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Background <p>Rheumatoid arthritis (RA) is a widely prevalent rheumatic condition causing joint inflammation and damage. RNA methylation plays an important role in RA. Herein, we intended to investigate the function of methyltransferase-like 3 (METTL3) and its N6-methyladenosine (m6A) methylation regulation for ras-related C3 botulinum toxin substrate 2 (RAC2) in RA.</p> Methods <p>MH7A cells were treated with TNF‐α to establish RA cell model. The expression analysis was performed by RT-qPCR and western blot. Cellular behaviors were examined by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Oxidative stress was assessed by detecting the associated indicators. Inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). Interaction between METTL3 and RAC2 was analyzed via RNA immunoprecipitation (RIP) assay and MeRIP assay.</p> Results <p>RAC2 was highly expressed in RA tissues and TNF‐α-stimulated MH7A cells. Knockdown of RAC2 enhanced apoptosis and reduced proliferation, migration, invasion after TNF‐α treatment. RAC2 downregulation suppressed oxidative stress and inflammatory response in TNF‐α-treated MH7A cells. METTL3 promoted RAC2 expression through m6A methylated modification, and METTL3/RAC2 could activate AKT pathway. RAC2 overexpression reversed the effects of METTL3 knockdown on cell proliferation, motility, oxidative stress and inflammation.</p> Conclusion <p>The above results demonstrated that METTL3 facilitated the progression of RA via downregulating RAC2 in an m6A dependent mechanism in TNF‐α-treated MH7A cells.</p>

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METTL3-mediated methylation of RAC2 contributes to cell motility, oxidative stress and inflammation in TNF‐α-stimulated rheumatoid arthritis fibroblast-like synovial cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月20日

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  • Hua Ren,
  • Guohua Wei,
  • Ziwei Kong,
  • Mengyang Zhang,
  • Yuejin Li,
  • Sanjiao Liu,
  • Yifan Guo

摘要

Background

Rheumatoid arthritis (RA) is a widely prevalent rheumatic condition causing joint inflammation and damage. RNA methylation plays an important role in RA. Herein, we intended to investigate the function of methyltransferase-like 3 (METTL3) and its N6-methyladenosine (m6A) methylation regulation for ras-related C3 botulinum toxin substrate 2 (RAC2) in RA.

Methods

MH7A cells were treated with TNF‐α to establish RA cell model. The expression analysis was performed by RT-qPCR and western blot. Cellular behaviors were examined by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Oxidative stress was assessed by detecting the associated indicators. Inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). Interaction between METTL3 and RAC2 was analyzed via RNA immunoprecipitation (RIP) assay and MeRIP assay.

Results

RAC2 was highly expressed in RA tissues and TNF‐α-stimulated MH7A cells. Knockdown of RAC2 enhanced apoptosis and reduced proliferation, migration, invasion after TNF‐α treatment. RAC2 downregulation suppressed oxidative stress and inflammatory response in TNF‐α-treated MH7A cells. METTL3 promoted RAC2 expression through m6A methylated modification, and METTL3/RAC2 could activate AKT pathway. RAC2 overexpression reversed the effects of METTL3 knockdown on cell proliferation, motility, oxidative stress and inflammation.

Conclusion

The above results demonstrated that METTL3 facilitated the progression of RA via downregulating RAC2 in an m6A dependent mechanism in TNF‐α-treated MH7A cells.