Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation

Abstract

<p class="first" id="d2095476e243">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 ( <span style="text-decoration: underline">l</span>owly <span style="text-decoration: underline">e</span>xpressed in <span style="text-decoration: underline">r</span>heumatoid <span style="text-decoration: underline">f</span>ibroblast-like <span style="text-decoration: underline">s</span>ynoviocytes), 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. </p>