Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation

• Published in: The Journal of clinical investigation Vol. 128; no. 10; pp. 4510 - 4524
• Main Authors: Zou, Yaoyao, Xu, Siqi, Xiao, Youjun, Qiu, Qian, Shi, Maohua, Wang, Jingnan, Liang, Liuqin, Zhan, Zhongping, Yang, Xiuyan, Olsen, Nancy, Zheng, Song Guo, Xu, Hanshi
• Format: Journal Article
• Language: English
• Published: Ann Arbor American Society for Clinical Investigation 01.10.2018
• Subjects: Aggression; Biomedical research; Cancer; Cdc42 protein; Cell adhesion & migration; Disease; Epigenetics; Fibroblasts; Genomes; Guanosine triphosphatases; Metabolism; Migration; Motility; mRNA; Mutation; Proteins; Rac1 protein; Rheumatoid arthritis; RhoA protein; Roles; Synoviocytes; Translation
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI97965.

Fibroblast-like synoviocytes (FLSs) are critical to synovial aggression and joint destruction in rheumatoid arthritis (RA). The role of long noncoding RNAs (lncRNAs) in RA is largely unknown. Here, we identified a lncRNA, LERFS (jowly expressed in rheumatoid fibroblast-like synoviocytes), that negatively regulates the migration, invasion, and proliferation of FLSs through interaction with heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Under healthy conditions, by binding to the mRNA of RhoA, Rac1, and CDC42 - the small GTPase proteins that control the motility and proliferation of FLSs - the LERFS-hnRNP Q complex decreased the stability or translation of target mRNAs and downregulated their protein levels. But in RA FLSs, decreased LERFS levels induced a reduction of the LERFS-hnRNP Q complex, which reduced the binding of hnRNP Q to target mRNA and therefore increased the stability or translation of target mRNA. These findings suggest that a decrease in synovial LERFS may contribute to synovial aggression and joint destruction in RA and that targeting the lncRNA LERFS may have therapeutic potential in patients with RA.