miR-137-3p Modulates the Progression of Prostate Cancer by Regulating the JNK3/EZH2 Axis

Yachen Zang; Jin Zhu; Qin Li; Jian Tu; Xiaoqing Li; Rongkuan Hu; Dongrong Yang

doi:10.2147/OTT.S256161

miR-137-3p Modulates the Progression of Prostate Cancer by Regulating the JNK3/EZH2 Axis

Onco Targets Ther. 2020 Aug 10:13:7921-7932. doi: 10.2147/OTT.S256161. eCollection 2020.

Authors

Yachen Zang^#¹, Jin Zhu^#¹, Qin Li^#^{2

3}, Jian Tu⁴, Xiaoqing Li⁵, Rongkuan Hu³, Dongrong Yang¹

Affiliations

¹ Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China.
² School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
³ GenePharma-Deakin University Joint Laboratory of Aptamer Medicine, Suzhou 215123, People's Republic of China.
⁴ Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China.
⁵ Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou 215001, People's Republic of China.

^# Contributed equally.

Abstract

Background: Prostate cancer (PCa) is one of the most common cancers in men worldwide. Early detection of prostate cancer by prostate-specific antigen (PSA) screening still has limitations. The discovery of new candidates is urgent and can provide insights into the mechanism involved in prostate cancer tumorigenesis.

Methods: We conducted a cross-sectional study involving prostate cancer cell lines and clinical samples. qPCR and IHC were used to evaluate the expression of miR-137-3p/JNK3/EZH2. Furthermore, cell growth, migration, invasion, cell cycle and apoptosis were analyzed to describe the function of this axis. Moreover, xenograft models, pathology platforms and TCGA data were generated to confirm the role of the miR-137-3p/JNK3/EZH2 axis.

Results: In this study, we determined that miR-137-3p was significantly reduced in prostate cancer, and low expression of miR-137-3p was correlated with tumor stage . The overexpression of miR-137-3p suppressed cell proliferation, migration and invasion in prostate cancer by enhancing cell apoptosis. We also validated JNK3 (MAPK10) as a direct target gene of miR-137-3p. Down-regulation of JNK3 in prostate cancer also inhibited cell proliferation and invasion and promoted apoptosis. Moreover, JNK3 expression was up-regulated and negatively correlated with miR-137-3p in prostate cancer tissues. Furthermore, JNK3 modulated EZH2 expression, which is a key oncogene in prostate cancer. Survival data indicated that patients with high levels of JNK3 and EZH2 had a worse prognosis.

Conclusion: Collectively, the identification of miR-137-3p and the JNK3/EZH2 pathway might facilitate the development of biomarkers and therapeutic targets for prostate cancer.

Keywords: EZH2; MAPK10; biomarker; microRNA-137-3p; prostate cancer.

Grants and funding

This work was supported by grants from the Natural Science Foundation of Jiangsu Higher Education Institutions of China (18KJD320002) and National Natural Science Foundation of China (81802572) to Yachen Zang; the Suzhou Technology development program (ZXL2018171) to Rongkuan Hu; and the National Natural Science Foundation of China (81773221), National Natural Science Foundation of Jiangsu Province (BK20161222), and Suzhou Science and Technology Planned Projects (SYS201629, SS201857) to Jin Zhu.