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微小RNA-429的下调通过靶向人前列腺癌细胞中的p27Kip1抑制细胞增殖。

Downregulation of microRNA-429 inhibits cell proliferation by targeting p27Kip1 in human prostate cancer cells.

作者信息

Ouyang Yongri, Gao Ping, Zhu Baoyi, Chen Xi, Lin Fang, Wang Xi, Wei Junxia, Zhang Huizhong

机构信息

Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

出版信息

Mol Med Rep. 2015 Feb;11(2):1435-41. doi: 10.3892/mmr.2014.2782. Epub 2014 Oct 27.

DOI:10.3892/mmr.2014.2782
PMID:25351256
Abstract

MicroRNAs (miRNAs) are closely associated with cell proliferation, invasion and metastasis in various types of cancer, including prostate cancer. In this study, the role of miR-429 in the regulation of cell proliferation was investigated in prostate cancer cells. miR-429 expression levels were measured in the IF11 and IA8 prostate cancer cell lines and normal prostate epithelial tissues by quantitative polymerase chain reaction. miR-429 mimics or an miR-429 inhibitor were then transfected into the human prostate cancer cell lines. MTT and fluorescence-activated cell sorting were used to detect the effect of miR-429 on cell proliferation. A luciferase reporter system was employed to verify the potential target of miR-429. The results revealed that miR-429 was significantly upregulated in the human prostate cancer cell lines, compared with the normal prostate epithelial tissue. Downregulation of miR-429 expression in IF11 and IA8 cells inhibited cell proliferation and arrested the cells in the G1 phase of the cell cycle. The luciferase assay demonstrated that p27Kip1 was a direct target of miR-429. Furthermore, overexpression of p27Kip1 was observed to partially rescue the proliferation‑promoting effect of miR-429 on IA8 cells. In conclusion, to the best of our knowledge this study was the first to show that miR-429 is involved in the oncogenesis of prostate cancer and thus may be a novel prognostic biomarker in prostate cancer.

摘要

微小RNA(miRNA)与包括前列腺癌在内的多种癌症的细胞增殖、侵袭和转移密切相关。在本研究中,我们探讨了miR-429在前列腺癌细胞增殖调控中的作用。通过定量聚合酶链反应检测了IF11和IA8前列腺癌细胞系以及正常前列腺上皮组织中miR-429的表达水平。然后将miR-429模拟物或miR-429抑制剂转染到人前列腺癌细胞系中。采用MTT法和荧光激活细胞分选术检测miR-429对细胞增殖的影响。利用荧光素酶报告系统验证miR-429的潜在靶点。结果显示,与正常前列腺上皮组织相比,人前列腺癌细胞系中miR-429显著上调。下调IF11和IA8细胞中miR-429的表达可抑制细胞增殖,并使细胞停滞于细胞周期的G1期。荧光素酶检测表明p27Kip1是miR-429的直接靶点。此外,观察到p27Kip1的过表达可部分挽救miR-429对IA8细胞的增殖促进作用。总之,据我们所知,本研究首次表明miR-429参与前列腺癌的肿瘤发生,因此可能是前列腺癌一种新的预后生物标志物。

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