MicroRNA-590-5p Inhibits Intestinal Inflammation by Targeting YAP.

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 3'-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.

• Authors: Minhao Yu, Yang Luo, Zhijie Cong, Yifei Mu, Yier Qiu, Ming Zhong
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 12 Issue 8 Pg. 993-1004 (Jul 30 2018) ISSN: 1876-4479 [Electronic] England
• PMID: 29912317 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• Adaptor Proteins, Signal Transducing
• Cell Cycle Proteins
• MIRN590 microRNA, human
• MIRN590 microRNA, mouse
• MicroRNAs
• Phosphoproteins
• RNA, Messenger
• Transcription Factors
• YAP-Signaling Proteins
• YAP1 protein, human
• Yap1 protein, mouse
• Verteporfin

Topics

• 3' Untranslated Regions
• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Animals
• Caco-2 Cells
• Cell Cycle Proteins
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Colitis (chemically induced, genetics, metabolism)
• Crohn Disease (genetics, metabolism)
• Epithelial Cells (metabolism)
• Female
• Humans
• Intestinal Mucosa (metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Phosphoproteins (genetics, metabolism)
• RNA, Messenger (metabolism)
• Signal Transduction
• Transcription Factors
• Transfection
• Up-Regulation
• Verteporfin (pharmacology)
• YAP-Signaling Proteins