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微小RNA-590-3p通过靶向人前列腺癌细胞中的II型肌醇多磷酸4-磷酸酶促进细胞增殖和侵袭。

MicroRNA-590-3p promotes cell proliferation and invasion by targeting inositol polyphosphate 4-phosphatase type II in human prostate cancer cells.

作者信息

Chen Haiwen, Luo Qidong, Li Hongliang

机构信息

Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Tumour Biol. 2017 Mar;39(3):1010428317695941. doi: 10.1177/1010428317695941.

Abstract

Inositol polyphosphate 4-phosphatase type II emerges as a tumor suppressor in prostate cancer, and its loss of expression is associated with poor prognosis for prostate cancer. However, the mechanism of downregulation of inositol polyphosphate 4-phosphatase type II in prostate cancer development has not yet been fully clarified. In this study, microRNA-590-3p was found to be upregulated in both prostate cancer tissues and cell lines. Overexpression of microRNA-590-3p by microRNA-590-3p mimics promoted prostate cancer cell proliferation and invasion and accelerated the growth of xenografted tumors, while microRNA-590-3p inhibitors contributed to inhibition of cellular proliferation and invasion as well as tumor growth. A dual-luciferase reporter assay and expression analysis further confirmed that inositol polyphosphate 4-phosphatase type II was a direct target of microRNA-590-3p. Enforced expression of microRNA-590-3p led to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines. Overexpression of inositol polyphosphate 4-phosphatase type II could reduce microRNA-590-3p-induced cell proliferation and invasion as well as tumor growth, and decrease microRNA-590-3p-mediated upregulation of cyclin D1 and downregulation of p21 expression in prostate cancer cells. Taken together, our findings reveal that microRNA-590-3p is a potential onco-microRNA that participates in carcinogenesis of human prostate cancer by suppressing inositol polyphosphate 4-phosphatase type II expression and involving the Akt/FoxO3a pathway. MicroRNA-590-3p may represent a potential therapeutic target for prostate cancer patients.

摘要

II型肌醇多磷酸4-磷酸酶在前列腺癌中作为一种肿瘤抑制因子出现,其表达缺失与前列腺癌的不良预后相关。然而,II型肌醇多磷酸4-磷酸酶在前列腺癌发生发展过程中下调的机制尚未完全阐明。在本研究中,发现微小RNA-590-3p在前列腺癌组织和细胞系中均上调。通过微小RNA-590-3p模拟物过表达微小RNA-590-3p可促进前列腺癌细胞增殖和侵袭,并加速异种移植肿瘤的生长,而微小RNA-590-3p抑制剂则有助于抑制细胞增殖、侵袭以及肿瘤生长。双荧光素酶报告基因检测和表达分析进一步证实,II型肌醇多磷酸4-磷酸酶是微小RNA-590-3p的直接靶点。在前列腺癌细胞系中,强制表达微小RNA-590-3p导致II型肌醇多磷酸4-磷酸酶信使核糖核酸和蛋白质表达受到抑制,同时p-Akt、p-FoxO3a和细胞周期蛋白D1上调,p21表达下调。过表达II型肌醇多磷酸4-磷酸酶可减少微小RNA-590-3p诱导的细胞增殖、侵袭以及肿瘤生长,并降低微小RNA-590-3p介导的前列腺癌细胞中细胞周期蛋白D1上调和p21表达下调。综上所述,我们的研究结果表明微小RNA-590-3p是一种潜在的致癌微小RNA,它通过抑制II型肌醇多磷酸4-磷酸酶表达并涉及Akt/FoxO3a途径参与人类前列腺癌的致癌过程。微小RNA-590-3p可能是前列腺癌患者的一个潜在治疗靶点。

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