Abstract

Xiaoxia Zhu^1,†,*,

Na Li¹,

Dianhe Li¹,

Zhou Sha¹,

Xiaokang Zheng^1,* and

Haofei Wang^2,*

²Department of Cardiothoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

^† These authors contributed equally to this work.

Abstract  Metastasis-associated gene 1 (MTA1) is associated with cell growth, metastasis, and survival in non-small-cell lung cancer (NSCLC). Several previous reports have demonstrated that microRNAs affect gene expression through interaction between their seed region and the 3′-untranslated region of the target mRNA, resulting in post-transcriptional regulation. The aim of this study was to identify miRNAs that suppress malignancy in NSCLC cells by targeting MTA1. Two human NSCLC cell lines were analyzed for the expression of MTA1 by quantitative RT-PCR and western blotting after transfection with MTA1 mimics. A luciferase reporter assay was established to test the direct connection between MTA1 and its upstream miRNAs. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine analysis, and colony formation assay. Cell migration and invasive capacity were evaluated by wound-healing assay and transwell assay. The miRNA/MTA1 axis was also probed by quantitative RT-PCR and western blotting in samples from eight NSCLC patients. Among the candidate miRNAs, miR-125a-3p was shown to post-transcriptionally regulate MTA1 in NSCLC cells. These data were reinforced by the luciferase reporter assay, in addition to the demonstration that MTA1 is inversely correlated with miR-125a-3p in NSCLC tissues. Furthermore, miR-125a-3p was found to inhibit NSCLC cell proliferation, migration, and invasion, through the same mechanisms of down-regulated MTA1. Our report demonstrates that miR-125a-3p inhibits the proliferation, migration, and invasion of NSCLC cells through down-regulation of MTA1, indicating the role of the miR-125a-3p/MTA1 axis in NSCLC, and may provide novel insight into the molecular mechanisms underpinning the disease and potential therapeutic targets.

Keywords   miR-125a-3p; metastasis-associated gene 1 (MTA1); non-small-cell lung cancer; proliferation; invasion

Received   2015-1-18　　

Accepted  2015-3-13

Funding  This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81001047 and 81071827), the Science and technology projects in Guangdong Province (No. 2012B031800127), the Excellent Young Teachers Program of Higher Educat

* Correspondence address  Tel: +86-20-62787484; Fax: +86-20-61641034; E-mail: [email protected] (X.X.Z.)/[email protected] (X.K.Z.)/[email protected] (H.F.W.)