Gastric Cancer Derived Mesenchymal Stem Cells Promote the Migration of Gastric Cancer Cells Through miR-374a-5p

Abstract

Introduction: Resident mesenchymal stem cells (MSCs) in the tumor microenvironment play an important role in tumor progression. Up to now, the mechanism of resident MSCs promoting gastric cancer cell migration remains unclear.

Methods: We tested the migration ability of gastric cancer cells by transwell assays in this study. The inflammatory factors secreted by MSCs were detected by Luminex and ELISA. The activation of NF-κB signaling was detected by western blot. The exosomes derived from MSCs were isolated and identified by transmission electron microscope, nano-sight and western blot. The expression of miR-374a-5p was confirmed by qRT-PCR and its downstream target HAPLN1 by luciferase reporter assay. The expression of adhesion molecules of gastric cancer cells was detected by flow cytometry.

Results: MiR-374a-5p could regulate the expression of inflammatory factors by activating NF-κB signaling. The increase of MCP-1 and the decrease of IFN-γ promoted the migration of gastric cancer cells. The miR-374a-5p in MSCs could be encapsulated and delivered to gastric cancer cells by exosomes derived from MSCs. Exogenous miR-374a-5p up-regulated the expression of adhesion molecules in gastric cancer cells by targeting HAPLN1. And miR-374a-5p-enriched exosomes also promoted the migration of gastric cancer cells.

Conclusion: MiR-374a-5p promoted gastric cancer metastasis, and resident MSCs in the gastric cancer microenvironment played a major role in the regulation of gastric cancer metastasis. The study will provide new ideas and potential targets for the prevention and treatment of gastric cancer metastasis.

Keywords: HAPLN1; Mesenchymal stem cell; gastric cancer; miR-374a-5p; migration; tumor microenvironment.