Background/Purpose:  Emerging evidence indicates that long noncoding RNAs (lncRNAs) play critical regulatory roles in various human diseases, especially in cancers and inflammatory disorders. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains largely unknown.

Methods:  Fibroblast-like synoviocytes (FLSs) were separated and cultured from synovial tissues of healthy control (HC) and RA patients. Differentially expressed lncRNAs between HC and RA FLSs were identified by microarray. Expression level and subcellular localization of RNA was validated by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Transcriptional initiation and termination sites of NR_122076 were identified by rapid amplification of cDNA ends (RACE) analysis. Lentivirus mediated overexpression of NR_122076 were adopted to investigate the function of NR_122076. Proliferation rate was assessed by EdU assay. Migration and invasion of FLSs in vitro were measured by the Boyden chamber assay. Cytoskeleton was visualized by immunofluorescence.

Results:  We used microarray to establish lncRNA expression profiles in FLSs from HC and RA patients. We found that 94 lncRNAs were upregulated and 195 lncRNAs downregulated by more than 2-fold in RA FLSs compared with HC FLSs. Further qRT-PCR confirmed that, among them, only NR_122076 expression was significantly decreased in the synovial tissues and FLSs from RA patients. Stimulation with PDGF-BB decreased the expression of NR_122076, whereas treatments of methotrexate or dexamethasone increased NR_122076 expression. RNA fluorescent in situ hybridization (FISH) and qRT-PCR of nuclear and cytoplasmic fractions suggested that NR_122076 was mainly located in the cytoplasm. Overexpression of NR_122076 significantly inhibited cell proliferation, migration and invasion in RA FLSs. Furthermore, overexpression of NR_122076 impaired PDGF-BB induced formation of lamillipodia and filopodia.

Conclusion: Decreased expression of NR_122076 contributes to excessive proliferation and aberrant aggressive behaviors of RA FLSs. Our findings suggest NR_122076 might be a possible new therapeutic target against RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lower-expression-of-a-novel-cytoplasmic-long-noncoding-rna-nr_122076-contributes-to-proliferation-migration-and-invasion-of-fibroblast-like-synoviocytes-from-patients-with-rheumatoid-arthritis/