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Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)\u201027a\u20103p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR\u201027a\u20103p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR\u201027a\u20103p regulates intestinal cell differentiation and proliferation at least in part through the regulation of retinoic acid receptor \u03b1 (RXR\u03b1), a modulator of Wnt\/\u03b2\u2010catenin signalling. Repression of miR\u201027a\u20103p increases the expression of RXR\u03b1 and concomitantly, decreases the expression of active \u03b2\u2010catenin and cyclin D1. In contrast, overexpression of miR\u201027a\u20103p mimic decreases the expression of RXR\u03b1 and increases the expression of active \u03b2\u2010catenin and cyclin D1. Moreover, overexpression of the miR\u201027a\u20103p mimic results in impaired enterocyte differentiation and increases intestinal epithelial cell proliferation. These alterations were attenuated or blocked by Wnt inhibition. Our study demonstrates an miR\u201027a\u20103p\/RXR\u03b1\/Wnt\/\u03b2\u2010catenin pathway that is important for the maintenance of enterocyte homeostasis in the small intestine.<\/jats:p>","DOI":"10.1111\/cpr.13757","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T10:26:03Z","timestamp":1727432763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["miR\u201027a\u20103p regulates intestinal cell proliferation and differentiation through Wnt\/\u03b2\u2010catenin signalling"],"prefix":"10.1111","volume":"58","author":[{"given":"Chang","family":"Li","sequence":"first","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuning","family":"Zhou","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinping","family":"Jiang","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Yin","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi L.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingding","family":"Wang","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"},{"name":"Department of Surgery University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-2342","authenticated-orcid":false,"given":"B. Mark","family":"Evers","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky  Lexington Kentucky USA"},{"name":"Department of Surgery University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.08.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2819154"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.08.016"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9074601"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181e913c2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.11.006"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5150869"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otaa003"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-024-00510-2"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2023065"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.04.065"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03022-12"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.267103"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.287404"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2806"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03319"},{"key":"e_1_2_11_21_1","first-page":"43","article-title":"SIRT2 contributes to the regulation of intestinal cell proliferation and differentiation. 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