Abstract
BackgroundIt is well known that nuclear factor of activated T cells c1 (NFATc1) expression is closely associated with progression of many cancers. And we found that miR‐338 could directly target the NFATc1. However, the precise mechanisms of miR‐338 in non‐small‐cell lung cancer (NSCLC) have not been well clarified. Our study aimed to explore the interaction between NFATc1 and miR‐338 in NSCLC.MethodsQuantitative RT‐PCR was utilized to determine the expressions of NFATc1 and miR‐338 in NSCLC tissues and cell lines. And the cell proliferation and epithelial‐mesenchymal transition (EMT) were assessed to determine the functional roles of miR‐338 and NFATc1 in NSCLC cells. NFATc1 expression was detected using quantitative RT‐PCR and western blotting, respectively. Luciferase reporter assays were performed to validate NFATc1 as a target of miR‐338 in NSCLC cells.ResultsIn this study, our results showed that NFATc1 expression was significantly up‐regulated in NSCLC tissues and cell lines, and the miR‐338 level was dramatically down‐regulated. Moreover high NFATc1 expression was closely associated with low miR‐338 level in NSCLC tissues. Moreover introduction of miR‐338 significantly inhibited proliferation and EMT of NSCLC cells. Bioinformatics analysis predicted that the NFATc1 was a potential target gene of miR‐338. We demonstrated that miR‐338 could directly target NFATc1 by using luciferase reporter assay. Besides, knockdown of NFATc1 had the similar effects with miR‐338 overexpression on NSCLC cells. Up‐regulation of NFATc1 in NSCLC cells partially abolished the inhibitory effects of miR‐338 mimic.ConclusionsOverexpression of miR‐338 inhibited cell proliferation and EMT of NSCLC cells by directly down‐regulating NFATc1 expression.
Highlights
Lung cancer, one of the most frequently diagnosed cancers, leads to the largest number of cancer-related deaths worldwide (Zhang, Shao, Lin, Liu, & Yang, 2017; Zhang, Ding, & Zhang, 2017)
Our findings indicated that the mRNA level of nuclear factor of activated T cells c1 (NFATc1) was the highest in non-small-cell lung cancer (NSCLC) tissues among these four Nuclear factor of activated T-cells (NFAT) genes compared with the adjacent tissues (Figure 1a)
EMT, epithelial-mesenchymal transition; NSCLC, non-small-cell lung cancer increased NFATc1 expression could reverse the inhibitory effect of the miR-338 overexpression on EMT markers of NSCLC cells (Figure 5d), decrease the expression of E-cadherin enhanced by miR-338 mimic, and increase the expressions of N-cadherin and Vimentin reduced by miR-338 mimic
Summary
One of the most frequently diagnosed cancers, leads to the largest number of cancer-related deaths worldwide (Zhang, Shao, Lin, Liu, & Yang, 2017; Zhang, Ding, & Zhang, 2017). More and more reports suggested that NFAT signaling plays a critical role in tumor growth and tumorigenesis (Jauliac et al, 2002). Isoform-specific functions of NFAT in different types of neoplasms have been indicated in immune cells Among these five isoforms, high expression of NFATc1 has often been determined in many types of cancers such as hepatic, pulmonary and pancreatic carcinomas, compared with their corresponding benign tissues (Buchholz et al, 2006; Chen et al, 2011; Wang et al, 2012). Our outcomes showed critical roles for miR-338/ NFATc1 axis in the pathogenesis of NSCLC and suggested its possible application in tumor treatment
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