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

miR-129-5p inhibits prostate cancer proliferation via targeting ETV1
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DOI:
10.2147/ott.s183435
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发表时间:
2019-01-01
影响因子:
4
通讯作者:
Wang, Zhixin
Wang, Zhixin
中科院分区:
医学3区
文献类型:
--
作者:
Gao, Ge;Xiu, Dianhui;Wang, Zhixin

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背景:前列腺癌是男性最常见的疾病之一。方法:采用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。通过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。通过生物信息学分析和双荧光素酶测定来预测和确认ETV1是miR-129-5p的靶基因。结果:我们发现,与前列腺癌患者匹配的正常组织相比,人前列腺癌组织中miR-129-5p水平明显降低。miR-129-5p过表达抑制前列腺癌细胞生长,而miR-129-5p拮抗剂促进永生前列腺细胞系RWPE-1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。在机制上,ETV1被证实是前列腺癌细胞中miR-129-5p的直接靶点。通过抑制ETV1的表达,miR-129-5p可以使前列腺癌细胞中的YAP信号失活。此外,ETV1过表达可减弱miR-129-5p在前列腺癌细胞中诱导的细胞增殖。相关分析进一步发现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在前列腺癌中发挥抑癌作用。
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.