Long noncoding RNA KIF9-AS1 promotes cell apoptosis by targeting the microRNA-148a-3p/suppressor of cytokine signaling axis in inflammatory bowel disease.

Abstract

OBJECTIVE:

Inflammatory bowel disease (IBD) is a chronic intestinal disease. This study was attempted to investigate the effects of long noncoding RNA KIF9-AS1 (KIF9-AS1) on the development of IBD and its underlying mechanism of action.

METHODS:

Quantitative real time PCR (qRT-PCR) was implemented to examine the expression of KIF9-AS1 and microRNA-148a-3p (miR-148a-3p). The IBD mouse model was induced by dextran sulfate sodium (DSS). The body weight, disease activity index (DAI) score, colon length and histological injury were used to evaluate the colon injury. The levels of proinflammatory cytokines were measured by ELISA. In vitro, IBD was simulated by DSS treatment in colonic cells. Then the apoptosis of colonic cells was detected by flow cytometry assay. Furthermore, a dual-luciferase reporter assay was used to demonstrate the interactions among KIF9-AS1, miR-148a-3p and suppressor of cytokine signaling (SOCS3).

RESULTS:

KIF9-AS1 expression was upregulated in IBD patients, DSS-induced IBD mice and DSS-induced colonic cells, whereas miR-148a-3p expression was downregulated. KIF9-AS1 silencing attenuated the apoptosis of DSS-induced colonic cells in vitro and alleviated colon injury and inflammation in DSS-induced IBD mice in vivo. Additionally, the mechanical experiment confirmed that KIF9-AS1 and SOCS3 were both targeted by miR-148a-3p with the complementary binding sites at 3'UTR. Moreover, miR-148a-3p inhibition or SOCS3 overexpression reversed the suppressive effect of KIF9-AS1 silencing on the apoptosis of DSS-induced colonic cells.

CONCLUSION:

KIF9-AS1 silencing hampered the colon injury and inflammation in DSS-induced IBD mice in vivo, and restrained the apoptosis of DSS-induced colonic cells by regulating the miR-148a-3p/SOCS3 axis in vitro, providing a new therapeutic target for IBD.

• Authors: Jun Yao, Ruoyu Gao, Minghan Luo, Defeng Li, Liliangzi Guo, Zichao Yu, Feng Xiong, Cheng Wei, Benhua Wu, Zhenglei Xu, Dingguo Zhang, Jianyao Wang, Lisheng Wang
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 33 Issue 1S Suppl 1 Pg. e922-e932 (12 01 2021) ISSN: 1473-5687 [Electronic] England
• PMID: 34750325 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• Cytokines
• KIF9 protein, human
• Membrane Proteins
• MicroRNAs
• RNA, Long Noncoding
• Kinesins

Topics

• Animals
• Apoptosis (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cytokines
• Humans
• Inflammation
• Inflammatory Bowel Diseases (genetics)
• Kinesins (genetics)
• Membrane Proteins
• Mice
• MicroRNAs (genetics, metabolism)
• RNA, Long Noncoding (genetics, metabolism)