miR-199a-3p suppresses progression of esophageal squamous cell carcinoma through inhibiting mTOR/p70S6K pathway

Abstract

Dysregulation of microRNA contributes to multiple tumorigenic processes. Although downregulation of miR-199a-3p has been shown in many cancers, its effects on esophageal squamous cell carcinoma (ESCC) and the regulatory mechanism are still obscure. Here, we aim to evaluate the biological function and underlying mechanisms of miR-199a-3p in ESCC as well as its value to clinical treatment of ESCC. We first analyzed expression of miR-199a-3p in esophageal cancer by bioinformatic analysis and found that there were different opinions about expression of miR-199a-3p in esophageal cancer, and the following qRT-PCR assay demonstrated which was markedly downregulated in ESCC cells. Next, we increased the expression of miR-199a-3p in ESCC cells using miR-199a-3p mimics and demonstrated that overexpression of miR-199a-3p significantly inhibited cell proliferation, migration and invasion, as well as induced cell cycle retard and promoted apoptosis in ESCC. Furthermore, we explored the functional targets of miR-199a-3p and identified that overexpression of miR-199a-3p inhibited mTOR/p70S6K pathway, but stimulated PI3K/Akt pathway. Finally, we demonstrated that overexpression of miR-199a-3p enhanced proliferation-inhibiting effects of MK2206, an inhibitor of Akt, to ESCC cells, which might be related that MK2206 eliminated the activation of miR-199a-3p to p-Akt. These findings discover that miR-199a-3p might participate in the carcinogenesis process of ESCC, which provides a new insight for treatment of ESCC.