Abstract 1259: Loss of TFF1 promotes growth and chemotherapeutic resistance in gastric cancer

Background: Downregulation or loss of TFF1 expression occurs in more than half of human gastric adenocarcinomas through gene deletions, mutation, and a loss of heterozygosity or hypermethylation. Our previous studies have shown that Tff1 knockout (KO) in mice induces gastric lesions from low- grade dysplasia (LGD), high- grade dysplasia (HGD) to adenocarcinoma. BRD2, a family member of BET proteins, promotes aberrant gene expression in a variety of malignant tumors. In this study, with the analysis of Tff1 KO mice and human gastric cancer tissue samples, we discovered that loss of Tff1 promotes gastric cancer proliferation and drug resistance through upregulating BRD2 expression level. Methods and Results: Integration Next Generation Sequencing data analysis in both Tff1 KO mice and human gastric cancer tissue samples demonstrated that miR-143-3p was significantly down-regulated in both mice and human gastric cancer samples (P Conclusion: This study unveils, for the first time, loss of TFF1 promotes BRD2 activation in gastric cancer through decreasing miR-143-3p. This axis presents novel therapeutic opportunities by using approaches that reconstitute miR-143-3p or utilizing the recently developed clinical trials in human gastric cancer. Citation Format: Zheng Chen, Zheng Li, Mohammed Soutto, Weizhi Wang, Shoumin Zhu, Alejandro Corvalan, Zekuan Xu, Wael El-Rifai. Loss of TFF1 promotes growth and chemotherapeutic resistance in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1259.