miR-337-3p suppresses the proliferation and invasion of hepatocellular carcinoma cells through targeting JAK2

Am J Cancer Res. 2018 Apr 1;8(4):662-674. eCollection 2018.

Abstract

Accumulating evidence has indicated that microRNA (miRNA) dysregulation contributes to hepatocellular carcinoma (HCC) progression. miR-337-3p is downregulated in gastric cancer and neuroblastoma; however, its biological function and underlying mechanism in HCC remain unclear. In this study, we showed that the expression level of miR-337-3p was significantly decreased in HCC, and was associated with several clinicopathological characteristics, including tumor multiplicity, histological differentiation, and Barcelona Clinic Liver Cancer stage. Low expression level of miR-337-3p was associated with poor survival outcomes in HCC patients. Upregulation of miR-337-3p suppressed cell proliferation, migration, and invasion in HCC. Dual luciferase assay demonstrated that JAK2 was a direct downstream target of miR-337-3p. JAK2 reintroduction restored the inhibited proliferation, migration, and invasion of miR-337-3p overexpressed HCC cells. miR-337-3p functioned as a tumor suppressor to modulate the JAK2/STAT3 signaling pathway. The present findings indicate that miR-337-3p could be used as a prognostic predictor and therapeutic candidate for HCC.

Keywords: Hepatocellular carcinoma; JAK2; invasion; miR-337-3p; proliferation.