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Non-small cell lung cancer (NSCLC) is the first cause of cancer related death in the world. Biomarkers to predict the relapse and drug resistance could be extremely useful for a clinical doctor to monitor high risk patients and select rational regimen. miRNAs play an important role in lung cancer and detection samples are relatively easy to be obtained, miRNAs could become a promising means of comprehending the oncogenesis and pathogenesis of lung cancer. This study aimed to investigate the function of miR-145 to work as a biomarker in NSCLC. miR-145 expression level in 48 NSCLC tumor tissues and their matched normal tissues were detected by qRT-PCR. miR-145 in 18 paraffin-embedded samples underwent chemotherapy and were assessed by in situ hybridization (ISH). Here we show that miR-145 was down-regulated in NSCLC tissues; down-regulation of miR-145 was correlated with late clinical stage and poorly differentiated carcinoma, and, low expression level of miR-145 could also predict chemotherapy resistance and shorter disease-free survival (DFS). These findings indicated that miR-145 expression may be a useful prognostic marker that could be used for predicting poor differentiation, chemo-resistance and shore DFS. [ABSTRACT FROM AUTHOR]

Abstract: Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), namely, gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. About 50% of this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as the one corresponding to T790M. In our previous study, we found that combined treatment with fulvestrant and gefitinib decreases the proliferation of H1975 NSCLC cells, compared to treatment with either fulvestrant or gefitinib alone; however, the molecular mechanism for the improved effects of the combination treatment are still unknown. In this study, we confirmed that fulvestrant increases the gefitinib sensitivity of H1975 cells and found that let-7c was most upregulated in the fulvestrant-treated cells. Our data revealed that let-7c increases gefitinib sensitivity by repressing RAS and inactivating the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways. Taken together, our findings suggest that let-7c plays an important role in fulvestrant-induced upregulation of gefitinib sensitivity in H1975 cells. [Copyright &y& Elsevier]