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微小RNA-129-5p通过靶向ETS变异体1抑制前列腺癌增殖。

miR-129-5p inhibits prostate cancer proliferation via targeting ETV1.

作者信息

Gao Ge, Xiu Dianhui, Yang Bin, Sun Daju, Wei Xin, Ding Youpeng, Ma Yanan, Wang Zhixin

机构信息

Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

出版信息

Onco Targets Ther. 2019 May 9;12:3531-3544. doi: 10.2147/OTT.S183435. eCollection 2019.

DOI:10.2147/OTT.S183435
PMID:31190859
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6512784/
Abstract

BACKGROUND

Prostate cancer is one of the most commonly diagnosed diseases in males.

METHODS

RT-qPCR was used to detect miR-129-5p expression in tumor tissues and adjacent normal tissues from patients with prostate cancer. The cell proliferation assay and colony forming assay were used to study the role of miR-129-5p in mediating prostate cancer cell growth. Bioinformatic analysis and dual luciferase assay were performed to predict and confirm ETV1 as a target gene of miR-129-5p.

RESULTS

We found that miR-129-5p levels were decreased significantly in human prostate cancer tissues compared with matched normal tissues from patients with prostate cancer. Overexpression of miR-129-5p suppressed prostate cancer cell growth while antagonist of miR-129-5p promoted cell proliferation in immortal prostate cell line RWPE-1. In addition, elevation of miR-129-5p decreased ETV1 expression in prostate cancer cells while downregulation of miR-129-5p increased ETV1 expression in RWPE-1. Mechanistically, ETV1 is confirmed a direct target of miR-129-5p in prostate cancer cells. Through repression of ETV1 expression, miR-129-5p could inactivate YAP signaling in prostate cancer cells. In addition, overexpression of ETV1 attenuated miR-129-5p induced cell proliferation in prostate cancer cells. Correlation analysis further revealed that there was a negative correlation between miR-129-5p levels and ETV1 mRNA levels in tumor tissues from patients with prostate cancer.

CONCLUSION

Our results identified miR-129-5p as a tumor suppressor in prostate cancer via repression of ETV1.

摘要

背景

前列腺癌是男性中最常被诊断出的疾病之一。

方法

采用逆转录定量聚合酶链反应（RT-qPCR）检测前列腺癌患者肿瘤组织及癌旁正常组织中miR-129-5p的表达。运用细胞增殖实验和集落形成实验研究miR-129-5p在介导前列腺癌细胞生长中的作用。进行生物信息学分析和双荧光素酶实验以预测并证实ETS变异体1（ETV1）是miR-129-5p的靶基因。

结果

我们发现，与前列腺癌患者的配对正常组织相比，人前列腺癌组织中miR-129-5p水平显著降低。在永生化前列腺细胞系RWPE-1中，miR-129-5p的过表达抑制了前列腺癌细胞的生长，而miR-129-5p拮抗剂则促进了细胞增殖。此外，miR-129-5p的升高降低了前列腺癌细胞中ETV1的表达，而miR-129-5p的下调则增加了RWPE-1中ETV1的表达。从机制上来说，ETV1被证实在前列腺癌细胞中是miR-129-5p的直接靶标。通过抑制ETV1的表达，miR-129-5p可使前列腺癌细胞中的Yes相关蛋白（YAP）信号失活。此外，ETV1的过表达减弱了miR-129-5p诱导的前列腺癌细胞增殖。相关性分析进一步显示，前列腺癌患者肿瘤组织中miR-129-5p水平与ETV1 mRNA水平呈负相关。

结论

我们的研究结果表明，miR-129-5p通过抑制ETV1在前列腺癌中发挥肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c0/6512784/52b8671af47b/ott-12-3531Fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c0/6512784/52b8671af47b/ott-12-3531Fig8.jpg
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