title: Abnormal activation of the EGFR signaling pathway mediates the downregulation of miR‑145 through the ERK1/2 in non-small cell lung cancer.
abstract: The expression of miR-145 with tumor suppressor function is decreased in lung cancer cells. Epidermal growth factor receptor (EGFR) signaling pathway is abnormally activated in lung cancer cells. It is not clear whether the EGFR signaling pathway is involved in the regulation of miR-145 expression in lung cancer. In the present study, we found that the reduction of miR-145 was associated with EGFR abnormal activation in lung cancer cells. AG1478, an inhibitor of EGFR, may restore the expression of miR-145, indicating that EGFR activation is involved in the downregulation of miR-145 in lung cancer cells. Then, the application of STAT3, AKT and ERK1/2 inhibitors and siRNA against these signaling molecules indicated that ERK1/2 or AKT instead of STAT3 was involved in the process of miR-145 downregulation by EGFR. It was confirmed that AKT through activation of the ERK1/2 signaling molecules mediated the effect of EGFR on miR-145. Furthermore, we found that EGFR downregulated miR-145 through ERK1/2 in lung cancer cells. These findings establish EGFR and miR-145 links in lung cancer cells and therefore contribute to a better understanding of the role of EGFR in lung cancer cells, and provide clues for in-depth study of miR-145 expression and a possible direction for the further increase of miR-145 in lung cancer cells.
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Yue-Hui
authors.initials: YH
authors.lastname: Guo
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Central Laboratory, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Mang-Hua
authors.initials: MH
authors.lastname: Xu
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Jiong-Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Central Laboratory, Shanghai Third People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201900, P.R. China.
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D035683:MicroRNAs / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C512478:EGFR protein, human; D066246:ErbB Receptors