MALAT1 promotes colonic epithelial cell apoptosis and pyroptosis by sponging miR-22-3p to enhance NLRP3 expression

PeerJ. 2024 Nov 18:12:e18449. doi: 10.7717/peerj.18449. eCollection 2024.

Abstract

Background: Colonic epithelial cell apoptosis and pyroptosis had a close relationship with the pathological progression of ulcerative colitis (UC). LncRNA play a crucial role in the progression of UC. However, the role of the lncRNA MALAT1 in colonic epithelial cell apoptosis and pyroptosis remains unclear.

Methods: UC colitis cell model was established through lipopolysaccharide (LPS) treatment. MiR-22-3p and MALAT1 expression in fetal human colon (FHC) cells were analyzed by qRT-PCR. Proliferation and apoptosis of FHCs were measured using CCK-8 assay and flow cytometry, respectively. Pyroptosis indicators including interleukin (IL)-1β, IL-18, tumor necrosis factor-α (TNF-α), NLR family pyrin domain containing 3 (NLRP3), caspase-1, and N-gasdermin D (N-GSDMD) in FHCs were detected using ELISA, qRT-PCR, western blotting, and immunofluorescence.

Results: In this study, apoptosis was facilitated, IL-1β, IL-18, and TNF-α levels were enhanced, NLRP3, caspase-1, N-GSDMD protein were increased, and MALAT1 expression was markedly increased in LPS-treated FHCs (LTFs). MALAT1 knockdown remarkably facilitated proliferation and suppressed apoptosis, reduced IL-1β, IL-18, and TNF-α levels, and decreased the protein of NLRP3, caspase-1, N-GSDMD. Furthermore, NLRP3 overexpression remarkably reversed the effect of MALAT1-downexpression in LTFs. In addition, miR-22-3p could bind with MALAT1 and NLRP3 3' UTR. Furthermore, miR-22-3p inhibition remarkably reversed the effect of MALAT1 overexpression in LTFs.

Conclusions: These findings suggest that MALAT1 represents a promising therapeutic target for the treatment of UC by modulating the miR-22-3p/NLRP3 pathway, potentially leading to novel strategies for reducing inflammation and cell death in the colon.

Keywords: Fetal human colon cell; Inflammasome; Long non-coding RNAs; Proliferation.

MeSH terms

  • Apoptosis*
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cell Proliferation
  • Colitis, Ulcerative* / genetics
  • Colitis, Ulcerative* / metabolism
  • Colitis, Ulcerative* / pathology
  • Colon* / metabolism
  • Colon* / pathology
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / pharmacology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Pyroptosis*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • MIRN22 microRNA, human
  • RNA, Long Noncoding
  • NLRP3 protein, human
  • MALAT1 long non-coding RNA, human
  • Lipopolysaccharides
  • Interleukin-1beta
  • Interleukin-18
  • Tumor Necrosis Factor-alpha
  • Caspase 1

Associated data

  • figshare/10.6084/m9.figshare.26367505.v2

Grants and funding

This work was funded by grants from the Medical Science and Technology Research Fund Project of Guangdong Province (No. A2019547) and the Science and Technology Project of Zengcheng District, Guangzhou (No. ZCKJ2019-003). The Medical Science and Technology Research Fund project of Guangdong Province (B2024099) supported the APC of this article. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.