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微小RNA-138通过直接靶向SOX9抑制肾细胞癌的细胞增殖和侵袭。

MicroRNA-138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9.

作者信息

Hu Bo, Wang Jianbo, Jin Xunbo

机构信息

Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.

Oncology Center, Qilu Hospital of Shandong University, Jinan, Shandong 250000, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):7583-7588. doi: 10.3892/ol.2017.7160. Epub 2017 Oct 10.

Abstract

An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.

摘要

越来越多的研究报告称,微小RNA(miRNA/miR)的表达水平在包括肾细胞癌(RCC)在内的多种人类癌症类型中失调。miRNA通过充当癌基因或肿瘤抑制因子在肿瘤发生和肿瘤进展中发挥重要作用。最近,miR-138在多种人类癌症类型中的表达和功能已得到研究;然而,其在RCC中的作用仍知之甚少。在本研究中,结果显示miR-138在RCC细胞系和组织中显著下调,且miR-138的低表达水平与组织学分级、肿瘤分期和淋巴结转移相关。在功能研究中,miR-138表达的恢复抑制了ACHN和A498细胞的增殖和侵袭。此外,SOX9被证实为RCC中miR-138的直接靶基因。SOX9的敲低抑制了RCC的细胞增殖和侵袭,其效果与miR-138诱导的效果相似,这使得SOX9成为该疾病中miR-138的功能靶点。这些发现表明,miR-138可能是RCC治疗策略的一个新靶点。

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