MicroRNA-590-5p Inhibits Intestinal Inflammation by Targeting YAP. (18th April 2018)

• Record Type: Journal Article
• Authors: Yu, Minhao; Luo, Yang; Cong, Zhijie; Mu, Yifei; Qiu, Yier; Zhong, Ming
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 8(2018:Aug.)
• Page Start: 993
• Page End: 1004
• Publication Date: 2018-04-18
• Subjects: Crohn's disease -- microRNA-590-5p -- YAP1 -- intestinal inflammation -- intestinal epithelial cell; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjy046
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, survival, apoptosis, and stem cell self-renewal. In addition, Hippo signalling is profoundly implicated in intestinal regeneration and cancer. However, its roles in the pathogenesis of Crohn's disease [CD] remain largely unexplored. Methods: Quantitative reverse transcription-polymerase chain reaction [qRT-PCR] was performed to identify the deregulated molecules in Hippo signalling. Expression of the highly upregulated Yes-associated protein 1 [YAP] was subsequently examined by qRT-PCR, western blotting, and immunohistochemistry in the intestinal tissues of CD patients and the colons of 2, 4, 6-trinitrobenzene sulphonic acid [TNBS]-induced colitis mice. The microRNAs [miRNAs] predicted to target YAP were explored by transfection of miR-590-5p mimics or inhibitors and analyzed by luciferase reporter assay. The roles of the miR-590-5p/YAP axis in CD and colorectal cancer were studied in experimental colitis mice and colorectal cancer cell lines. Results: YAP mRNA was significantly upregulated in intestinal epithelial cells in CD patients and TNBS-induced colitis mice. MiR-590-5p suppressed YAP expression by directly targeting the YAP 3ʹ-untranslated region in Caco-2 cells and SW620 cells. Upregulation of miR-590-5p in colon reduced YAP level and its downstream targets in intestinal epithelial cells [IECs]. Treatment of miR-590-5p or YAP inhibitor Verteporfin alleviated experimental colitis. Targeting the miR-590-5p/YAP axis inhibited cell proliferation and invasiveness of colorectal cancer [CRC] cells in vitro. Conclusions: Our results suggest that miR-590-5p inhibits intestinal inflammation in mouse colon and tumourigenesis of colorectal cancer cells by inhibiting YAP. The miR-590-5p/YAP axis may be an important novel mechanism in the pathogenesis of CD and colorectal cancer.