LncRNA PICSAR Promotes Cell Proliferation, Migration and Invasion of Fibroblast-Like Synoviocytes by Sponging miRNA-4701-5p in Rheumatoid Arthritis

Abstract

Background: Long non-coding RNAs (lncRNAs) have drawn increasing attention because they play a pivotal role in various types of autoimmune diseases, including rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs), a prominent component of hyperplastic synovial pannus tissue, are the primary effector cells in RA synovial hyperplasia and invasion which can lead to joint destruction. In this study, we investigated whether lncRNAs could act as competing endogenous RNAs to regulate the pathological behaviors of RA-FLSs. Methods: LncRNA microarray was conducted to establish lncRNA expression profiles in FLSs isolated from RA patients and healthy controls (HCs). Differentially expressed lncRNAs were verified by quantitative real-time PCR (qRT-PCR). The functional role of lncRNA PICSAR downregulation was evaluated in RA-FLSs. We conducted molecular biological analysis to predict miRNAs which have a potential binding site for PICSAR and further refined the results by qRT-PCR. Luciferase reporter assay was adopted to validate the interaction of lncRNA PISCAR and miRNA-4701-5p. The functional role of miR-4701-5p upregulation was examined in in RA-FLSs. Findings: We identified a long intergenic non-protein-coding RNA162 (LINC00162), also known as lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA), has significantly higher expression in RA-FLSs and was directly associated with cell proliferation, migration and invasion of RA-FLSs. Mechanistically, lncRNA PISCAR functioned through sponging miR-4701-5p in RA-FLSs. Interpretation: Our results reveal PISCAR may exert an essential role in promoting synovial invasion and joint destruction by sponging miRNA-4701-5p in RA and that targeting lncRNA PISCAR may have therapeutic potential on RA patients. Funding Statement: This work was supported by grants provided from the National Natural Science Foundation of China (81771750; 81671611 to YFP); Program from Guangdong Introducing Innovative and Entrepreneurial Teams (2016ZT06S252 to YFP); NIH R01 AR059103, R61 AR073409 and NIH STAR award (to SGZ). Declaration of Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethics Approval Statement: The research was approved by the ethics committee of the Third Affiliated Hospital of Sun Yat-sen University and all subjects provided the written informed consent in this study according to the Declaration of Helsinki principles.