{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:04:19Z","timestamp":1791975859846,"version":"4.4.0"},"reference-count":50,"publisher":"BMJ","issue":"10","funder":[{"name":"Major Projects of Ministry of Science and Technology"},{"name":"Shaanxi Foundation for Innovation Team of Science and Technology"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Project of Research and Development Plan of Shaanxi Province"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2018,12,9]]},"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Gastric intestinal metaplasia (IM) is common in the gastric epithelium of patients with chronic atrophic gastritis. CDX2 activation in IM is driven by reflux of bile acids and following chronic inflammation. But the mechanism underlying how bile acids activate CDX2 in gastric epithelium has not been fully explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed microRNA (miRNA) and messenger RNA (mRNA) profiling using microarray in cells treated with bile acids. Data integration of the miRNA\/mRNA profiles with gene ontology (GO) analysis and bioinformatics was performed to detect potential miRNA-mRNA regulatory circuits. Transfection of gastric cancer cell lines with miRNA mimics and inhibitors was used to evaluate their effects on the expression of candidate targets and functions. Immunohistochemistry and in situhybridisation were used to detect the expression of selected miRNAs and their targets in IM tissue microarrays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate a bile acids-triggered pathway involving upregulation of miR-92a-1\u20135p and suppression of its target FOXD1 in gastric cells. We first found that miR-92a-1\u20135p was increased in IM tissues and induced by bile acids. Moreover, miR-92a-1\u20135p was found to activate CDX2 and downstream intestinal markers by targeting FOXD1\/FOXJ1 axis and modulating activation of nuclear factor kappa B (NF-\u03baB) pathway. Furthermore, these effects were found to be clinical relevant, as high miR-92a-1\u20135p levels were correlated with low FOXD1 levels and high CDX2 levels in IM tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest a miR-92a-1\u20135p\/FOXD1\/NF-\u03baB\/CDX2 regulatory axis plays key roles in the generation of IM phenotype from gastric cells. Suppression of miR-92a-1\u20135p and restoration of FOXD1 may be a preventive approach for gastric IM in patients with bile regurgitation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2017-315318","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T17:24:16Z","timestamp":1547227456000},"page":"1751-1763","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["MicroRNA-92a-1\u20135p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia"],"prefix":"10.1136","volume":"68","author":[{"given":"Ting","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi\u2019an, China"},{"name":"Department of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xi\u2019an Jiaotong University, 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