Silencing of miR490-3p by H. pylori activates DARPP-32 and induces resistance to gefitinib.

Infection with Helicobacter pylori (H. pylori) is the main risk factor for gastric carcinogenesis. In this study, we investigated the expression, molecular functions, and downstream effectors of miR490-3p in gastric cancer. We used in vitro and in vivo models to investigate the role of H. pylori in regulating miR490-3p, functions, and therapeutic resistance. Human and mouse neoplastic gastric lesions demonstrated a negative correlation between and miR490-3p expression (R = -0.58, P < 0.01). This was also detected following infection with H. pylori (R = -0.66, P < 0.01). Molecular assays confirmed Dduanyu37P-32 as a direct target of miR490-3p. CHRM2, the host gene of miR490-3p, was hypermethylated and downregulated in neoplastic gastric tissues (P < 0.05). H. pylori induced methylation and downregulation of CHRM2 and miR490-3p. Functionally, the reconstitution of miR490-3p sensitized cancer cells to gefitinib by inactivating DRAPP-32-dependent AKT and pathways. Patients with low miR490-3p or high Dduanyu37P-32 expression had decreased overall survival (P < 0.05). Hypermethylation-mediated silencing of CHRM2 and miR490-3p by H. pylori increased Dduanyu37P-32 expression. Downregulation of miR490-3p in gastric cancer plays a role in gefitinib response by inducing activation of PI3K/AKT, duanyu18133 signaling pathways. Published by Elsevier B.V.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}