lncRNA MEG3 Alleviates Rheumatoid Arthritis by Degrading EZH2 to Promote BTG2 Accumulation

Jinying Hao, Lei Zhou, Zhengyu Zhang, Yaqin Geng, Yu Zhang, Yan Wang, Bo Gao

Article ID: 7219
Vol 37, Issue 3, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233703.164
Received: 8 April 2023; Accepted: 8 April 2023; Available online: 8 April 2023; Issue release: 8 April 2023

Abstract

Background: Overexpression of long non-coding RNA (lncRNA) Maternally Expressed 3 (MEG3) significantly alleviates the inflammatory response caused by rheumatoid arthritis (RA). However, the regulatory effect of lncRNA MEG3 combined with transcription factors remains unknown in RA. Methods: Clinical synovial tissues were collected from The Second People’s Hospital of Changzhou. Histological changes of synovial tissues and cellular morphology were examined by hematoxylin-eosin and immunofluorescent staining. A real-time quantitative polymerase chain reaction as well as a western blot test were used to analyze gene transcript levels. Cell mobility and proliferation of fibroblast-like synoviocytes (FLSs) were assessed according to colony formation, wound healing and transwell assays. Cytokine contents were quantified using enzyme-linked immuno sorbent assay kits. Interactions were analyzed using RNA pull-down and chromatin immunoprecipitation assays. Results: lncRNA MEG3 was significantly downregulated in RA participants’ synovial tissues (p < 0.05) and rats (p < 0.001). Short interference RNA of lncRNA (si-lncRNA) MEG3 significantly reduced cell growth, migration, invasion and inflammatory level of FLSs, while MEG3 overexpression caused in the reverse results. BTG Anti-Proliferation Factor 2 (BTG2) was shown to be significantly inhibited in RA, and the regulatory effects of BTG2 overexpression on cell activity and inflammation were significantly inhibited by si-lncRNA MEG3. Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2) was confirmed to be regulated by lncRNA MEG3, further to control the transcription of BTG2. Si-EZH2 significantly inhibited cell activity and inflammatory level of FLSs, which was similar to the effects of si-lncRNA MEG3. Conclusions: lncRNA MEG3 regulated the expression of BTG2 to participate in RA progression via targeting EZH2, which provided a novel molecular mechanism of RA.


Keywords

rheumatoid arthritis;long non-coding RNA Maternally Expressed 3;Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit;BTG Anti-Proliferation Factor 2;fibroblast-like synoviocytes


References

Supporting Agencies



Copyright (c) 2023 Jinying Hao, Lei Zhou, Zhengyu Zhang, Yaqin Geng, Yu Zhang, Yan Wang, Bo Gao




This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).