title: 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.
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.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, P.R. China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, P.R. China.
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Jiang
authors.affiliation: Department of Prosthodontics, Second Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, P.R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, P.R. China.
authors.forename: Yu-Na
authors.initials: YN
authors.lastname: Tong
authors.affiliation: Department of Internal Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, P.R. China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Liu
mesh_terms: D000368:Aged; D017209:Apoptosis; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011836:Radiation Tolerance; D015854:Up-Regulation
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: APOPTOSIS; EGFR; ESOPHAGEAL CANCER; MEK/ERK; MicroRNA-133a; RADIO-SENSITIVITY; SIGNALING PATHWAY