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微小RNA-106b-5p通过直接靶向骨肉瘤中的细胞周期蛋白依赖性激酶抑制剂1A来促进细胞增殖和细胞周期进程。

miR-106b-5p promotes cell proliferation and cell cycle progression by directly targeting CDKN1A in osteosarcoma.

作者信息

He Chuan, Chen Hongwei, Liu Yan, Li Xiaolin, Zhang Chaoju, Qin Qunyan, Pang Qixiong

机构信息

Department of Orthopedics, Jingzhou Traditional Chinese Medicine Hospital, Jingzhou, Hubei 434000, P.R. China.

Bone Injury Teaching and Research Office, The Third Clinical Medical School of Yangtze University, Jingzhou, Hubei 434000, P.R. China.

出版信息

Exp Ther Med. 2020 May;19(5):3203-3210. doi: 10.3892/etm.2020.8574. Epub 2020 Mar 6.

Abstract

MicroRNA (miR)-106b-5p has been reported to act as both an oncogene and tumor suppressor in several tumors. The aim of the present study was to investigate the biological function of miR-106b-5p in osteosarcoma (OS). miR-106b-5p expression was observed to be significantly increased in OS tissues and cell lines. MTT assay and flow cytometry analysis determined that miR-106b-5p inhibitor transfection suppressed OS cell proliferation and induced cell cycle G0/G1 phase arrest. Furthermore, bioinformatics analysis and a luciferase reporter assay demonstrated that cyclin-dependent kinase inhibitor 1A (CDKN1A) was a potential target of miR-106b-5p. p21 protein expression was found to be significantly increased by miR-106b-5p downregulation in OS cells. Further analysis demonstrated that CDKN1A was downregulated in OS tissues and was negatively correlated with miR-106b-5p expression. Furthermore, upregulation of CDKN1A expression mimicked, whilst CDKN1A knockdown reversed the suppressive effects of miR-106b-5p inhibitor on OS cell proliferation and cell cycle progression. In summary, the present data suggested that miR-106b-5p promotes cell proliferation and cell cycle progression by directly targeting CDKN1A in OS.

摘要

据报道,微小RNA(miR)-106b-5p在多种肿瘤中既作为癌基因又作为肿瘤抑制因子发挥作用。本研究的目的是探讨miR-106b-5p在骨肉瘤(OS)中的生物学功能。观察到miR-106b-5p在OS组织和细胞系中的表达显著增加。MTT法和流式细胞术分析确定,转染miR-106b-5p抑制剂可抑制OS细胞增殖并诱导细胞周期G0/G1期阻滞。此外,生物信息学分析和荧光素酶报告基因检测表明,细胞周期蛋白依赖性激酶抑制剂1A(CDKN1A)是miR-106b-5p的潜在靶点。发现miR-106b-5p下调可使OS细胞中p21蛋白表达显著增加。进一步分析表明,CDKN1A在OS组织中表达下调,且与miR-106b-5p表达呈负相关。此外,CDKN1A表达上调模拟了miR-106b-5p抑制剂对OS细胞增殖和细胞周期进程的抑制作用,而敲低CDKN1A则逆转了这种抑制作用。总之,目前的数据表明,miR-106b-5p通过直接靶向OS中的CDKN1A促进细胞增殖和细胞周期进程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d92/7132225/934e835ce0a1/etm-19-05-3203-g00.jpg

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