NORAD-sponged miR-378c alleviates malignant behaviors of stomach adenocarcinoma via targeting NRP1.

ABSTRACT

BACKGROUND: Stomach adenocarcinoma (STAD) is the most common type of gastric cancer (GC), with a high recurrence rate and poor prognosis, but the potential indicators for STAD are insufficient. METHODS: Herein, we found that MicroRNA-378c (miR-378c) was lowly expressed in STAD, and the low expression of miR-378c was highly correlated with poor overall survival (OS), T stage, Reflux history, DSS events and PFI events of STAD patients. RESULTS: In addition, univariate analysis displayed that miR-378c was significantly associated with OS (Hazard ratio 0.735; 95% CI, 0.542-0.995; P = 0.046). Furthermore, it was validated that miR-378c inhibition accelerated STAD cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), while they were suppressed by miR-378c overexpression. Mechanistically, Neuropilin 1 (NRP1) was confirmed as the target of miR-378c, and Lnc-NORAD was identified as its sponger. More importantly, NORAD-mediated miR-378c inhibited malignant behaviors of STAD both in vitro and in vivo. CONCLUSIONS: Collectively, these results suggest miR-378c as a promising indicator for the treatment of STAD.