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MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
Hypermethylation-mediated transcriptional repression of TMPRSS2 in androgen receptor-negative prostate cancer cells
Mingliang Chu1, Yunli Chang1, Naitao Wang2
1State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Abstract:
Prostate cancer is the most common type of cancer for men in the developed world. Androgen receptor (AR) is very important in prostate cancer progression. TMPRSS2 is an AR signaling downstream gene and closely related to prostate carcinogenesis. DNA methylation is a key mechanism to influence gene expression. Though previous reports have shown that AR signaling plays a critical role in the regulation of TMPRSS2 in prostate cancer, hardly any studies have examined whether the DNA methylation has been involved in the regulation of TMPRSS2. In the present study, we demonstrated that AR-negative prostate cancer (PCa) cells showed low expression levels and hypermethylation of TMPRSS2. In contrast, AR-positive PCa cells displayed high levels and hypomethylation of TMPRSS2. Treatment with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine reversed the low expression levels of TMPRSS2 in the AR-negative PCa cells. Additionally, we found that the level of DNA methyltransferases 1 (DNMT1) was high in AR-negative PCa cells, in which hypermethylation of TMPRSS2 and low expression level of TMPRSS2 were observed. Collectively, these data suggest that the high level of DNMT1 might be the mechanism for the hypermethylation-mediated transcriptional repression of TMPRSS2 in AR-negative PCa cells.
Insights
DNA methylation influences prostate cancer progression by regulating TMPRSS2 gene expression. High DNA methyltransferases 1 (DNMT1) levels in AR-negative prostate cancer cells lead to TMPRSS2 hypermethylation and repression.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Prostate cancer is a prevalent malignancy in men, with androgen receptor (AR) signaling driving its progression.
- TMPRSS2, an AR signaling downstream gene, is implicated in prostate carcinogenesis.
- DNA methylation is a critical epigenetic mechanism regulating gene expression.
Purpose of the Study:
- To investigate the role of DNA methylation in regulating TMPRSS2 expression in prostate cancer.
- To explore the relationship between androgen receptor status, TMPRSS2 methylation, and gene expression.
- To identify potential mechanisms underlying TMPRSS2 transcriptional repression in AR-negative prostate cancer cells.
Main Methods:
- Analysis of TMPRSS2 expression and DNA methylation levels in AR-positive and AR-negative prostate cancer cells.
- Treatment of AR-negative cells with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine.
- Assessment of DNA methyltransferases 1 (DNMT1) levels in relation to TMPRSS2 methylation and expression.
Main Results:
- AR-negative prostate cancer cells exhibited low TMPRSS2 expression and hypermethylation.
- AR-positive prostate cancer cells showed high TMPRSS2 expression and hypomethylation.
- Inhibition of DNA methylation with 5-Aza-2'-deoxycytidine restored TMPRSS2 expression in AR-negative cells.
- Elevated DNMT1 levels were observed in AR-negative cells with hypermethylated and lowly expressed TMPRSS2.
Conclusions:
- DNA methylation, potentially mediated by high DNMT1 levels, plays a significant role in TMPRSS2 transcriptional repression in AR-negative prostate cancer.
- These findings highlight a novel epigenetic mechanism regulating TMPRSS2 in prostate cancer progression.
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