MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1

BMC Cancer

Research Article

Ming Sun¹  Wei De¹  Zhao-Xia Wang²  Jing Liu²  Zhi-Li Liu²  Kai-Hua Lu³ 

[1] Department of Biochemistry and Molecular Biology, Nanjing Medical University, 210029, Nanjing, Jiangsu, People's Republic of China;Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, 210011, Nanjing, Jiangsu, People's Republic of China;Immunology and Reproductive Biology Lab of Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210093, Nanjing, Jiangsu, People's Republic of China;Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, People's Republic of China;

关键词: A549 Cell;    NSCLC Patient;    NSCLC Cell;    NSCLC Tissue;    Nontumor Tissue;   

DOI  :  10.1186/1471-2407-12-519

 received in 2012-07-04, accepted in 2012-11-12,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPolo-like kinase 1 (PLK1) is highly expressed in many human cancers and regulates critical steps in mitotic progression. Previously, we have reported that PLK1 was overexpressed in non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms are not well understood. By using microRNA (miR) target prediction algorithms, we identified miR-100 that might potentially bind the 3’-untranslated region of PLK1 transcripts. The purpose of this study was to investigate the roles of miR-100 and its association with PLK1 in NSCLC development.MethodsTaqman real-time quantitative RT-PCR assay was performed to detect miR-100 expression 10 NSCLC tissues and corresponding nontumor tissues. Additionally, the expression of miR-100 in 110 NSCLC tissues and its correlation with clinicopathological factors or prognosis of patients was analyzed. Finally, the effects of miR-100 expression on growth, apoptosis and cell cycle of NSCLC cells by posttranscriptionally regulating PLK1 expression were determined.ResultsMiR-100 was significantly downregulated in NSCLC tissues, and low miR-100 expression was found to be closely correlated with higher clinical stage, advanced tumor classification and lymph node metastasis of patients. The overall survival of NSCLC patients with low miR-100 was significantly lower than that of those patients with high miR-100, and univariate and multivariate analyses indicated that low miR-100 expression might be a poor prognostic factor. Also, miR-100 mimics could lead to growth inhibition, G2/M cell cycle arrest and apoptosis enhancement in NSCLC cells. Meanwhile, miR-100 mimics could significantly inhibit PLK1 mRNA and protein expression and reduce the luciferase activity of a PLK1 3’ untranslated region-based reporter construct in A549 cells. Furthermore, small interfering RNA (siRNA)-mediated PLK1 downregulation could mimic the effects of miR-100 mimics while PLK1 overexpression could partially rescue the phenotypical changes of NSCLC cells induced by miR-100 mimics.ConclusionsOur findings indicate that low miR-100 may be a poor prognostic factor for NSCLC patients and functions as a tumor suppressor by posttranscriptionally regulating PLK1 expression.

【 授权许可】

Unknown   
© Liu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.