Rheumatoid Arthritis

LOC100912373[LncRNA]

miR-17-5p[miRNA]

AKT[mRNA]

fibroblast-like synoviocytes

Homo sapiens (human)

Am J Transl Res. 2020 Dec 15;12(12):7709-7723. eCollection 2020.

LncRNA LOC100912373 modulates PDK1 expression by sponging miR-17-5p to promote the proliferation of fibroblast-like synoviocytes in rheumatoid arthritis.

qPCR;RT-qPCR;RNA immunoprecipitation;Western blot;Flow Cytometry assay;RNA immunoprecipitation;

Rheumatoid arthritis (RA) is a common autoimmune disease and characterized by chronic inflammation, abnormal synovial cell proliferation, and joint swelling and tenderness, and it causes patients substantial pain. To date, the pathogenesis of RA remains unclear, and specific treatment is still lacking in the clinic. Evidence from previous research indicated that the long noncoding RNA (lncRNA) LOC100912373 is a key lncRNA and involved in RA. However, our understanding of the specific mechanism of lncRNA LOC100912373 in RA development and progression is still in its infancy. In this study, fibroblast-like synoviocytes (FLSs) were cultured by enzyme-dispersed and substrate-attached explant methods. The MTT method, flow cytometry and transmission electron microscopy were used to determine the effect of lncRNA LOC100912373 on FLSs. The expression of key genes such as lncRNA LOC100912373, miR-17-5p, PDK1 and AKT in FLSs was detected by RT-qPCR, immunofluorescence and Western blot. The localization of lncRNA LOC100912373 was determined by fluorescence in situ hybridization. The specific targeting relationship between lncRNA LOC100912373 and miR-17-5p/PDK1 was verified by RNA immunoprecipitation and luciferase reporter gene analysis. The results showed that lncRNA LOC100912373 localized in the cytoplasm and was highly expressed in the synovial tissues and FLSs of AA rats. LncRNA LOC100912373 overexpression promoted the proliferation of FLSs. In addition, lncRNA LOC100912373 could bind to miR-17-5p, and the expression of lncRNA LOC100912373 was negatively correlated with miR-17-5p and positively correlated with PDK1/AKT. In conclusion, lncRNA LOC100912373 may upregulate the expression of PDK1 by sponging miR-17-5p, accelerating the phosphorylation of AKT and inducing the proliferation of FLSs, thus promoting the occurrence and development of RA.