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miR-335-5p对CCRK的靶向调控对人肾癌细胞增殖及致瘤性的影响

Effects of the Targeted Regulation of CCRK by miR-335-5p on the Proliferation and Tumorigenicity of Human Renal Carcinoma Cells.

作者信息

Zuo Xiaojia, Lu Chaojun, Zheng Yanjun, Lai Donglin, Liu Dingsheng, Wan Guoqing, Lu Changlian, Gu Xuefeng

机构信息

Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Science, Shanghai, China.

Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China.

出版信息

J Oncol. 2022 Oct 14;2022:2960050. doi: 10.1155/2022/2960050. eCollection 2022.

Abstract

Cell cycle-related kinase (CCRK) is most closely related to cyclin-dependent protein kinase, which may activate cyclin-dependent kinase 2 and is associated with the growth of human cancer cells. However, the expression and function of CCRK in the pathogenesis of clear cell renal cell cancer (ccRCC) are unclear. Herein, this research aimed to explore the potential mechanism of the targeted regulation of CCRK by miR-335-5p on the proliferation and tumorigenicity of human ccRCC cells. The results showed that CCRK was significantly overexpressed in ccRCC tissues and cells, and knockdown of the CCRK expression by shRNA inhibited cell proliferation and and enhanced cell apoptosis , which indicated that CCRK could be a potential target for antitumour drugs in the treatment of ccRCC. Moreover, miR-335-5p was found to bind directly to the 3' untranslated region of CCRK, was expressed at markedly low levels in ccRCC cells, and was closely associated with the tumour stage. The overexpression of CCRK partially reversed the inhibitory effects of miR-335-5p on the cell growth of ccRCC, which implied that miR-335-5p could serve as a promising tumour inhibitor for ccRCC. In summary, CCRK could serve as an alternative antitumour drug target, and miR-335-5p could be a promising therapeutic tumour inhibitor for ccRCC treatment.

摘要

细胞周期相关激酶(CCRK)与细胞周期蛋白依赖性蛋白激酶关系最为密切,它可能激活细胞周期蛋白依赖性激酶2,并与人类癌细胞的生长相关。然而,CCRK在透明细胞肾细胞癌(ccRCC)发病机制中的表达和功能尚不清楚。在此,本研究旨在探讨miR-335-5p靶向调控CCRK对人ccRCC细胞增殖和致瘤性的潜在机制。结果显示,CCRK在ccRCC组织和细胞中显著过表达,通过shRNA敲低CCRK表达可抑制细胞增殖并增强细胞凋亡,这表明CCRK可能是ccRCC治疗中抗肿瘤药物的潜在靶点。此外,发现miR-335-5p直接与CCRK的3'非翻译区结合,在ccRCC细胞中表达明显较低,且与肿瘤分期密切相关。CCRK的过表达部分逆转了miR-335-5p对ccRCC细胞生长的抑制作用,这意味着miR-335-5p可能是一种有前景的ccRCC肿瘤抑制剂。总之,CCRK可作为一种替代的抗肿瘤药物靶点,而miR-335-5p可能是ccRCC治疗中有前景的治疗性肿瘤抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01be/9586783/c756572af02e/JO2022-2960050.001.jpg

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