Helicobacter pylori induces caudal-type homeobox protein 2 and cyclooxygenase 2 expression by modulating microRNAs in esophageal epithelial cells.
Helicobacter pylori induces caudal-type homeobox protein 2 and cyclooxygenase 2 expression by modulating microRNAs in esophageal epithelial cells.
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幽门螺杆菌通过调节食管上皮细胞中的 microRNA 来诱导尾部型同源盒蛋白 2 和环氧合酶 2 的表达。
DOI：
10.1111/cas.13462
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发表时间：
2018-03
期刊：
影响因子：
5.7
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Teng G;Dai Y;Chu Y;Li J;Zhang H;Wu T;Shuai X;Wang W
microRNAs（miRNAs）的失调与幽门螺杆菌的毒力因子有关。幽门螺杆菌在食管疾病中的作用尚未明确。我们以前曾报道过幽门螺杆菌在食管的定植促进了Barrett食管和食管腺癌的发生。在这里，我们研究了幽门螺杆菌对食管上皮细胞转化的直接影响，特别关注幽门螺杆菌是否通过调节miRNA及其下游靶基因发挥其作用。正常人食管细胞系HET-1A长期暴露于幽门螺杆菌提取物和/或酸化脱氧胆酸长达36周。通过基因芯片分析确定与幽门螺杆菌感染相关的食管上皮细胞的miRNA谱。我们发现，慢性幽门螺杆菌暴露促进了酸化脱氧胆酸诱导的HET-1A细胞形态学变化，沿着肠上皮化生标志物和致瘤因子的异常过表达，包括尾型同源框蛋白2（CDX 2）、粘蛋白2和环氧合酶2（COX 2）。幽门螺杆菌改变了食管上皮细胞的miRNA谱，特别是miR-212 - 3 p和miR-361 - 3 p的异常沉默。此外，在Barrett食管患者的活检中，食管幽门螺杆菌定植与miR-212 - 3 p和miR-361 - 3 p表达显著降低相关。此外，我们将COX 2鉴定为miR-212 - 3 p的靶点，将CDX 2鉴定为miR-361 - 3 p的靶点。食管上皮细胞的幽门螺杆菌感染与miRNA介导的癌蛋白CDX 2和COX 2上调相关。我们的观察为幽门螺杆菌感染与食管癌发生之间的分子机制提供了新的证据。
Dysregulation of microRNAs (miRNAs) has been linked to virulence factors of Helicobacter pylori. The role of H. pylori in esophageal disease has not been clearly defined. We previously reported that H. pylori esophageal colonization promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in vivo. Here, we studied the direct effects of H. pylori on the transformation of esophageal epithelial cells, with particular focus on whether H. pylori exerts its effects by modulating miRNAs and their downstream target genes. The normal human esophageal cell line HET‐1A was chronically exposed to H. pylori extract and/or acidified deoxycholic acid for up to 36 weeks. The miRNA profiles of the esophageal epithelial cells associated with H. pylori infection were determined by microarray analysis. We found that chronic H. pylori exposure promoted acidified deoxycholic acid‐induced morphological changes in HET‐1A cells, along with aberrant overexpression of intestinal metaplasia markers and tumorigenic factors, including caudal‐type homeobox protein 2 (CDX2), mucin 2, and cyclooxygenase 2 (COX2). Helicobacter pylori modified the miRNA profiles of esophageal epithelial cells, particularly aberrant silencing of miR‐212‐3p and miR‐361‐3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal H. pylori colonization was associated with a significant decrease in miR‐212‐3p and miR‐361‐3p expression. Furthermore, we identified COX2 as a target of miR‐212‐3p, and CDX2 as a target of miR‐361‐3p. Helicobacter pylori infection of esophageal epithelial cells was associated with miRNA‐mediated upregulation of oncoprotein CDX2 and COX2. Our observations provide new evidence about the molecular mechanisms underlying the association between H. pylori infection and esophageal carcinogenesis.
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影响因子：
4.4
作者：
Fischbach LA;Nordenstedt H;Kramer JR;Gandhi S;Dick-Onuoha S;Lewis A;El-Serag HB
通讯作者：
El-Serag HB
影响因子：
9.8
作者：
Correa, Pelayo;Piazuelo, M. Blanca;Wilson, Keith T.
通讯作者：
Wilson, Keith T.
影响因子：
6.4
作者：
Matsushima, Kayoko;Isomoto, Hajime;Kohno, Shigeru
通讯作者：
Kohno, Shigeru
影响因子：
4.4
作者：
Liu, Fang-Xun;Wang, Wei-Hong;Gao, Pei-Pei
通讯作者：
Gao, Pei-Pei
影响因子：
3.3
作者：
DiMaio, Michael A.;Kwok, Shirley;Pai, Reetesh K.
通讯作者：
Pai, Reetesh K.