Downregulation miR-539 is associated with poor prognosis of gastric cancer patients and aggressive progression of gastric cancer cells.

Abstract

miR-539 functions as a tumor suppressor in many types of cancer. However, the role of miR-539 in gastric cancer remains unclear. The aim of this study is to investigate the clinical significance and functional role of miR-539 in gastric cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-539 in gastric cancer patients tissues and cells. We analyzed the association between miR-539 expression levels and clinicopathological features, as well as overall survival information with Kaplan-Meier survival curves and Cox regression analysis. The functional role of miR-935 on the proliferation, migration, and invasion was also investigated by using miR-539 mimic or miR-539 inhibitor through CCK-8 assay, Transwell migration and invasion assays. The relationship between miR-539 and RUNX2 was verified by a dual luciferase assay. The expression of miR-539 was decreased in gastric cancer tissues and cell lines. Downregulation of miR-539 was closely associated with differentiation, lymph node metastasis, TNM stage, and poor survival outcome of gastric cancer patients. Furthermore, overexpression of miR-539 inhibited cell proliferation, migration, and invasion of gastric cancer cells. In addition, RUNX2 was a direct target of miR-539. Taken together, miR-539 may serve as a tumor suppressor for inhibiting cell proliferation, migration, and invasion by targeting RUNX2. Reduced expression of miR-539 is an independent prognostic factor in gastric cancer and may be a potential prognostic biomarker and miR-539/RUNX2 axis may serve as a potential therapeutic target for the treatment of gastric cancer.