METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis

被引：0
作者：
Wu, Weiyun [1 ,2 ]
Li, Xiaowen [1 ,2 ]
Zhou, Zhuliang [2 ]
He, Huanjin [2 ]
Pang, Cheng [2 ]
Ye, Shicai [2 ]
Quan, Juan-Hua [1 ,2 ]
机构：
[1] Guangdong Med Univ, Lab Gastroenterol, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China
[2] Guangdong Med Univ, Dept Gastroenterol, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China
来源：
CELL BIOLOGY AND TOXICOLOGY | 2024年 / 40卷 / 01期
关键词：
Ulcerative colitis; M6A modification; METTL14; LncRNA DHRS4-AS1; MiR-206; A3AR;
D O I：
10.1007/s10565-024-09944-8
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated in inflammatory bowel diseases. Methyltransferase-like 14 (METTL14) is the major subunit of the methyltransferase complex catalyzing m6A modifications. Here, we designated to examine the regulatory effects and mechanisms of METTL14 on long non-coding RNA (lncRNA) during UC progression. METTL14 knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP and cleaved Caspase-3 levels, while reducing Bcl-2 levels. METTL14 knockdown also led to a significant increase in NF-kappa B pathway activation and inflammatory cytokine production in the Caco-2 cells treated with TNF-alpha. Moreover, the suppression of METTL14 aggravated colonic damage and inflammation in our dextran sulfate sodium (DSS)-induced murine colitis model. METTL14 silencing suppressed DHRS4-AS1 expression by reducing the m6A modification of DHRS4-AS1 transcripts. Furthermore, DHRS4-AS1 mitigated inflammatory injury by targeting the miR-206/adenosine A3 receptor (A3AR) axis. DHRS4-AS1 overexpression counteracted the enhancing impact of METTL14 knockdown on TNF-alpha-induced inflammatory injury in Caco-2 cells. In conclusion, our findings suggest that METTL14 protects against colonic inflammatory injury in UC via regulating the DHRS4-AS1/miR-206/A3AR axis, thus representing a potential therapeutic target for UC.
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页数：16
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