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微小RNA-195通过调控高迁移率族蛋白A1抑制肾细胞癌的增殖和转移。

MicroRNA-195 inhibits proliferation and metastasis in renal cell carcinoma via regulating HMGA1.

作者信息

Dong Huiyu, Sun Shengjie, Yan Tao, Liang Chao, Zhu Jundong, Miao Chenkui, Qin Chao, Shao Pengfei, Wang Zengjun, Li Jie, Li Pu

机构信息

State Key Laboratory of Reproductive Medicine and Department of Urology, The First Affiliated Hospital of Nanjing Medical University Nanjing, Jiangsu, China.

Department of Urology, The First People's Hospital of Changzhou Changzhou, Jiangsu, China.

出版信息

Am J Transl Res. 2020 Jun 15;12(6):2781-2792. eCollection 2020.

Abstract

Growing evidence indicates that aberrant expression of microRNAs (miRNAs) contributes to tumorigenesis in various human malignancies. In this study we revealed that miR-195 acted as a tumor suppressor in renal cell carcinoma (RCC) through inhibition of HMGA1 expression. qRT-PCR was used to detect the miR-195 expression in RCC tissues and cell lines. RCC cell line Caki-1 and Caki-2 cells were used in this study. The luciferase report assay and rescue assay were performed to identify HMGA1 as the target gene of miR-195. Additionally, Kaplan-Meier method and log-rank test was used to explore the relationship between HMGA1 expression and RCC prognosis. We observed that miR-195 expression was significantly downregulated both in RCC tissues and in RCC cell lines. We observed that miR-195 overexpression inhibits the abilities of RCC cell proliferation, cell cycle progression and metastasis in vitro by targeting HMGA1 via epithelial to mesenchymal transition (EMT) pathway. In clinical specimens, HMGA1 was overexpressed in high-grade RCC when compared with its levels in normal tissues and low-grade RCC cancer, its expression levels were inversely correlated with overall survival. Our findings highlight an important role of miR-195 and HMGA1 in the molecular etiology of RCC, indicating that they can serve as potential biomarkers and therapy targets of RCC.

摘要

越来越多的证据表明,微小RNA(miRNA)的异常表达促成了各种人类恶性肿瘤的发生。在本研究中,我们揭示了miR-195通过抑制HMGA1的表达在肾细胞癌(RCC)中发挥肿瘤抑制作用。采用qRT-PCR检测RCC组织和细胞系中miR-195的表达。本研究使用了RCC细胞系Caki-1和Caki-2细胞。进行荧光素酶报告基因检测和挽救实验以确定HMGA1是miR-195的靶基因。此外,采用Kaplan-Meier法和对数秩检验来探讨HMGA1表达与RCC预后之间的关系。我们观察到,miR-195的表达在RCC组织和RCC细胞系中均显著下调。我们观察到,miR-195过表达通过上皮-间质转化(EMT)途径靶向HMGA1,在体外抑制RCC细胞增殖、细胞周期进程和转移能力。在临床标本中,与正常组织和低级别RCC相比,HMGA1在高级别RCC中过表达,其表达水平与总生存期呈负相关。我们的研究结果突出了miR-195和HMGA1在RCC分子病因学中的重要作用,表明它们可作为RCC潜在的生物标志物和治疗靶点。

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