miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells

Gang Chen, Ijeoma Umelo, Shasha Lv, Erik Teugels, Karel Fostier, Peter Kronenberger, Alex Dewaele, Jan Sadones, Caroline Geers, Jacques De Greve

Onderzoeksoutput: Articlepeer review

241 Citaten (Scopus)

Samenvatting

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-?B 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
Originele taal-2English
Artikelnummere60317
Aantal pagina's13
TijdschriftPLoS ONE
Volume8
Nummer van het tijdschrift3
DOI's
StatusPublished - 2013

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