THU0054 Long non-coding rna gaplinc promotes proliferation and invasion of fibroblast-like synoviocytes as microrna sponging in ra patients

Background Accumulating evidence suggested that long non-coding RNAs (lncRNAs) play diverse functional roles in many autoimmune diseases including rheumatoid arthritis (RA). However, there is a dearth of knowledge in what role these transcripts play in fibroblast-like synoviocytes (FLSs) of RA patients. LncRNA GAPLINC, a novel long non-coding RNA, was first described in gastrointestinal cancer tissues and associated with bad behaviours of tumour cell as well as poor prognosis in patients. Objectives This study was undertaken to explore the expression and roles of LncRNA GAPLINC in RA-FLSs and investigate its possible mechanism. Methods RA-FLSs and trauma-FLSs were cultured from synovial specimens. The expression of RNA was detected by qRT-PCR. GAPLINC suppression was transfected by siRNA. Cell viability analysis was taken by CCK-8 assay and flow cytometry. Cell invasion was using transwell chamber methodology. The bioinformatics analysis was performed using miRanda, PITA, RNAhybrid algorithms, as well as KEGG and Gene Ontology(GO) analysis. Results The relative expression of LncRNA GAPLINC was significantly higher in RA-FLSs than trauma-FLSs (p ). Transfection of GAPLINC-siRNA significantly decreased the expression of LncRNA GAPLINC in RA-FLSs. GAPLINC suppression in RA-FLSs revealed significant alterations in cell proliferation and invasion. In the GAPLINC-siRNA group, a inhibition rate in growth was first observed (15.29%±0.38%) at 24 hour after transfection, then a significant suppression was observed (28.75%±2.34%) at 48 hour, more apparent (36.63%±7.93%) at 72 hour and largely maintained (35.97%±3.67%) at 96 hour after siRNA treatment, compared to the negative control group(NC-siRNA). Moreover, flow cytometry assay showed GAPIINC-siRNA group had an accumulation of cells in the G0/G1 phase and the decreased number of RA-FLSs in the S and G2/M phase. In the invasive assay, the membrane-invading RA-FLSs numbers decreased significantly in the treatment group with GAPLINC knockdown (45.0±3.0) compared to values observed in the NC-siRNA group (149.0±7.0). Above comparisons were all statistically significant (p . The bioinformatics analysis predicted that some of microRNAs and mRNA may be the downstream molecules of LncRNA GAPLINC, we thus simulated a gene co-action network model based on the competitive endogenous RNA (ceRNA) hypothesis. Further verification of this model demonstrated that silencing of GAPLINC increased miR-382–5 p and miR-575 expression. Conclusions The results suggest that elevated LncRNA GAPLINC expression promote the proliferation and invasion of RA-FLSs and it may function as a novel microRNAs sponging agent. Additionally, LncRNA GAPLINC may regulate RA-FLS pathological behaviours in an miR-382–5 p-dependent and miR-575-dependent manner. Based upon these findings, lncRNA GAPLINC may provide a novel valuable therapeutic target for RA patients. Acknowledgements This work was supported by grants from Province Natural Science Fund of Guangdong, China No.2014 A030313080) and National Natural Science Foundation of China (No.81771750). Disclosure of Interest None declared