EGFR-ERK signaling pathway down-regulates miRNA-145 in lung cancer cells.
- Author:
Yue-hui GUO
1
;
Feng-hou GAO
;
Jing SHI
;
Hai-hua YUAN
;
Bin JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Butadienes; pharmacology; Carcinoma, Non-Small-Cell Lung; metabolism; pathology; Cell Line; Cell Line, Tumor; Down-Regulation; Enzyme Activation; drug effects; Enzyme Inhibitors; pharmacology; Epidermal Growth Factor; pharmacology; Epithelial Cells; metabolism; Humans; Lung; cytology; Lung Neoplasms; metabolism; pathology; MAP Kinase Signaling System; MicroRNAs; metabolism; Mitogen-Activated Protein Kinase 1; metabolism; Mitogen-Activated Protein Kinase 3; metabolism; Nitriles; pharmacology; Phosphorylation; Quinazolines; pharmacology; Receptor, Epidermal Growth Factor; antagonists & inhibitors; metabolism; Tyrphostins; pharmacology
- From: Chinese Journal of Oncology 2013;35(3):187-192
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the relationship between EGFR activation and down-regulation of miRNA-145 in lung cancer.
METHODSNormal human lung epithelia cell line (BEAS-2B), human lung adenocarcinoma cell lines with wild-type EGFR (A549 and H292) and human lung adenocarcinoma cell lines with EGFR mutation (H1975 and H1650) were chosen in this study. The levels of miRNA-145 and p-EGFR were determined by quantitative real-time PCR (qRT-PCR) and Western blotting, respectively, and the relationship between p-EGFR and miRNA-145 levels was analyzed. The miRNA-145 levels were determined by qRT-PCR after activating EGFR with EGF or blocking EGFR signal pathway with AG1478. In addition, ERK1/2 inhibitor U0126 was used to inhibit ERK1/2 activation and then the expression of miRNA-145 was detected.
RESULTSThe miRNA-145 levels were closely negatively related with p-EGFR in lung cancer cells (r = -0.926, P = 0.024). EGF down-regulated miRNA-145 expression, particularly in BEAS-2B cells (53.0%; t = 30.993, P = 0.001) and A549 cells (42.6%; t = 14.326, P = 0.005).The miRNA-145 was up-regulated after inhibiting p-EGFR with AG1478, and significantly enhanced by 67.5% in H1975 cells when treated with AG1478 (t = 8.269, P = 0.014). The ERK1/2 signal pathway was activated by p-EGFR. U0126 restored the miRNA-145 down-regulation induced by EGFR-activation in lung cancer cells.
CONCLUSIONThe activation of EGFR down-regulates miRNA-145 expression through ERK1/2 in lung cancer cells.
