The expression and function of miR-376a-3p/DLX axis in gastric cancer cells

Gastric cancer(GC)was referred to a malignant tumor of the digestive tract originating from the epithelium of gastric mucosa.Transcription factor DLX5 was verified as an oncogene in various types of tumors,while miR-376a-3p was speculated as a tumor suppressor.Based on the bioinformatics database,we hypothesized that miR-376a participated in the regulation of GC development by targeting DLX5.Compared with adjacent tissue,a significant increase of DLX5 expression was determined in GC tissues,but the expression level is significantly reduced in miR-376a.Similar expression signature of DLX5 and miR-376a was also determined between 4 GC cells(HGC,SGC,MGC,and AGS cell lines)and GES cell line.The level of DLX5 was notably reduced in HGC and MGC cell lines after miR-376a-3p overexpression,and increased after miR-376a-3p inhibition.Then,the inhibition role of miR-376a-3p on DLX5 was further proved by dualluciferase reporter assay.Gain-of-function experiments showed that upregulation of miR-376a-3p in GC cells could inhibit the ability of epithelial-mesenchymal transition,proliferation,and invasion,and enhance the GC cell apoptosis level.However,these roles of miR-376a-3p could be abolished by DLX5 overexpression.This study confirmed that reduction of miR-376a-3p expression level in GC cells would lead to the increase in cell growth and invasion,indicating that upregulation of miR-376a-3p might have a potential therapeutic role on GC.