MiRNA-219a-1-3p inhibits the malignant progression of gastric cancer and is regulated by DNA methylation

Abstract

Abstract Objective Worldwide, gastric cancer (GC) is one of primary reasons for cancer-related deaths. However, the pathogenic mechanism underlying GC remains to be fully understood. MicroRNAs are momentous regulators of diverse biological progression in cancer. Even though the ability of miR-219a-1-3p to inhibit malignant progression in pancreatic cancer have been previously reported, its role in GC remains to be elucidated. Methods Quantitative real-time PCR (qRT-PCR) was performed to measure miR-219a-1-3p expression levels in collected GC samples (n=98) and paired nearby non-tumor tissues. Cell proliferation, migration, and invasion assays were then conducted to explain the biological influences of miR-219a-1-3p in vitro. In vivo effects were confirmed by subcutaneously injecting miR-219a-1-3p overexpressing MGC-803 cells into nude mice. Methylation-specific PCR was employed to evaluate the CpG island upstream methylation condition of miR-219a-1-3p in collected clinical tissues (n=22), GC cell lines and GES-1 cells. GC cells were supplemented with 5-aza-2′-deoxycytidine to identify the miR-219a-1-3p expression changes using qRT-PCR. Results The miR-219a-1-3p expression was obviously suppressed in GC tissues relation to nearby non-tumor tissues, along with in GC cell lines in comparison to GES-1. Moreover, in vivo and in vitro functional evaluations indicated the function of miR-219a-1-3p in inhibiting the malignant characteristics of GC cells. Mechanistically, MiR-219a-1-3p expression was partly regulated utilizing DNA hypermethylation in GCs. In addition, overexpression of miR-219a-1-3p inhibited PI3K/AKT signaling. Conclusions MiR-219a-1-3p might function as a tumor suppressor in GC, and our investigation creates a foundation to diagnose of GC.