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.

miR-181a modulates acute myeloid leukemia susceptibility to natural killer cells

“…Our findings further indicate that inhibition of miR-181a in leukemia cells impacted their susceptibility to NKmediated lysis. Although emerging studies indicate the potential involvement of miR-146a in cell proliferation and drug resistance, 44,45 blocking miR-146a in our experimental model had no effect on NK-cell mediated lysis. Therefore, we hypothesized that miR-146a is involved in the molecular mechanisms that contribute to drug resistance but not to resistance to NK-mediated lysis.…”

Expression of Tumor Necrosis Factor Receptor-associated Factor 6 in Lung Cancer Tissues

“…Our group previously found that TRAF6 functions as a bridge between miR-146a and the NF-kB pathway in NSCLC (Chen et al, 2013c). Besides miR-146a, TRAF6 has been proved to be the target genes for miR-125a (Guo et al, 2014) and miR-125b (Wang et al, 2014).…”

“…In China, lung cancer is the first leading cause of death from all cancers (Chen et al,additional therapy. However, the specific markers have not been achievable (Chen et al, 2012;Chen et al, 2013a;2013b;2013c;Gazala et al, 2013;Granger et al, 2013). Therefore, the research for effective molecular markers for diagnosis and treatment of lung cancer is an important issue at present.…”

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

“…Nonsmall cell lung cancers are the most common variety, accounting for 80%‐85% of new LC cases. Approximately, 70% of NSCLCs patients are diagnosed at an advanced stage with the tumor already being metastasized and its 5‐year survival rate is about 16% 9. Therefore, it is urgent to explore the exact molecular processes involved in the development of NSCLCs and to achieve potential therapeutic targets.…”