Up‐Regulation of MicroRNA‐133a Inhibits the MEK/ERK Signaling Pathway to Promote Cell Apoptosis and Enhance Radio‐Sensitivity by Targeting EGFR in Esophageal Cancer In Vivo and In Vitro

摘要

ABSTRACT This study aims to explore how microRNA‐133a (miR‐133a) affects cell apoptosis and radio‐sensitivity by targeting EGFR via regulating MEK/ERK pathway in esophageal cancer (EC). A total of 358 EC patients were selected and assigned into the resistant and sensitive groups. Human EC KYSE 150 cell line was assigned into the blank, negative control (NC), miR‐133a mimic, miR‐133a inhibitors, si‐EGFR, miR‐133a inhibitors?+?si‐EGFR groups after transfection. MiR‐133a and EGFR mRNA expressions were detected by qRT‐PCR and EGFR, MEK/ERK pathway‐related protein expressions were detected by Western blotting. The radio‐sensitivity and cell apoptosis were testified by clone formation and flow cytometry. MiR‐133a was up‐regulated but EGFR was down‐regulated in the sensitive group than in the resistant group. Compared with the blank and NC groups, the miR‐133a mimic and si‐EGFR groups exhibited increased cell apoptosis rate but decreased EGFR, p‐MEK1/2, and p‐ERK1/2 protein expressions; while opposite trend was observed in the miR‐133a inhibitors group. Compared with the miR‐133a inhibitors group, the miR‐133a inhibitors?+?si‐EGFR group presented reduced cell survival rate, EGFR, p‐MEK1/2, and p‐ERK1/2 protein expressions but increased cell apoptosis rate. These results indicated that miR‐133a could inhibit the MEK/ERK pathway to promote cell apoptosis and enhance radio‐sensitivity by targeting EGFR in EC. J. Cell. Biochem. 118: 2625–2634, 2017. ? 2017 Wiley Periodicals, Inc.