Chen Haiwen, Luo Qidong, Li Hongliang
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Tumour Biol. 2017 Mar;39(3):1010428317695941. doi: 10.1177/1010428317695941.
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.
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。
