title: MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1.
abstract: OBJECTIVE
  While it's widely accepted that the etiology of ulcerative colitis (UC) involves both genetic and environmental factors, the pathogenesis of ulcerative colitis is still poorly understood. Intestinal epithelial apoptosis is one of the most common histopathological changes of UC and the expression of a number of apoptosis genes may contribute to the progression of UC. MicroRNAs have recently emerged as powerful regulators of diverse cellular processes and have been shown to be involved in many immune-mediated disorders such as psoriasis, rheumatoid arthritis, lupus, and asthma. A unique microRNA expression profile has been identified in UC, suggesting that, microRNAs play an important role in the pathogenesis of UC. We investigated the role of miR-29a in intestinal epithelial apoptosis in UC.
  
  
  METHODS
  The expression of miR-29a and Mcl-1, an anti-apoptotic BCL-2 family member, was evaluated in both UC patients and UC mice model induced by dextran sodium sulfate (DSS). The apoptosis rate of intestinal epithelial cells was also evaluated.
  
  
  RESULTS
  In UC patients and DSS-induced UC in mice, the expression of miR-29a and Mcl-1, were up-regulated and down-regulated, respectively. We identified a miR-29a binding site (7 nucleotides) on the 3'UTR of mcl-1 and mutation in this binding site on the 3'UTR of mcl-1 led to mis-match between miR-29a and mcl-1. Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1.
  
  
  CONCLUSIONS
  miR-29a is involved in the pathogenesis of UC by regulating intestinal epithelial apoptosis via Mcl-1.
authors: Guangdong General Hospital, Guangdong Academy of Medical Sciences China.
authors: Bo
authors: B
authors: Lv
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Zhihui
authors: Z
authors: Liu
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Shuping
authors: S
authors: Wang
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Fengbin
authors: F
authors: Liu
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Xiaojun
authors: X
authors: Yang
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Jiangtao
authors: J
authors: Hou
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Zhengkun
authors: Z
authors: Hou
authors: First School of Clinic Medicine & First Affiliated Hospital of Guangzhou University of Chinese Medicine China.
authors: Bin
authors: B
authors: Chen
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C579095:MCL1 protein, human; C547014:MIRN29 microRNA, mouse; C532045:MIRN29a microRNA, human; C579094:Mcl1 protein, mouse; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein
keywords: Mcl-1; MiR-29a; apoptosis; ulcerative colitis