Open AccessRab27A promotes cellular apoptosis and ROS production by regulating the miRNA‐124‐3p/STAT3/RelA signalling pathway in ulcerative colitis
Author(s) -
Luo Yang,
Yu MinHao,
Yan YaRu,
Zhou Yong,
Qin ShaoLan,
Huang YiZhou,
Qin Jun,
Zhong Ming
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15726
Subject(s) - apoptosis , gene knockdown , gene silencing , reactive oxygen species , ectopic expression , cancer research , ulcerative colitis , stat3 , chemistry , signal transduction , colitis , microbiology and biotechnology , inflammation , biology , immunology , medicine , gene , pathology , biochemistry , disease
Ulcerative colitis (UC) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of UC pathogenesis is associated with excessive cellular apoptosis and reactive oxygen species (ROS) production. However, their function and molecular mechanisms related to UC remain unknown. In this study, Rab27A mRNA and protein were proven to be overexpressed in intestinal epithelial cells of UC patients and DSS‐induced colitis mice, compared with control ( P < 0.05). And Rab27A silencing inhibits inflammatory process in DSS‐induced colitis mice ( P < 0.05). Then, it was shown that knockdown of Rab27A suppressed apoptosis and ROS production through modulation of miR‐124‐3p, whereas overexpression of Rab27A promoted apoptosis and ROS production in LPS‑induced colonic cells. In addition, enhanced expression of miR‐124‐3p attenuated apoptosis and ROS production by targeting regulation of STAT3 in LPS‑induced colonic cells. Mechanistically, we found Rab27A reduced the expression and activity of miR‐124‐3p to activate STAT3/RelA signalling pathway and promote apoptosis and ROS production in LPS‑induced colonic cells, whereas overexpression of miR‐124‐3p abrogated these effects of Rab27A. More importantly, animal experiments illustrated that ectopic expression of Rab27A promoted the inflammatory process, whereas overexpression of miR‐124‐3p might interfere with the inflammatory effect in DSS‐induced colitis mice. In summary, Rab27A might modulate the miR‐124‐3p/STAT3/RelA axis to promote apoptosis and ROS production in inflammatory colonic cells, suggesting that Rab27A as a novel therapeutic target for the prevention and treatment of UC patients.