Zhao Yongxiang, Yan Mingyu, Yun Ye, Zhang Jianguo, Zhang Ruimin, Li Yan, Wu Xiangming, Liu Qiang, Miao Wei, Jiang Haishan
Department of Urinary Surgery of The Fourth Hospital of Baotou, Baotou, Inner Mongolia, P.R. China.
The Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, Inner Mongolia, P.R. China.
Oncol Rep. 2017 Apr;37(4):2449-2458. doi: 10.3892/or.2017.5502. Epub 2017 Mar 13.
MicroRNAs (miRNAs) are strongly implicated in various cancers, including prostate cancer. Recently, microRNA-455-3p (miR-455-3p) has been shown to be aberrantly expressed in many tumor tissues, but its functions in tumorigenesis remain unknown. In this study, we investigated the role of miR-455-3p in prostate cancer. We found that miR-455-3p is markedly downregulated in prostate cancer cell lines and clinical tumor specimens. Gain-of-function and loss-of-function studies showed that miR-455-3p promotes prostate cancer cell growth both in vitro and in vivo. Bioinformatics analysis and Luciferase reporter assays demonstrated that miR-455-3p directly targets and suppresses eIF4E, the rate-limiting factor for cap-dependent translation, which plays important roles in the initiation and progression of prostate cancers. Further studies demonstrated that miR-455-3p inhibits cap-dependent translation and the proliferation of prostate cancer cells through targeting eIF4E. Taken together, our findings suggest that miR-455-3p functions as a tumor suppressor by directly targeting eIF4E in prostate carcinogenesis and may be used as a potential target for therapeutic intervention in prostate cancer.
微小RNA（miRNA）与包括前列腺癌在内的多种癌症密切相关。最近，微小RNA - 455 - 3p（miR - 455 - 3p）已被证明在许多肿瘤组织中表达异常，但其在肿瘤发生中的功能仍不清楚。在本研究中，我们调查了miR - 455 - 3p在前列腺癌中的作用。我们发现miR - 455 - 3p在前列腺癌细胞系和临床肿瘤标本中明显下调。功能获得和功能丧失研究表明，miR - 455 - 3p在体外和体内均促进前列腺癌细胞生长。生物信息学分析和荧光素酶报告基因检测表明，miR - 455 - 3p直接靶向并抑制eIF4E，即帽依赖性翻译的限速因子，其在前列腺癌的发生和发展中起重要作用。进一步研究表明，miR - 455 - 3p通过靶向eIF4E抑制帽依赖性翻译和前列腺癌细胞的增殖。综上所述，我们的研究结果表明，miR - 455 - 3p在前列腺癌发生过程中通过直接靶向eIF4E发挥肿瘤抑制作用，可能作为前列腺癌治疗干预的潜在靶点。
