HDAC6/HNF4α loop mediated by miR-1 promotes bile acids-induced gastric intestinal metaplasia.
HDAC6/HNF4α loop mediated by miR-1 promotes bile acids-induced gastric intestinal metaplasia.
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miR-1 介导的 HDAC6/HNF4α 环促进胆汁酸诱导的胃肠化生
DOI：
10.1007/s10120-020-01108-x
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Wang N;Chen M;Ni Z;Li T;Zeng J;Lu G;Wang J;Zhang J;Wu S;Shi Y
Gastric intestinal metaplasia (IM) is considered a precancerous lesion, and bile acids (BA) play a critical role in the induction of IM. Ectopic expression of HNF4α 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. The effects of HNF4α 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. The transgenic mouse model validated that HNF4α stimulated the HDAC6 expression and mucin secretion in gastric mucosa. Increased HDAC6 and HNF4α expression was also detected in the gastric IM cell model and patient specimens. HNF4α could bind to and activate HDAC6 promoter. In turn, HDAC6 enhanced the HNF4α protein level in GES-1 cells. Furthermore, miR-1 suppressed the expression of downstream intestinal markers by targeting HDAC6 and HNF4α. Our findings show that the HDAC6/HNF4α 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). The online version of this article (10.1007/s10120-020-01108-x) contains supplementary material, which is available to authorized users.
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影响因子：
3.4
作者：
Shimizu T;Seto T;Hirai F;Takenoyama M;Nosaki K;Tsurutani J;Kaneda H;Iwasa T;Kawakami H;Noguchi K;Shimamoto T;Nakagawa K
通讯作者：
Nakagawa K
影响因子：
3.8
作者：
Salemi LM;Maitland MER;Yefet ER;Schild-Poulter C
通讯作者：
Schild-Poulter C
影响因子：
19
作者：
Aoyagi, S;Archer, TK
通讯作者：
Archer, TK
转移性黑色素瘤的临床特征和预后指标：来自华北地区446例患者的数据
影响因子：
--
作者：
Hao, Mengze;Zhao, Gang;Yang, Jilong
通讯作者：
Yang, Jilong
DOI：
10.1152/ajpgi.2000.278.6.g1000
发表时间：
2000-06-01
影响因子：
4.5
作者：
Kaur, BS;Ouatu-Lascar, R;Triadafilopoulos, G
通讯作者：
Triadafilopoulos, G