miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway

Journal of Orthopaedic Surgery and Research

Zhiyun Li¹  Botao Zhu¹  Peilong Dong¹  Jian Wang¹  Xiaobo Tang¹ 

[1] Department of Orthopedics, Affiliated Jianhu Hospital of Nantong University, No. 666 Nanhuan Road, Jianhu, 224700, Yancheng, Jiangsu, People’s Republic of China;

关键词: miR-653-5p;    FGF2;    Rheumatoid arthritis;    Fibroblast-like synoviocytes;   

DOI  :  10.1186/s13018-021-02887-4

来源: Springer

【 摘 要 】

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells.MethodsThe mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2.ResultsRT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3′-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition.ConclusionIn sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway.

【 授权许可】

CC BY