{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:12:02Z","timestamp":1792102322203,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T00:00:00Z","timestamp":1663459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>N6\u2010methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase\u2010like 3 (METTL3) plays a vital role in multiple cell functions. This study aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Method<\/jats:title><jats:p>The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid\u2010induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR\u201030b\u20105p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss\u2010of\u2010function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR\u201030b\u20105p with PIK3R2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that the METTL3, DGCR8, miR\u201030b\u20105p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid\u2010induced ICCs. Silencing of METTL3 and miR\u201030b\u20105p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid\u2010induced ICCs. Moreover, overexpression of miR\u201030b\u20105p reversed the cytoprotection of METTL3 knockdown in glutamic acid\u2010induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid\u2010induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid\u2010induced ICCs significantly accelerated the maturation of pri\u2010miR\u201030b\u20105p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K\/Akt\/mTOR pathway and ultimately leads to the cell death of STC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid\u2010induced ICCs by interacting with the DGCR8 and successively modulating the miR\u201030b\u20105p\/PIK3R2 axis in an m6A\u2010dependent manner, and METTL3 may be a potential therapeutic target for STC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15994","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T23:53:25Z","timestamp":1662508405000},"page":"2229-2242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["METTL3 contributes to slow transit constipation by regulating miR\u201030b\u20105p\/PIK3R2\/Akt\/mTOR signaling cascade through DGCR8"],"prefix":"10.1111","volume":"37","author":[{"given":"Wen\u2010jing","family":"Gong","sequence":"first","affiliation":[{"name":"General Surgery, Cancer Center, Department of Colorectal Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College)  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Science and Technology Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao\u2010qiong","family":"Dai","sequence":"additional","affiliation":[{"name":"General Surgery, Cancer Center, Department of Colorectal Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College)  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1180-4816","authenticated-orcid":false,"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"General Surgery, Cancer Center, Department of Colorectal Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College)  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-020-06500-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9837384"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12038-021-00212-z"},{"key":"e_1_2_7_5_1","first-page":"5596531","article-title":"Nostoc sphaeroides K\u00fctz polysaccharide improved constipation and promoted intestinal motility in rats","volume":"2021","author":"Liu Y","year":"2021","journal-title":"Evid. 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