m6A-mediated lncRNA MAPKAPK5-AS1 induces apoptosis and suppresses inflammation via regulating miR-146a-3p/SIRT1/NF-κB axis in rheumatoid arthritis

被引:10
作者
Wen, Jianting [1 ,2 ,3 ]
Liu, Jian [1 ,2 ,4 ,5 ]
Wan, Lei [1 ,2 ,4 ]
Jiang, Hui [1 ,4 ]
Xin, Ling [1 ,4 ]
Sun, Yue [1 ,4 ]
Fang, Yanyan [1 ,4 ]
Wang, Xin [1 ,4 ]
Wang, Jie [1 ,4 ]
机构
[1] Anhui Univ Chinese Med, Dept Rheumatol & Immunol, Affiliated Hosp 1, Hefei, Anhui Province, Peoples R China
[2] Anhui Acad Chinese Med, Inst Rheumatol, Hefei, Anhui Province, Peoples R China
[3] Anhui Univ Chinese Med, Key Lab Xinan Med, Minist Educ, Hefei, Anhui, Peoples R China
[4] Anhui Prov Key Lab Modern Chinese Med, Dept Internal Med Applicat Fdn Res & Dev, Hefei, Anhui, Peoples R China
[5] Anhui Univ Chinese Med, Dept Rheumatol & Immunol, Affiliated Hosp 1, 117 Meishan Rd, Hefei 230031, Anhui Province, Peoples R China
关键词
Rheumatoid arthritis; MAPKAPK5-AS1; ceRNA; m(6)A; apoptosis; inflammatory responses; FIBROBLAST-LIKE SYNOVIOCYTES; MESSENGER-RNA; M(6)A; PROLIFERATION; TRANSLATION; METHYLATION; PROGRESSION; INHIBITOR; MICRORNAS; PROMOTES;
D O I
10.1080/15384101.2024.2302281
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To investigate the role of m(6)A-mediated lncRNA MAPKAPK5-AS1 (MK5-AS1) in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) and its underlying molecular mechanism. RT-qPCR, western blot, flow cytometry (FCM), and enzyme-linked immunosorbent assay (ELISA) were utilized for evaluating inflammation and apoptosis. Next, RIP, RNA pull-down, dual-luciferase reporter gene assay, and a series of rescue experiments were performed to explore the regulatory mechanisms of MK5-AS1 and its sponge-like action in RA-FLSs. The regulatory relationships between MK5-AS1 and WTAP were explored using the MeRIP-qPCR assay and RT-qPCR. Finally, the critical RNAs in the ceRNA axis were verified in the clinical cohort. MK5-AS1 was poorly expressed and miR-146a-3p was overexpressed in co-cultured RA-FLSs. MK5-AS1 overexpression could inhibit inflammatory responses and promote cell apoptosis in the co-cultured RA-FLSs. MK5-AS1 bound to miR-146a-3p to target SIRT1, thereby affecting inflammatory responses and cell apoptosis in the co-cultured RA-FLSs. SIRT1 knockdown or miR-146a-3p overexpression reversed the impacts of MK5-AS1 overexpression on co-cultured RA-FLSs inflammation and apoptosis. Moreover, WTAP was downregulated, and induced the inhibition of MK5-AS1 by promoting its RNA transcript stability. Clinically, MK5-AS1 was downregulated in RA-PBMCS and correlated with the clinical characteristics of RA. Our study elucidated that m6A-mediated MK5-AS1 sequestered miR-146a-3p to suppress SIRT1 expression in co-cultured RA-FLSs, thus providing a new insight into the treatment of rheumatoid arthritis.
引用
收藏
页码:2602 / 2621
页数:20
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