Identification of Long Non-Coding RNAs Involved in Chronic Inflammation in Helicobacter Pylori Infection and Associated Gastric Carcinogenesis

Abstract

Helicobacter pylori infection and associated chronic gastritis increase the risk for development of gastric cancer (GC). It is desirable to ascertain the precise underlying molecular mechanisms and pathophysiological implications of chronic inflammation and associated carcinogenesis. There is growing evidence that long non-coding RNAs (lncRNAs) play important roles in a wide repertoire of biological processes. It is very likely that lncRNAs also play critical roles in chronic inflammation and carcinogenesis. However, few studies have reported the involvement of lncRNAs in chronic inflammation. In this study, we aimed comprehensively to identify novel lncRNAs critically involved in chronic inflammation and associated carcinogenesis. To search for novel lncRNAs, we used ChIP-seq technology to obtain global histone methylation profiles in gastric epithelial cells. We first compared global histone H3 lysine 4 trimethylation profiles between gastric mucosae with and without active H. pylori infection and then identified lncRNAs associated with H. pylori infection. Next, we compared gastric mucosa from healthy individuals with background mucosa from patients with GC. TCONS_00027118 was identified as a downregulated lncRNA gene in the background mucosa; it was silenced by DNA methylation. Moreover, the methylation of this region was universally observed in various tumours in other organs. In contrast, TCONS_00006264 was identified as an upregulated lncRNA gene. Knockdown of the lncRNA substantially reduced gastric cancer cell viability, suggesting that it has important functions. Here we provide lists of lncRNAs potentially involved in H. pylori infection and gastric carcinogenesis. These lists will be useful resources for further functional and clinical studies.