MicroRNA-1291 mediates cell proliferation and tumorigenesis by downregulating MED1 in prostate cancer
MicroRNA-1291 mediates cell proliferation and tumorigenesis by downregulating MED1 in prostate cancer
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DOI：
10.3892/ol.2019.9980
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发表时间：
2019-03-01
期刊：
影响因子：
2.9
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Cai, Qi;Zhao, An;Zhang, Wei
miRNAs是参与调节肿瘤发展的重要因子。miR-1291被发现在许多肿瘤中具有调节作用，但其在前列腺癌（PCa）中的作用仍不清楚。本研究通过检测miR-1291在前列腺癌中的表达，探讨其在前列腺癌发生发展中的作用及其机制。采用逆转录-定量聚合酶链反应（RT-qPCR）检测miR-1291在PCa组织和细胞系中的表达，并与正常组织和细胞系进行比较。应用miR-1291模拟物和抑制剂以在PCa细胞中过表达或抑制miR-1291的水平。MTT法检测细胞增殖能力，流式细胞仪检测细胞周期分布。通过蛋白质印迹分析和荧光素酶测定鉴定miR-1291的潜在靶标。建立PCa异种移植模型，探讨miR-1291在PCa中的作用。结果显示，miR-1291在PCa组织中的表达水平明显低于癌旁正常组织。在PCa衍生的细胞中，miR-1291的表达水平也下调。过表达miR-1291可明显抑制DU-145细胞增殖，并诱导细胞周期由G 0/G1期向S期转变。而抑制miR-1291则促进LNCaP细胞生长，并促进细胞周期向S期和G2/M期转变。MED 1被证明是miR-1291的潜在靶基因，miR-1291显著抑制其表达。在体内水平，miR-1291的过表达抑制了异种移植肿瘤的生长，并显著抑制了MED 1蛋白的表达。我们的研究表明miR-1291通过MED 1抑制PCa细胞增殖和成瘤，这可能为PCa的诊断和生物治疗提供新的靶点。
miRNAs are important factors involved in the regulation of tumor development. miR-1291 was found to have regulatory effects in many tumors, but its role in prostate cancer (PCa) still remains unclear. We explored the expression of miR-1291 in PCa to reveal its role in regulating the progression of PCa as well as its underlying mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-1291 in PCa tissues and cell lines compared to normal tissues and cell lines. miR-1291 mimics and inhibitors were applied to overexpress or inhibit the level of miR-1291 in PCa cells. The ability of cell proliferation was measured using MTT assay, and cell cycle distribution was determined by flow cytometry. The potential target of miR-1291 was identified via western blot analysis and luciferase assays. Then a xenograft model was established to explore the function of miR-1291 in PCa in vivo. The results revealed that the expression level of miR-1291 was significantly lower in the PCa tissues than that in the normal adjacent tissues. In PCa-derived cells, there was also a downregulated expression level of miR-1291. Overexpression of miR-1291 obviously inhibited DU-145 cell proliferation and induced cell cycle transition from G0/G1 to S phase. However, inhibition of miR-1291 promoted the growth of LNCaP cells, and promoted the cell cycle transition to S phase and G2/M phase. MED1 was proven to be a potential target gene of miR-1291, and miR-1291 significantly inhibited its expression. At the in vivo level, overexpression of miR-1291 inhibited the growth of xenograft tumors and significantly inhibited the expression of MED1 protein. Our study demonstrated that miR-1291 inhibits cell proliferation and tumorigenesis of PCa via MED1, which might provide a novel target for PCa diagnosis and biological therapy.