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miRNA Expression Analyses in Prostate Cancer Clinical Tissues

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

Hsa-miR-146a-5p modulates androgen-independent prostate cancer cells apoptosis by targeting ROCK1

Bin Xu^1,2, Yeqing Huang^1,2, Xiaobing Niu³

¹Department of Urology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.

|August 27, 2015

Abstract

Background:

MicroRNAs (miRNAs) have been demonstrated playing important roles in the procession of prostate cancer cells transformation from androgen-dependence to androgen-independence.

Methods:

We conducted the miRNA microarray and realtime PCR analyses in both androgen-dependent (ADPC) and androgen-independent prostate cancer (AIPC) tissues. We also explored the role of hsa-miR-146a-5p (miR-146a) in MSKCC prostate cancer clinical database. Moreover, the impact of miR-146a on prostate cancer cells apoptosis were detected by Hoechst staining and fluorescence-activated cell sorter (FACS). Its target is predicted by DIANA LAB online database and the result was assumed by western blotting and luciferase assay.

Results:

We demonstrated that miR-146a was down-regulated in AIPC tissues and cell lines compared to that in the ADPC tissues. In MSKCC data re-analyses, we found that miR-146a was underexpressed in metastatic prostate cancer tissues and those with Gleason score >8, moreover, low level of miR-146a represented a high biochemical relapse rate after radical prostatectomy. In the functional analyses, we transfected miR-146a mimics into CPRC cell lines and found miR-146a induced cells apoptosis. In mechanic analyses, we found that miR-146a inhibited the basal level of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) expression by targeting its 3'UTR and an inverse correlation of expression between miR-146a and ROCK1 was observed. Moreover, caspase 3 activity was stimulated by miR-146a overexpression.

Conclusion:

miR-146a has a critical role in the process of AIPC prostate cancer cells apoptosis through regulation of ROCK/Caspase 3 pathway. Targeting this pathway may be a promising therapeutic strategy for future personalized anti-cancer treatment.

Insights

MicroRNA-146a (miR-146a) is downregulated in aggressive prostate cancer, promoting cell survival. Restoring miR-146a induces apoptosis by inhibiting ROCK1 and activating Caspase 3, offering a potential therapeutic target.

Area of Science:

Molecular Oncology
Cancer Biology
Biochemistry

Background:

MicroRNAs (miRNAs) are crucial in prostate cancer progression, influencing the shift from androgen-dependent to androgen-independent states.
Understanding miRNA dysregulation is key to developing targeted therapies for advanced prostate cancer.

Purpose of the Study:

To investigate the role of hsa-miR-146a-5p (miR-146a) in prostate cancer, particularly in the transition to androgen independence.
To elucidate the molecular mechanisms by which miR-146a affects prostate cancer cell apoptosis.

Main Methods:

Microarray and real-time PCR analysis of miRNA expression in androgen-dependent (ADPC) and androgen-independent prostate cancer (AIPC) tissues.
Analysis of miR-146a expression in the MSKCC prostate cancer clinical database.
Functional assays including Hoechst staining, FACS, western blotting, and luciferase assays to assess miR-146a's impact on apoptosis and its targets.

Main Results:

miR-146a was significantly downregulated in AIPC tissues and cell lines compared to ADPC.
Low miR-146a expression correlated with metastatic disease, higher Gleason scores, and increased biochemical relapse rates.
Overexpression of miR-146a induced apoptosis in prostate cancer cells by inhibiting ROCK1 expression and activating Caspase 3.

Conclusions:

miR-146a plays a critical role in regulating apoptosis in androgen-independent prostate cancer cells via the ROCK1/Caspase 3 pathway.
Targeting the miR-146a/ROCK1/Caspase 3 pathway presents a promising therapeutic strategy for personalized prostate cancer treatment.

Read full analysis

Keywords:

ROCK1 apoptosis miR-146a prostate cancer

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