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

被引:34
作者
Yang, Qing-Shan [1 ]
Jiang, Li-Peng [1 ]
He, Chun-Yan [2 ]
Tong, Yu-Na [1 ]
Liu, Yuan-Yuan [3 ]
机构
[1] Jinzhou Med Univ, Affiliated Hosp 2, Dept Radiat Oncol, Jinzhou 121001, Peoples R China
[2] Liaoning Med Univ, Affiliated Hosp 2, Dept Prosthodont, Jinzhou 121000, Peoples R China
[3] Jinzhou Med Univ, Dept Internal Neurol, Affiliated Hosp 1, 2 Sect 5 Renmin Rd, Jinzhou 121001, Liaoning Provin, Peoples R China
关键词
MicroRNA-133a; EGFR; MEK/ERK; SIGNALING PATHWAY; ESOPHAGEAL CANCER; RADIO-SENSITIVITY; APOPTOSIS; RADIATION SENSITIVITY; MIR-133A SUPPRESSES; BREAST-CANCER; POOR SURVIVAL; PROLIFERATION; GROWTH; EXPRESSION; MIGRATION; INVASION; FSCN1;
D O I
10.1002/jcb.25829
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2016 Wiley Periodicals, Inc.
引用
收藏
页码:2625 / 2634
页数:10
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