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METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis

Weiyun Wu1,2, Xiaowen Li1,2, Zhuliang Zhou2

  • 1Laboratory of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, China.

Cell Biology and Toxicology
|November 11, 2024
PubMed

Insights

Methyltransferase-like 14 (METTL14) protects against ulcerative colitis (UC) by regulating the DHRS4-AS1/miR-206/A3AR axis. METTL14 targeting offers a potential therapeutic strategy for UC inflammatory injury.

Area of Science:

  • Molecular biology
  • Immunology
  • Gastroenterology

Background:

  • Ulcerative colitis (UC) pathogenesis remains unclear, but N6-methyladenosine (m6A) RNA modification is implicated.
  • Methyltransferase-like 14 (METTL14) is crucial for m6A modification and its role in UC requires investigation.

Purpose of the Study:

  • To investigate the regulatory role and mechanism of METTL14 in long non-coding RNA (lncRNA) during UC progression.
  • To explore METTL14's potential as a therapeutic target for UC.

Main Methods:

  • Utilized cell viability assays, apoptosis markers (cleaved PARP, cleaved Caspase-3, Bcl-2), NF-κB pathway analysis, and inflammatory cytokine assessment in Caco-2 cells.
  • Employed a dextran sulfate sodium (DSS)-induced murine colitis model to evaluate METTL14's in vivo effects.
  • Investigated the interaction between METTL14, DHRS4-AS1, miR-206, and adenosine A3 receptor (A3AR) using molecular techniques.

Main Results:

  • METTL14 knockdown reduced cell viability, induced apoptosis, and increased NF-κB activation and inflammatory cytokine production.
  • METTL14 suppression aggravated colonic damage and inflammation in the DSS-induced colitis model.
  • METTL14 regulated DHRS4-AS1 expression via m6A modification, and DHRS4-AS1 targeted the miR-206/A3AR axis to mitigate inflammation.

Conclusions:

  • METTL14 plays a protective role in UC by modulating the DHRS4-AS1/miR-206/A3AR pathway.
  • METTL14 represents a promising therapeutic target for ulcerative colitis.
Keywords:
A3ARLncRNA DHRS4-AS1M6A modificationMETTL14MiR-206Ulcerative colitis

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