Zhang Wei, Liu Jianzhou, Qiu Jianxin, Fu Xiaoliang, Tang Qisheng, Yang Fan, Zhao Zhiguang, Wang He
Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Department of Urology, Central Hospital of Baoji, Baoji, Shaanxi 721008, P.R. China.
Oncol Rep. 2016 Dec;36(6):3707-3715. doi: 10.3892/or.2016.5141. Epub 2016 Oct 3.
MicroRNAs (miRNAs) have emerged as important regulators in cancer that are implicated in regulation of various cellular processes. miR-382 has been proposed as a tumor suppressor by several recent studies. However, the function of miR-382 in prostate cancer remains unknown. In this study, we aimed to investigate the potential function of miR-382 in prostate cancer. We found that miR-382 was significantly decreased in prostate cancer specimens and cancer cell lines. The overexpression of miR-382 in prostate cancer cells markedly inhibited cell proliferation, migration, and invasion. In contrast, miR-382 suppression exhibited an opposite effect. Target analysis predicted that chicken ovalbumin upstream promoter transcription factor II (COUP‑TFII) was a direct target of miR-382. This prediction was experimentally confirmed by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and western blot analysis. Our results further demonstrated that miR-382 inhibited the downstream genes of COUP‑TFII, including Snail and matrix metalloproteinase 2 (MMP2). Moreover, the restoration of COUP‑TFII expression significantly blocked the inhibitory effect of miR-382 on cell proliferation, migration, and invasion, and Snail expression. Taken together, this study suggests that miR-382 inhibits prostate cancer cell proliferation and metastasis through inhibiting COUP‑TFII, representing an important new mechanism for understanding prostate cancer pathogenesis and providing a novel therapeutic candidate target for prostate cancer therapy.
微小RNA（miRNA）已成为癌症中的重要调节因子，参与调控多种细胞过程。最近的几项研究提出miR-382是一种肿瘤抑制因子。然而，miR-382在前列腺癌中的功能尚不清楚。在本研究中，我们旨在探讨miR-382在前列腺癌中的潜在功能。我们发现miR-382在前列腺癌标本和癌细胞系中显著降低。在前列腺癌细胞中过表达miR-382可显著抑制细胞增殖、迁移和侵袭。相反，抑制miR-382则表现出相反的效果。靶点分析预测鸡卵清蛋白上游启动子转录因子II（COUP-TFII）是miR-382的直接靶点。双荧光素酶报告基因检测、实时定量聚合酶链反应和蛋白质印迹分析实验证实了这一预测。我们的结果进一步表明，miR-382抑制了COUP-TFII的下游基因，包括Snail和基质金属蛋白酶2（MMP2）。此外，恢复COUP-TFII的表达可显著阻断miR-382对细胞增殖、迁移、侵袭和Snail表达的抑制作用。综上所述，本研究表明miR-382通过抑制COUP-TFII来抑制前列腺癌细胞的增殖和转移，这代表了一种理解前列腺癌发病机制的重要新机制，并为前列腺癌治疗提供了一个新的治疗候选靶点。
