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

被引：10

作者：

Yao, Jun ^{[1
]}

Gao, Ruoyu ^{[1
]}

Luo, Minghan ^{[1
]}

Li, Defeng ^{[1
]}

Guo, Liliangzi ^{[1
]}

Yu, Zichao ^{[1
]}

Xiong, Feng ^{[1
]}

Wei, Cheng ^{[1
]}

Wu, Benhua ^{[1
]}

Xu, Zhenglei ^{[1
]}

Zhang, Dingguo ^{[1
]}

Wang, Jianyao ^{[2
]}

Wang, Lisheng ^{[1
]}

机构：

[1] Jinan Univ, Dept Gastroenterol, Clin Med Sci 2, Shenzhen Municipal Peoples Hosp, 1017,East Gate Rd, Shenzhen, Guangdong, Peoples R China

[2] Shenzhen Childrens Hosp, Dept Gen Surg, Shenzhen, Guangdong, Peoples R China

来源：

EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY | 2021年 / 33卷

基金：

中国国家自然科学基金;

关键词：

apoptosis; inflammatory bowel disease; long noncoding RNA KIF9-AS1; microRNA-148a-3p; suppressor of cytokine signaling; ULCERATIVE-COLITIS; EXPRESSION; PATHOGENESIS; SUPPRESSOR; SOCS3; NOD2;

D O I：

10.1097/MEG.0000000000002309

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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 microRNA148a-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. Copyright (C) 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

引用

页码：E922 / E932

页数：11

共 44 条

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