MiR-613 suppresses migration and invasion in esophageal squamous cell carcinoma via the targeting of G6PD.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and has a high mortality rate. MicroRNAs (miRs) are a family of post-transcriptional regulators, which negatively regulate target gene expression. miR-613 has been revealed to be a diagnostic and prognostic biomarker in ESCC. However, the role of miR-613 in ESCC remains unclear. In the present study, miR-613 expression was identified to be reduced in tumor tissues in comparison with corresponding adjacent normal tissues. TargetScan and a dual-luciferase reporter assay verified glucose-6-phosphate dehydrogenase (G6PD) as a direct target of miR-613. In contrast with miR-613, G6PD expression was increased in tumor tissues compared with matched healthy tissues. Furthermore, overexpression of miR-613 inhibited cell migration and invasion of Eca109 cells compared with controls, while G6PD overexpression reversed the inhibition induced by miR-613, as determined by wound healing and Transwell assays. In addition, miR-613 overexpression decreased the mRNA and protein expression of G6PD, matrix metalloproteinase (MMP)2 and MMP9, and reduced the phosphorylation of signal transducer and activator of transcription 3 (STAT3) compared with controls, while G6PD reversed the effects of miR-613. However, miR-613 and G6PD did not affect the expression of STAT3. In conclusion, the aforementioned results suggest that miR-613 targets G6PD to suppress ESCC cell migration and invasion through reduced MMP2 and MMP9 expression and inactivation of the STAT3 signaling pathway. Thus, the present study may provide a new molecular foundation for treatment of ESCC.