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Rab27A promotes cellular apoptosis and ROS production by regulating the miRNA-124-3p/STAT3/RelA signalling pathway in

Yang Luo1, Min-Hao Yu1, Ya-Ru Yan2

  • 1Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.

Journal of Cellular and Molecular Medicine
|August 21, 2020
PubMed

Insights

Rab27A is overexpressed in ulcerative colitis (UC) and promotes inflammation, apoptosis, and reactive oxygen species (ROS) by inhibiting miR-124-3p. Targeting Rab27A may offer a new treatment for UC.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background:

  • Ulcerative colitis (UC) pathogenesis involves excessive apoptosis and reactive oxygen species (ROS).
  • The specific molecular mechanisms driving these processes in UC remain unclear.
  • Rab27A's role in UC has not been previously established.

Purpose of the Study:

  • To investigate the role of Rab27A in the pathogenesis of ulcerative colitis.
  • To elucidate the molecular mechanisms by which Rab27A influences apoptosis and ROS production in colonic cells.
  • To evaluate Rab27A as a potential therapeutic target for UC.

Main Methods:

  • Quantification of Rab27A mRNA and protein in UC patient and mouse models.
  • In vitro studies involving knockdown and overexpression of Rab27A in colonic cells stimulated with LPS.
  • Analysis of apoptosis, ROS production, miR-124-3p expression, and STAT3/RelA pathway activation.
  • In vivo experiments using DSS-induced colitis mouse models to assess the effects of Rab27A and miR-124-3p.

Main Results:

  • Rab27A was significantly overexpressed in intestinal epithelial cells of UC patients and DSS-induced colitis mice.
  • Rab27A silencing inhibited inflammation, apoptosis, and ROS production in a colitis mouse model.
  • Rab27A modulated miR-124-3p to regulate apoptosis and ROS production by targeting the STAT3/RelA pathway in colonic cells.
  • Overexpression of miR-124-3p attenuated Rab27A-induced apoptosis and ROS production.

Conclusions:

  • Rab27A plays a critical role in promoting inflammation, apoptosis, and ROS production in ulcerative colitis.
  • Rab27A functions by modulating the miR-124-3p/STAT3/RelA axis.
  • Rab27A represents a promising novel therapeutic target for the treatment and prevention of ulcerative colitis.
Keywords:
DSS-induced colitis modelRab27ASTAT3/RelA signalling pathwaymiR-124-3pulcerative colitis

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