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miR-1 通过与 c-Met 结合抑制 Akt/mTOR 信号通路从而抑制前列腺癌细胞 PC3 的增殖。

MiR-1 inhibits prostate cancer PC3 cells proliferation through the Akt/mTOR signaling pathway by binding to c-Met.

机构信息

The Second Department of Clinical Oncology, Shengjing Hospital, China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, 110022, China.

School of Computer Science and Engineering, Northeastern University, No. 3-11, Wenhua Road, Heping District, Shenyang, 110004, China.

出版信息

Biomed Pharmacother. 2019 Jan;109:1406-1410. doi: 10.1016/j.biopha.2018.10.098. Epub 2018 Nov 12.

DOI:10.1016/j.biopha.2018.10.098
PMID:30551391
Abstract

Prostate cancer (PC) is known as the most common cancer and is ranked second in cancer-related deaths in males. Accumulating evidence implicates microRNAs (miRNAs) may play key roles in tumorigenesis. We investigated the effects of microRNA-1 (miR-1) on the viability and proliferation of prostate cancer cells and the underlying mechanism. We first detected the miR-1 expression level in the PC cells by quantitative real-time PCR (qRT-PCR). The relation between the level of miR-1 and c-Met was investigated via luciferase reporter assay. Cell viability and proliferation were analyzed via MTT assay and flow cytometry in PC cells. Western blot was used for examining the related signaling pathway. MiR-1 expression was decreased and c-Met expression was increased in PC cells. Subsequently, we found that overexpression of miR-1 could inhibit viability and proliferation of PC cells functionally. Furthermore, the dual luciferase reporter assay results indicated that the c-Met is the target gene of miR-1. Western blot results indicated that this inhibition on the viability and proliferation of PC cells was via regulation of c-Met/AKT/mTOR signaling pathway. In conclusion, this study provides novel insight into the role of miR-1 in PC, and the results demonstrated that miR-1 could inhibit viability and proliferation of PC cells by targeting the c-Met/Akt/mTOR signaling pathway. MiR-1 might be a potential candidate for application in the treatment of PC.

摘要

前列腺癌(PC)是最常见的癌症之一,在男性癌症相关死亡中排名第二。越来越多的证据表明,microRNAs(miRNAs)可能在肿瘤发生中发挥关键作用。我们研究了 microRNA-1(miR-1)对前列腺癌细胞活力和增殖的影响及其潜在机制。我们首先通过定量实时 PCR(qRT-PCR)检测了 PC 细胞中的 miR-1 表达水平。通过荧光素酶报告基因检测研究了 miR-1 水平与 c-Met 之间的关系。通过 MTT 分析和流式细胞术分析了 PC 细胞中的细胞活力和增殖。通过 Western blot 检测了相关信号通路。在 PC 细胞中,miR-1 的表达降低,c-Met 的表达增加。随后,我们发现过表达 miR-1 可以在功能上抑制 PC 细胞的活力和增殖。此外,双荧光素酶报告基因检测结果表明 c-Met 是 miR-1 的靶基因。Western blot 结果表明,这种对 PC 细胞活力和增殖的抑制是通过调节 c-Met/Akt/mTOR 信号通路实现的。总之,本研究为 miR-1 在 PC 中的作用提供了新的见解,结果表明 miR-1 可以通过靶向 c-Met/Akt/mTOR 信号通路抑制 PC 细胞的活力和增殖。miR-1 可能是治疗 PC 的潜在候选药物。

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