title: miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.
abstract: Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab). These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-κB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE) lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (P<0.05). The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC. Thus inducing miR-146a might be a therapeutic strategy for NSCLC.
authors.affiliation: Department of Pathology, First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Ijeoma Adaku
authors.initials: IA
authors.lastname: Umelo
authors.forename: Shasha
authors.initials: S
authors.lastname: Lv
authors.forename: Erik
authors.initials: E
authors.lastname: Teugels
authors.forename: Karel
authors.initials: K
authors.lastname: Fostier
authors.forename: Peter
authors.initials: P
authors.lastname: Kronenberger
authors.forename: Alex
authors.initials: A
authors.lastname: Dewaele
authors.forename: Jan
authors.initials: J
authors.lastname: Sadones
authors.forename: Caroline
authors.initials: C
authors.lastname: Geers
authors.forename: Jacques
authors.initials: J
authors.lastname: De Grève
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D066246:ErbB Receptors; D000068818:Cetuximab
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