A Long Non-Coding RNA GATA6-AS1 Inhibits Gastric Intestinal Metaplasia through the Wnt/& beta;-Catenin Pathway

作者全名："Xiao, Xiao; Wan, Xiaoqiang; Yang, XiaoFang; Tong, Jin; Zhou, Li; Deng, Lei; Li, Wen; Luo, Jie; Luo, Zhilin; Chen, Jia; Lin, Ling; Guo, Jinjun; Mei, Zhechuan"

作者地址："[Xiao, Xiao; Mei, Zhechuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400010, Peoples R China; [Xiao, Xiao; Wan, Xiaoqiang; Yang, XiaoFang; Tong, Jin; Zhou, Li; Deng, Lei; Li, Wen; Luo, Zhilin; Chen, Jia] Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Dept Gastroenterol, Chongqing 400010, Peoples R China; [Luo, Jie] Chongqing Univ, Canc Hosp, Chongqing Key Lab Intelligent Diag, Chongqing 400030, Peoples R China; [Lin, Ling] Chongqing Univ, Chongqing Emergency Med Ctr, Cent Lab, Cent Hosp, Chongqing 400010, Peoples R China; [Lin, Ling] Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Chongqing Key Lab Emergency Med, Chongqing 400010, Peoples R China; [Guo, Jinjun] Chongqing Med Univ, Bishan Hosp Chongqing, Bishan Hosp, Dept Gastroenterol, Chongqing 402760, Peoples R China"

通信作者："Mei, ZC (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400010, Peoples R China.; Guo, JJ (通讯作者)，Chongqing Med Univ, Bishan Hosp Chongqing, Bishan Hosp, Dept Gastroenterol, Chongqing 402760, Peoples R China."

来源：JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001016532100001

JCR分区：Q4

影响因子：3.2

年份：2023

卷号：37

期号：5

开始页：2663

结束页：2677

文献类型：Article

关键词：GATA6-AS1; RNA-seq; WGCNA; intestinal metaplasia; the malignant transformation process

摘要："Objective: The Correa cascade explains the histopathological process of gastric carcinogenesis, including chronic non-atrophic gastritis (CNAG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia and gastric cancer (GC). IM is consid-ered as a precancerous lesion of gastric cancer. Therefore, we aimed to identify stratification markers from IM that could predict GC occurrence and explore the mechanism of precancerous lesions.Methods: Whole-transcriptome sequencing (RNA-seq) was performed on 18 clinical gastric mucosal specimens from CNAG, CAG, IM, and GC. Based on weighted gene co-expression network analysis (WGCNA), key modules negatively related to the malignant transformation process were identified and hub genes were found. Expression of candidate lncRNAs (long non-coding RNAs) in human gastric tissues was detected by qRT-PCR (quantitative real-time polymerase chain reaction). Human gastric cell lines GES-1 were treated with chenodeoxycholic acid (CDCA). The GATA6-AS1 (GATA6 antisense RNA 1) overexpression vector and antisense oligonucleotides (ASO) were transfected into gastric cell lines and gastric cancer cell lines, respectively, and qRT-PCR and Western blotting evaluated their effects on the expression of IM markers and the Wnt/& beta;-catenin pathway markers. Results: We constructed a hub gene and lncRNAs co-expression network and identified three candidate lncRNAs with the highest connectivity. The expression of GATA6-AS1 was markedly reduced in the IM group and further decreased in the GC group compared with the CNAG group. According to studies in vitro, GATA6-AS1 exhibited negative regulation of intestinal-specific transcription factor CDX2 (Caudal Type Homeobox 2) and its downstream IM marker KLF4 (kruppel-like factor 4) and MUC2 (mouse polyclonal mucin 2), as well as Wnt signaling pathway markers in GES-1 (The human normal gastric epithelial cell line) and SGC7901 cell lines. Furthermore, the overexpressed GATA6-AS1 could reverse CDCA-induced high expression of IM markers and inhibit Wnt signaling pathway marker.Conclusions: GATA6-AS1 possibly serves as the potential marker for IM and could reduce the expression of intestinal metaplasia markers by inhibiting the Wnt signaling pathway, thereby inhibiting the occurrence of IM and intestinal-type gastric cancer."

基金机构：Chongqing Science and Technology Innovation [cstc2019jscx-msxmX0202]; Joint Project of Chongqing Health Commission and Science and Technology Bureau [2020FYYX084]; Scientific Research Project of the National Natural Science Foundation of China [82173360]

基金资助正文："This research was supported by grants from Chongqing Science and Technology Innovation and Application Development Project (cstc2019jscx-msxmX0202), the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2020FYYX084), the Scientific Research Project of the National Natural Science Foundation of China (82173360)."