LncRNA OSER1-AS1 regulates the inflammation and apoptosis of rheumatoid arthritis fibroblast like synoviocytes via regulating miR-1298-5p/E2F1 axis

Bioengineered. 2022 Mar;13(3):4951-4963. doi: 10.1080/21655979.2022.2037854.

Abstract

It has been reported that long noncoding RNAs (LncRNAs) take part in the progression and occurrence of rheumatoid arthritis (RA). The current work aimed to dig the effect of lncRNA OSER1-AS1 on RA and the associated mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was made to decide that OSER1-AS1 was significantly lowly expressed in synovial tissue and serum of RA patients, which was consistent in RA-FLSs cell lines. The result of ROC curve indicated that OSER1-AS1 could be a diagnostic biomarker for RA patients. Cell Counting Kit-8 assay (CCK-8), EdU staining and flow cytometry were performed to explore the effect of OSER1-AS1 on RA-FLSs in vitro. Relative levels of interleukin-1 (IL-1), interleukin-6 (IL-6), matrix metalloproteinases-3 (MMP-3) were detected by ELISA and the result displayed that overexpression of OSER1-AS1 inhibited RA-induced inflammatory production of IL-1, IL-6 and MMP3. Bioinformatics analysis, luciferase reporter, RNA immunoprecipitation assays (RIP) and RNA pull-down assay were conducted to confirm the binding between microRNA-1298-5p (miR-1298-5p) and OSER1-AS1 or E2F transcription factor 1 (E2F1). Mechanistically, OSER1-AS1 serves as a competing endogenous (ceRNA) in RA-FLSs through the sponge of miR-1298-5p and increase in the expression of E2F1. Further restoration experiments revealed that miR-1298-5p mimics and E2F1 silencing could partially reverse the inhibiting effect of OSER1-AS1 overexpression on propagation and apoptosis in RA-FLSs. The results illustrated the biological mechanism of OSER1-AS1/miR-1298-59/E2F1 axis in RA progression. The outcomes indicated that OSER1-AS1 might be adopted as a hopeful diagnostic and therapeutic objective for RA.

Keywords: E2F1; OSER1-AS1; miR-1298-5p; rheumatoid arthritis.

MeSH terms

  • Apoptosis / genetics
  • Arthritis, Rheumatoid* / genetics
  • Arthritis, Rheumatoid* / metabolism
  • Cell Proliferation / genetics
  • E2F1 Transcription Factor* / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Synoviocytes* / metabolism

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Interleukin-1
  • Interleukin-6
  • MIRN1298 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

No funding was received for this study.