Related Experiment Video
Updated: Feb 11, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Attenuation of TGFBR2 expression and tumour progression in prostate cancer involve diverse hypoxia-regulated pathways
Hui Zhou1,2, Guanqing Wu1,2,3, Xueyou Ma1,2
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Background:
Dysregulation of transforming growth factor β (TGF-β) signaling and hypoxic microenvironment have respectively been reported to be involved in disease progression in malignancies of prostate. Emerging evidence indicates that downregulation of TGFBR2, a pivotal regulator of TGF-β signaling, may contribute to carcinogenesis and progression of prostate cancer (PCa). However, the biological function and regulatory mechanism of TGFBR2 in PCa remain poorly understood. In this study, we propose to investigate the crosstalk of hypoxia and TGF-β signaling and provide insight into the molecular mechanism underlying the regulatory pathways in PCa.
Methods:
Prostate cancer cell lines were cultured in hypoxia or normoxia to evaluate the effect of hypoxia on TGFBR2 expression. Methylation specific polymerase chain reaction (MSP) and demethylation agents was used to evaluate the methylation regulation of TGFBR2 promoter. Besides, silencing of EZH2 via specific siRNAs or chemical inhibitor was used to validate the regulatory effect of EZH2 on TGFBR2. Moreover, we conducted PCR, western blot, and luciferase assays which studied the relationship of miR-93 and TGFBR2 in PCa cell lines and specimens. We also detected the impacts of hypoxia on EZH2 and miR-93, and further examined the tumorigenic functions of miR-93 on proliferation and epithelial-mesenchymal transition via a series of experiments.
Results:
TGFBR2 expression was attenuated under hypoxia. Hypoxia-induced EZH2 promoted H3K27me3 which caused TGFBR2 promoter hypermethylation and contributed to its epigenetic silencing in PCa. Besides, miR-93 was significantly upregulated in PCa tissues and cell lines, and negatively correlated with the expression of TGFBR2. Ectopic expression of miR-93 promoted cell proliferation, migration and invasion in PCa, and its expression could also be induced by hypoxia. In addition, TGFBR2 was identified as a bona fide target of miR-93.
Conclusions:
Our findings elucidate diverse hypoxia-regulated pathways including EZH2-mediated hypermethylation and miR-93-induced silencing contribute to attenuation of TGFBR2 expression and promote cancer progression in prostate cancer.
Insights
Hypoxia downregulates TGFBR2 in prostate cancer via EZH2-mediated methylation and miR-93 induction, promoting tumor progression. Understanding these pathways is key for developing new prostate cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling
Background:
- Prostate cancer (PCa) progression is linked to dysregulated transforming growth factor β (TGF-β) signaling and hypoxia.
- Downregulation of TGFBR2, a key TGF-β pathway regulator, is implicated in PCa carcinogenesis, but its mechanisms remain unclear.
Purpose of the Study:
- To investigate the interplay between hypoxia and TGF-β signaling in PCa.
- To elucidate the molecular mechanisms regulating TGFBR2 expression under hypoxic conditions in prostate cancer.
Main Methods:
- Cultured PCa cell lines under hypoxia and normoxia.
- Utilized methylation-specific PCR, demethylation agents, and EZH2 inhibition to assess TGFBR2 promoter methylation.
- Performed PCR, Western blot, and luciferase assays to study miR-93 and TGFBR2 interactions.
- Assessed hypoxia's impact on EZH2 and miR-93, and miR-93's role in PCa cell proliferation and EMT.
Main Results:
- Hypoxia attenuated TGFBR2 expression in PCa cells.
- Hypoxia-induced EZH2 led to TGFBR2 promoter hypermethylation and epigenetic silencing.
- miR-93 was upregulated in PCa, negatively correlated with TGFBR2, and induced by hypoxia.
- Ectopic miR-93 expression promoted PCa cell proliferation, migration, and invasion; TGFBR2 is a direct target of miR-93.
Conclusions:
- Hypoxia-regulated EZH2-mediated hypermethylation and miR-93-induced silencing contribute to TGFBR2 downregulation in PCa.
- These pathways promote prostate cancer progression, highlighting potential therapeutic targets.
Related Concept Videos
02:24Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
02:24Regulation of Expression Occurs at Multiple Steps
02:42Transcription Attenuation in Prokaryotes
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:23Regulation of Expression at Multiple Steps
01:27Constitutive and Regulated Gene Expression