MicroRNA-34a attenuates the proliferation, invasion and metastasis of gastric cancer cells via downregulation of MET

Abstract

Proliferation, invasion and metastasis are key features of gastric cancer, contributing to high mortality rates in patients with gastric cancer worldwide. As a direct target of p53, the functions of microRNA (miR)-34a are important, but controversial, in the progression of gastric cancer. In the present study, the clinical importance of miR-34a in GC specimens (n=40) were investigated and were confirmed in an independent cohort from The Cancer Genome Atlas (TCGA; n=352). The prognostic value of miR-34a was analyzed using a Kaplan-Meier survival curve in the TCGA cohort, in combination with complete follow-up data (n=157). The level of miR-34a was detected in the human gastric cancer cell line and normal gastric epithelial cell line. The effect of miR-34a on proliferation and invasion were evaluated using Cell Counting Kit 8, colony formation and cell invasion assays. The molecular basis of miR-34a was determined by bioinformatics prediction. The correlation between miR-34a and MET was assessed using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The results indicated that miR-34a was downregulated in the gastric cancer tissues, compared with the normal gastric tissues (P<0.01). miR-34a was negatively correlated with the depth of invasion and lymph node metastasis of gastric cancer (P<0.01). In the TCGA cohort, the levels of miR-34a were lower in T3 and T4 tumor stages, compared with the level in the T1 stage, and low levels of miR-34a predicted significantly longer survival rates in patients with GC (P<0.05). miR-34a also attenuated the proliferation ability, and inhibited the colony formation and cell invasion abilities of the cells (P<0.01). A negative correlation was observed between miR-34a and MET in gastric cancer (P<0.01; r=0.9526), and >60% of cases exhibited consistent expression of miR-34a and MET in gastric cancer (P<0.01). In conclusion, miR-34a was associated with the clinicopathological features of gastric cancer and was a valuable predictor of patient prognosis. miR-34a acted as a tumor suppressor to inhibit gastric cancer proliferation and invasion via the downregulation of MET.