Long Non-Coding RNA AL928768.3 Promotes Rheumatoid Arthritis Fibroblast-Like Synoviocytes Proliferation, Invasion and Inflammation, While Inhibits Apoptosis Via Activating Lymphotoxin Beta Mediated NF-κB Signaling Pathway

Our previous study using RNA sequencing and reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation identified a long non-coding RNA (lnc), lnc-AL928768.3, correlating with risk and disease activity of rheumatoid arthritis (RA), then the present study was conducted to further investigate the interaction of lnc-AL928768.3 with lymphotoxin beta (LTB) and their impact on proliferation, migration, invasion, and inflammation in RA-fibroblast-like synoviocytes (RA-FLS). Human RA-FLS was obtained and transfected with lnc-AL928768.3 overexpression, negative control overexpression, lnc-AL928768.3 short hairpin RNA (shRNA) and negative control shRNA plasmids. Then cell functions and inflammatory cytokine expressions were detected. Afterward, rescue experiments were conducted via transfecting lnc-AL928768.3 shRNA with or without LTB overexpression plasmids in RA-FLS. Lnc-AL928768.3 enhanced proliferation and invasion, inhibited apoptosis, while had little impact on migration in RA-FLS. In addition, lnc-AL928768.3 positively modulated interleukin-1 beta (IL-1 beta), IL-6 and IL-8 expressions in RA-FLS supernatant; moreover, it also positively regulated LTB mRNA expression, LTB protein expression, p-NF-kappa B protein expression, and p-IKB-alpha protein expression in RA-FLS. Furthermore, following experiment showed that lnc-AL928768.3 positively regulated LTB expression while LTB did not impact on lnc-AL928768.3 expression in RA-FLS. Furthermore, in rescue experiments, LTB overexpression curtailed the effect of lnc-AL928768.3 knock-down on regulating proliferation, invasion, apoptosis and inflammatory cytokine expressions in RA-FLS. Lnc-AL928768.3 promotes proliferation, invasion, and inflammation while inhibits apoptosis of RA-FLS via activating LTB mediated NF-kappa B signaling.