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Ectopic expression of HNF4\u03b1 was observed in a BA-induced IM cell model. However, the mechanisms underlying the upregulation of the protein in IM cells remains to be elucidated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The effects of HNF4\u03b1 on gastric mucosal cells in vivo were identified by a transgenic mouse model and RNA-seq was used to screen downstream targets of deoxycholic acid (DCA). The expression of pivotal molecules and miR-1 was detected by immunohistochemistry and in situ hybridization in normal, gastritis and IM tissue slides or microarrays. The transcriptional regulation of HDAC6 was investigated by chromatin immunoprecipitation (ChIP) and luciferase reporter assays.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The transgenic mouse model validated that HNF4\u03b1 stimulated the HDAC6 expression and mucin secretion in gastric mucosa. Increased HDAC6 and HNF4\u03b1 expression was also detected in the gastric IM cell model and patient specimens. HNF4\u03b1 could bind to and activate HDAC6 promoter. In turn, HDAC6 enhanced the HNF4\u03b1 protein level in GES-1 cells. Furthermore, miR-1 suppressed the expression of downstream intestinal markers by targeting HDAC6 and HNF4\u03b1.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings show that the HDAC6\/HNF4\u03b1 loop regulated by miR-1 plays a critical role in gastric IM. Blocking the activation of this loop could be a potential approach to preventing BA-induced gastric IM or even gastric cancer (GC).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10120-020-01108-x","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T20:02:47Z","timestamp":1595534567000},"page":"103-116","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["HDAC6\/HNF4\u03b1 loop mediated by miR-1 promotes bile acids-induced gastric intestinal metaplasia"],"prefix":"10.1007","volume":"24","author":[{"given":"Na","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoxia","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siran","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-7577","authenticated-orcid":false,"given":"Yongquan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"1108_CR1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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