cell adhesion markers in prostate Cancer and multiple myeloma cell lines.
BMC Cancer. 2018; 18(1):1263 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Glucose regulated protein 78 (GRP78) is a resident chaperone of the endoplasmic reticulum and a master regulator of the unfolded protein response under physiological and pathological cell stress conditions. GRP78 is overexpressed in many cancers, regulating a variety of signaling pathways associated with tumor initiation, proliferation, adhesion and invasion which contributes to metastatic spread. GRP78 can also regulate cell survival and apoptotic pathways to alter responsiveness to anticancer drugs. Tumors that reside in or metastasize to the bone and bone marrow (BM) space can develop pro-survival signals through their direct adhesive interactions with stromal elements of this niche thereby resisting the cytotoxic effects of drug treatment. In this study, we report a direct correlation between GRP78 and the adhesion molecule N-cadherin (N-cad), known to play a critical role in the adhesive interactions of multiple myeloma and metastatic prostate cancer with the bone microenvironment.
METHODS: N-cad expression levels (transcription and protein) were evaluated upon siRNA mediated silencing of GRP78 in the MM.1S multiple myeloma and the PC3 metastatic prostate cancer cell lines. Furthermore, we evaluated the effects of GRP78 knockdown (KD) on epithelial-mesenchymal (EMT) transition markers, morphological changes and adhesion of PC3 cells.
RESULTS: GRP78 KD led to concomitant downregulation of N-cad in both tumors types. In PC3 cells, GRP78 KD significantly decreased E-cadherin (E-cad) expression likely associated with the induction in TGF-β1 expression. Furthermore, GRP78 KD also triggered drastic changes in PC3 cells morphology and decreased their adhesion to osteoblasts (OSB) dependent, in part, to the reduced N-cad expression.
CONCLUSION: This work implicates GRP78 as a modulator of cell adhesion markers in MM and PCa. Our results may have clinical implications underscoring GRP78 as a potential therapeutic target to reduce the adhesive nature of metastatic tumors to the bone niche.

Gao S, Zhao Z, Wu R, et al.
MiR-1 inhibits prostate cancer PC3 cells proliferation through the Akt/mTOR signaling pathway by binding to c-Met.
Biomed Pharmacother. 2019; 109:1406-1410 [PubMed] Related Publications
Prostate cancer (PC) is known as the most common cancer and is ranked second in cancer-related deaths in males. Accumulating evidence implicates microRNAs (miRNAs) may play key roles in tumorigenesis. We investigated the effects of microRNA-1 (miR-1) on the viability and proliferation of prostate cancer cells and the underlying mechanism. We first detected the miR-1 expression level in the PC cells by quantitative real-time PCR (qRT-PCR). The relation between the level of miR-1 and c-Met was investigated via luciferase reporter assay. Cell viability and proliferation were analyzed via MTT assay and flow cytometry in PC cells. Western blot was used for examining the related signaling pathway. MiR-1 expression was decreased and c-Met expression was increased in PC cells. Subsequently, we found that overexpression of miR-1 could inhibit viability and proliferation of PC cells functionally. Furthermore, the dual luciferase reporter assay results indicated that the c-Met is the target gene of miR-1. Western blot results indicated that this inhibition on the viability and proliferation of PC cells was via regulation of c-Met/AKT/mTOR signaling pathway. In conclusion, this study provides novel insight into the role of miR-1 in PC, and the results demonstrated that miR-1 could inhibit viability and proliferation of PC cells by targeting the c-Met/Akt/mTOR signaling pathway. MiR-1 might be a potential candidate for application in the treatment of PC.

Chen X, Chen Z, Zheng B, Tang W
Targeting NPRL2 to enhance the efficacy of Olaparib in castration-resistant prostate cancer.
Biochem Biophys Res Commun. 2019; 508(2):620-625 [PubMed] Related Publications
Castration-resistant prostate cancer (CRPC) lacks effective treatment, and studies have shown that PARPi inhibitors, such as Olaparib, are somewhat effective; however, the efficacy of Olaparib in CRPC still needs to be further improved. Nitrogen permease regulator-like 2 (NPRL2) is reported to be a tumor suppressor candidate gene and is closely related to the DNA repair pathway, which can affect the sensitivity of many chemotherapeutic drugs. However, there is no research on whether NPRL2 is associated with sensitivity to Olaparib. Hence, in the present study, we examined the NPRL2 expression levels in several PCa cell lines (LNCaP, PC3, and enzalutamide-resistant LNCaP, named LNPER) by Western blot. In addition, we investigated the role of NPRL2 expression and silencing in cell proliferation and in the regulation of ataxia telangiectasia mutated (ATM), which can mediate DNA repair and sensitivity to Olaparib. Furthermore, we performed in vitro and in vivo experiments to determine the mechanism of action of NPRL2 in adjusting Olaparib sensitivity. Our findings demonstrated that the NPRL2 expression level was upregulated in PCa cells, especially CRPC cells. NPRL2 overexpression promoted growth and resistance to Olaparib, and NPRL2 silencing inhibited proliferation, enhanced sensitivity to Olaparib, and increased CRRL2 expression in PCa cells. In addition, the Olaparib-induced growth delay in NPRL2-silenced PC3 tumors in mice correlated with ATM signaling downregulation, an apoptosis increase and migration/invasion suppression. Our results indicate that NPRL2 silencing enhances sensitivity to Olaparib treatment in CRPC and that NPRL2 may serve as a potential therapeutic target and predict resistance to Olaparib in CRPC.

Zheng XM, Zhang P, Liu MH, et al.
MicroRNA-30e inhibits adhesion, migration, invasion and cell cycle progression of prostate cancer cells via inhibition of the activation of the MAPK signaling pathway by downregulating CHRM3.
Int J Oncol. 2019; 54(2):443-454 [PubMed] Free Access to Full Article Related Publications
Prostate cancer (PCa) testing is currently based on measurement of serum prostate‑specific antigen levels and digital rectal examination, which are limited by a low predictive value and the adverse effects associated with overdiagnosis and overtreatment. Recent studies have reported that the abnormal expression of microRNAs (miRNAs) is associated with the mechanism underlying the development of PCa. Thus, the aim of the present study was to investigate the effects of miR‑30e and its target gene, M3 muscarinic acetylcholine receptor (CHRM3), on the adhesion, migration, invasion and cell cycle distribution of PCa cells via the mitogen‑activated protein kinase (MAPK) signaling pathway. The differentially expressed genes were screened in the Gene Expression Omnibus database from a gene expression microarray (GSE55945) of PCa. PCa tissues and adjacent tissues were collected from patients with PCa. The PC‑3 and DU145 human PCa cell lines were treated with activator, inhibitor and siRNAs. The effects of miR‑30e on cell adhesion, migration, invasion and cell cycle distribution with the involvement of CHRM3 and the MAPK signaling pathway were investigated. The bioinformatics results demonstrated that the CHRM3 gene and the MAKP signaling pathway were involved in the progression of PCa, and has‑miR‑30e was selected for further study. The levels of miR‑30e were significantly downregulated, while the levels of CHRM3 were obviously upregulated in PCa. CHRM3 was verified as a target gene of miR‑30e. Upregulation of miR‑30e and downregulation of CHRM3 decreased the levels of p‑P38, p‑extracellular signal‑regulated kinase, p‑c‑Jun N‑terminal kinase, p‑c‑fos and p‑c‑JUN, cell adhesion, migration and invasion ability, and the number of cells in the S phase, while they increased the number of cells in the G0 and G1 phases. The findings of the present study suggest that miR‑30e inhibited the adhesion, migration, invasion and cell cycle entry of PCa cells by suppressing the activation of the MAPK signaling pathway and inhibiting CHRM3 expression. Thus, miR‑30e may serve as a candidate target for the treatment of PCa.

Clemenceau A, Gaudreault N, Henry C, et al.
Tumor-based gene expression biomarkers to predict survival following curative intent resection for stage I lung adenocarcinoma.
PLoS One. 2018; 13(11):e0207513 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Prognostic biomarkers are needed in clinical setting to predict outcome after resection for early-stage lung adenocarcinoma. The goal of this study is to validate tumor-based single-gene expression biomarkers with demonstrated prognostic value in order to move them along the clinical translation pipeline.
METHODS: Prognostic genes were selected from the literature and the best candidates measured by quantitative real-time polymerase chain reaction (qPCR) in tumors of 233 patients with stage I adenocarcinoma. Significant prognostic genes were then validated in an independent set of 210 patients matching the first set in terms of histology, stage, and clinical data.
RESULTS: Eleven genes with demonstrated prognostic value were selected from the literature. Complementary analyses in public databases and our own microarray dataset led to the investigation of six genes associated with good (BTG2, SELENBP1 and NFIB) or poor outcome (RRM1, EZH2 and FOXM1). In the first set of patients, EZH2 and RRM1 were significantly associated with better survival on top of age, sex and pathological stage (EZH2 p = 3.2e-02, RRM1 p = 5.9e-04). The prognostic values of EZH2 and RRM1 were not replicated in the second set of patients. A trend was observed for both genes in the joint analyses (n = 443) with higher expression associated with worse outcome.
CONCLUSION: Adenocarcinoma-specific mRNA expression levels of EZH2 and RRM1 are associated with poor post-surgical survival in the first set of patients, but not replicated in a clinically and pathologically matched independent validation set. This study highlights challenges associated with clinical translation of prognostic biomarkers.

Doğan Şiğva ZÖ, Balci Okcanoğlu T, Biray Avci Ç, et al.
Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines.
Gene. 2019; 687:261-271 [PubMed] Related Publications
Paclitaxel, which isolated from Taxus brevifolia, is recently started to be used against prostate cancer treatment and it is a very effective compound against cancer. In this study, we aimed to test the synergistic effect of two plant active compounds (sulphoraphane (SFN) and silymarin (SILY)) and several endemic plant species from Turkey (such as Phlomis leucophracta, Rubia davisiana, Alkanna tinctoria), which are known to have anticarcinogenic effect on androgen-independent PC3 and DU145, and androgen-dependent VCaP prostate cancer cell lines, with paclitaxel on the expression of cell cycle signaling and apoptosis regulator genes. Herbal substances and endemic herbal extracts were combined with Paclitaxel drug. IC

Chen Q, Sun T, Wang F, et al.
Long Noncoding RNA IGF2AS is Acting as an Epigenetic Tumor Suppressor in Human Prostate Cancer.
Urology. 2019; 124:310.e1-310.e8 [PubMed] Related Publications
OBJECTIVE: To assess the expression profile and functional mechanism of long noncoding RNA (lncRNA) insulin growth factor 2 antisense (IGF2AS) in human prostate cancer (PCa).
METHODS: Quantitative reverse transcriptase-polymerase chain reaction was applied to assess IGF2AS expression in immortal PCa cell lines and in situ human PCa tumors. IGF2AS was overexpressed in VCaP and PC3 cells to assess its effect on PCa cell proliferation and invasion in vitro, and xenograft in vivo. The effect of IGF2AS overexpression on IGF2 was also assessed in PCa cells. Then, IGF2 was upregulated in IGF2AS-overexpressed PCa cells to assess the functional involvement of IGF2 in IGF2AS-mediated PCa cell development.
RESULTS: IGF2AS was downregulated in both PCa cell lines and human PCa tumors. In VCaP and PC3 cells, lentivirus-induced IGF2AS overexpression suppressed cancer cell proliferation and invasion in vitro, and xenograft development in vivo. IGF2 was downregulated by IGF2AS overexpression. Conversely, IGF2 upregulation revered the suppressing function of IGF2AS on PCa proliferation and invasion.
CONCLUSION: LncRNA IGF2AS is acting as an epigenetic tumor suppressor in human PCa, likely through inverse regulation on IGF2. IGF2AS/IGF2 axis may be a future therapeutic target for PCa treatment.

Lin H, Lin T, Lin J, et al.
Inhibition of miR-423-5p suppressed prostate cancer through targeting GRIM-19.
Gene. 2019; 688:93-97 [PubMed] Related Publications
OBJECTIVE: To determine the effect of miR-423-5p on the progression of prostate cancer (PC).
METHODS: miR-423-5p and GRIM-19 expressions were detected by qRT-PCR and western blot. PC cell proliferation was measured by MTT assay. PC cell apoptosis was detected by flow cytometry. Dual luciferase reporter assay was used to confirm the interaction between miR-423-5p and GRIM-19.
RESULTS: Compared with normal prostate tissues and prostate epithelial cell HPrEC, miR-423-5p was up-regulated in human PC tissues and PC3 cells, whereas GRIM-19 expression was decreased. Inhibition of miR-423-5p suppressed PC3 cell proliferation, promoted PC3 cell apoptosis, and decreased anti-apoptosis protein BCL-2 expression. GRIM-19 was a target of miR-423-5p, and GRIM-19 was negatively regulated by miR-423-5p in PC3 cells. In addition, miR-423-5p knockdown inhibited the proliferation and promoted the apoptosis of PC3 cells through GRIM-19. In vivo experiments showed that miR-423-5p inhibitor administration reduced tumor volume, down-regulated miR-423-5p and GRIM-19 expressions in PC tissues of nude mice.
CONCLUSION: Inhibition of miR-423-5p suppressed PC through targeting GRIM-19.

Li D, Liu J, Wang X, et al.
Biological Potential and Mechanism of Prodigiosin from
Int J Mol Sci. 2018; 19(11) [PubMed] Free Access to Full Article Related Publications
Tripyrrole molecules have received renewed attention due to reports of numerous biological activities, including antifungal, antibacterial, antiprotozoal, antimalarial, immunosuppressive, and anticancer activities. In a screen of bacterial strains with known toxicities to termites, a red pigment-producing strain, HDZK-BYSB107, was isolated from

Medina Enríquez MM, Félix AJ, Ciudad CJ, Noé V
Cancer immunotherapy using PolyPurine Reverse Hoogsteen hairpins targeting the PD-1/PD-L1 pathway in human tumor cells.
PLoS One. 2018; 13(11):e0206818 [PubMed] Free Access to Full Article Related Publications
Immunotherapy approaches stand out as innovative strategies to eradicate tumor cells. Among them, PD-1/PD-L1 immunotherapy is considered one of the most successful advances in the history of cancer immunotherapy. We used our technology of Polypurine reverse Hoogsteen hairpins (PPRHs) for silencing both genes with the aim to provoke the elimination of tumor cells by macrophages in co-culture experiments. Incubation of PPRHs against PD-1 and PD-L1 decreased the levels of mRNA and protein in THP-1 monocytes and PC3 prostate cancer cells, respectively. Viability of THP-1 cells and macrophages obtained by PMA-differentiation of THP-1 cells was not affected upon incubation with the different PPRHs. On the other hand, PC3 cell survival was partially decreased by PPRHs against PD-L1. The greatest effect in decreasing cell viability was obtained in macrophages/PC3 co-culture experiments by combining PPRHs against PD-1 and PD-L1. This effect was also observed in other cancer cell lines: HeLa, SKBR3 and to a minor extent in M21. Apoptosis was not detected when macrophages were treated with the different PPRHs. However, co-cultures of macrophages with the four cancer cell lines treated with PPRHs showed an increase in apoptosis. The order of fold-increase in apoptosis was HeLa > PC3 > SKBR3 > M21. This study demonstrates that PPRHs could be powerful pharmacological agents to use in immunotherapy approaches for the inhibition of PD-1 and PD-L1.

Probert C, Dottorini T, Speakman A, et al.
Communication of prostate cancer cells with bone cells via extracellular vesicle RNA; a potential mechanism of metastasis.
Oncogene. 2019; 38(10):1751-1763 [PubMed] Free Access to Full Article Related Publications
The role of extracellular vesicles (EVs) as vehicles for cell-to-cell communication between a tumour and its environment is a relatively new concept. The hypothesis that EVs may be critical in co-opting tissues by tumours to generate distant metastatic niches is particularly pertinent to prostate cancer (PCa), where metastatic-tropism to bone predominates over other tissue types. The potential role of EVs as a means of communication between PCa cells and cells of the bone stroma such as osteoblasts, is yet to be fully explored. In this study, we demonstrate that PCa cell EVs both enhance osteoblast viability and produce a significantly more supportive growth environment for PCa cells when grown in co-culture with EV-treated osteoblasts (p < 0.005). Characterisation of the RNA cargo of EVs produced by the bone-metastatic PCa cell line PC3, highlights the EV-RNA cargo is significantly enriched in genes relating to cell surface signalling, cell-cell interaction, and protein translation (p < 0.01). Using novel techniques to track RNA, we demonstrate the delivery of a set of PCa-RNAs to osteoblast via PCa-EVs and show the effect on osteoblast endogenous transcript abundance. Taken together, by using proof-of-concept studies we demonstrate for the first time the contribution of the RNA element of the PCa EV cargo, providing evidence to support PCa EV communication via RNA molecules as a potential novel route to mediate bone metastasis. We propose targeting PCa EVs could offer a potentially important preventative therapy for men at risk of metastatic PCa.

Wu S, Huang J, Hui K, et al.
2'‑Hydroxyflavanone inhibits epithelial‑mesenchymal transition, and cell migration and invasion via suppression of the Wnt/β‑catenin signaling pathway in prostate cancer.
Oncol Rep. 2018; 40(5):2836-2843 [PubMed] Related Publications
Despite the availability of a number of treatment options, certain cases of primary prostate cancer (PCa) will develop into metastatic PCa, in which epithelial‑mesenchymal transition (EMT) serves an important role. Recently, a natural flavonoid known as 2'‑hydroxyflavanone (2HF) exerts remarkable anticancer activity on various types of cancer. Our previous study demonstrated that 2HF could promote apoptosis and inhibit the proliferation of PCa cells, but whether 2HF is involved in the regulation of EMT, and cell migration and invasion in metastatic PCa remains unknown. The present study used two different metastatic PCa cell lines (PC‑3 and DU145) to investigate the effects of 2HF on EMT, and cell migration and invasion. The results demonstrated that 2HF could inhibit EMT, and cell migration and invasion through the Wnt/β‑catenin signaling pathway by suppressing GSK‑3β phosphorylation, β‑catenin expression and transactivation. In conclusion, the present study revealed a novel function of 2HF, which may be used to prevent or treat PCa metastasis.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. BTG2, Cancer Genetics Web: Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 01 September, 2019     Cancer Genetics Web, Established 1999