miR-374a-5p: A New Target for Diagnosis and Drug Resistance Therapy in Gastric Cancer

Mol Ther Nucleic Acids. 2019 Dec 6;18:320-331. doi: 10.1016/j.omtn.2019.07.025. Epub 2019 Aug 27.


Chemoresistance is one of the causes associated with poor prognosis in gastric cancer. MicroRNAs (miRNAs) are important regulators of chemoresistance. Exosome-mediated delivery of anti-cancer molecules and drugs have emerged as a new approach for cancer therapy. We first examined the expression of miR-374a-5p in gastric cancer serum by qRT-PCR and explored the clinicopathological parameters. We then performed in vitro cell and molecular studies, including CCK-8 assay, flow cytometry, qRT-PCR, and western blot, to determine the roles of miR-374a-5p in gastric cancer chemoresistance and identified its downstream target by luciferase reporter assay. We also used in vivo animal studies to evaluate the therapeutic efficacy of miR-374a-5p inhibitor and exosome-mediated delivery of miR-374a-5p inhibitor in gastric cancer. miR-374a-5p expression level was elevated in gastric cancer serum, and its upregulation predicted poor prognosis. miR-374a-5p overexpression promoted while miR-374a-5p knockdown inhibited gastric cancer chemoresistance in vitro and in vivo. miR-374a-5p bound to Neurod1 to antagonize its effect on chemoresistance. Exosome-mediated delivery of miR-374a-5p inhibitor could increase Neurod1 expression, promote cell apoptosis, and suppress chemoresistance. miR-374a-5p had a promoting role in gastric cancer chemoresistance, which would provide a novel biomarker for gastric cancer diagnosis and prognosis and offer a potential target for gastric cancer drug resistance therapy.

Keywords: chemoresistance; exosome; gastric cancer; miR-374a-5p.