Abstract
BackgroundMicroRNAs (miRNAs) have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC). Here, we investigated the role of miR-145 and miR-497 in TGF-β-induced epithelial–mesenchymal transition (EMT) process of NSCLC.MethodsWe performed quantitative real time PCR (qRT-PCR) to detect the expression level of miR-145 and miR-497 in NSCLC cell lines. Then in the presence/absence of TGF-β, we transfected miRNA mimics or inhibitor into A549 and H1299 cells and investigated the role of miR-145 and miR-497 in cell migration and invasion using transwell and wound-healing assay. The regulation role of miR-145 and miR-497 on Metadherin (MTDH) was determined by luciferase assay. The expression level of MTDH and EMT markers E-cadherin and vimentin were detected on mRNA and protein level.ResultsIn our study, our results showed that miR-145 and miR-497 were downregulated in NSCLC cell lines. Overexpression of miR-145 and miR-497 inhibited TGF-β-induced EMT and suppressed cancer cell migration and invasion, while the opposite results were observed in cells transfected with miR-145 or miR-497 inhibitor. Moreover, the luciferase assay confirmed that miR-145 and miR-497 attenuated MTDH expression by directly binding 3′-UTR of MTDH mRNA and exert the tumor-suppression role.ConclusionsOverall, we demonstrated that miR-145 and miR-497 functioned as EMT-suppressor in NSCLC by targeting MTDH, provided new evidence that miR-145 and miR-497 as potential therapeutic targets.
Highlights
MicroRNAs have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC)
Results miR‐145 and miR‐497 are downregulated in NSCLC cell lines The expression levels of miR-145 and miR-497 in three NSCLC cell lines (A549, H1299 and H358) and human bronchial epithelial cell line (HBE) cell line were detected
Compared with HBE, miR-145 and miR-497 decreased in all the NSCLC cell lines (Fig. 1a, b)
Summary
MicroRNAs (miRNAs) have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC). The majority (79%) of non-small cell lung cancer (NSCLC) patients develop metastases from their primary tumor [1]. MTDH is upregulated in multiple cancer tissues and cell lines, induce EMT via oncogenic signaling pathways including PI3 K/Akt, ERK, Wnt/β-catenin signaling, enhance tumor metastasis [11,12,13,14]. Elevated MTDH expression correlated with increased NSCLC proliferation and metastasis and predicted worse prognosis in patients [15,16,17]. These results demonstrated that MTDH may act as an important metastasis promoter in cancer development
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