An imbalance in pro- and anti-inflammation is an important mechanism of steroid resistance in UC (ulcerative colitis), and miRNAs may participate in this process. The present study aimed to explore whether miRNAs play a role in the steroid resistance of UC by regulating gene expression of the inflammation signal pathway. SS (steroid-sensitive) patients, SR (steroid-resistant) patients and healthy individuals were recruited. In vivo miRNA profiles of serum samples showed that miR-195 was decreased significantly in the SR group compared with the SS group (P<0.05). This result was confirmed by qPCR (quantitative real-time PCR) and miRNA ISH (in situ hybridization) in serum and colon tissue samples. Online software was used to identify Smad7 mRNA as a potential target of miR-195. The direct interaction of miR-195 and Smad7 mRNA was investigated using a biotinylated miR-195 pull-down assay. Overexpression of a miR-195 precursor lowered cellular levels of Smad7 protein; conversely, antagonism of miR-195 enhanced Smad7 translation without disturbing Smad7 mRNA levels. A luciferase reporter assay revealed a repressive effect of miR-195 via a single Smad7 3′-UTR target site, and point mutation of this site prevented miR-195-induced repression of Smad7 translation. Furthermore, increased levels of miR-195 led to a decrease in c-Jun and p65 expression. In contrast, transfection with anti-miR-195 led to increased levels of c-Jun and p65 protein. The decrease in miR-195 led to an increase in Smad7 expression and corresponding up-regulation of p65 and the AP-1 (activator protein 1) pathway, which might explain the mechanism of steroid resistance in UC patients.
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Research Article|
October 16 2015
miR-195 plays a role in steroid resistance of ulcerative colitis by targeting Smad7
Guodong Chen;
Guodong Chen
1
*Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China
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Shan Cao;
Shan Cao
1
*Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China
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Feng Liu;
Feng Liu
*Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China
†Peking University Hepatology Institute, 11 Xizhimen South Street, Beijing 100044, China
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Yulan Liu
Yulan Liu
2
*Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China
2To whom correspondence should be addressed (email liuyulan@pkuph.edu.cn).
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Publisher: Portland Press Ltd
Received:
January 22 2015
Revision Received:
August 12 2015
Accepted:
August 24 2015
Accepted Manuscript online:
August 24 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 471 (3): 357–367.
Article history
Received:
January 22 2015
Revision Received:
August 12 2015
Accepted:
August 24 2015
Accepted Manuscript online:
August 24 2015
Citation
Guodong Chen, Shan Cao, Feng Liu, Yulan Liu; miR-195 plays a role in steroid resistance of ulcerative colitis by targeting Smad7. Biochem J 1 November 2015; 471 (3): 357–367. doi: https://doi.org/10.1042/BJ20150095
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