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MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN

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Abstract

MicroRNAs (miRNAs) regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. In our previous study, we have shown that expression of serum microRNA (miR)-21 is correlated with TNM stage and lymph node metastasis and might be an independent prognostic factor for NSCLC patients. However, the roles of miR-21 overexpression in NSCLC development are still unclear. The purpose of this study is to investigate the effect of miR-21 and determine whether miR-21 can be a therapeutic target for human NSCLC. Taqman real-time quantitative RT-PCR assay was performed to detect miR-21 expression in NSCLC cell lines and tissues. Next, the effects of miR-21 expression on NSCLC cell characteristics including growth, invasion, and chemo- or radioresistance were also determined. Results showed that miR-21 is commonly upregulated in NSCLC cell lines and tissues with important functional consequences. In addition, we found that anti-miR-21 could significantly inhibit growth, migration and invasion, and reverse chemo- or radioresistance of NSCLC cells, while miR-21 mimics could increase growth, promote migration and invasion, and enhance chemo- or radioresistance of NSCLC cells. Meanwhile, miR-21 mimics could inhibit expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3′-untranslated region (UTR)-based reporter construct in A549 cells, while anti-miR-21 could increase expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3′-UTR-based reporter construct in A549 cells. Furthermore, overexpression of PTEN could mimic the same effects of anti-miR-21 in NSCLC cells, and siRNA-mediated downregulation of PTEN could rescue the effects on NSCLC cells induced by anti-miR-21. Taken together, these results provide evidence to show the promotion role of miR-21 in NSCLC development through modulation of the PTEN signaling pathway.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 30973477), the Natural Science Foundation of Jiangsu province (No. BK2010590), the Medical Key Talented Person Foundation of the Jiangsu Provincial Developing Health Project (RC2011080), the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project (No. 09-B1-021), and Foundation of the Second Affiliated Hospital of Nanjing Medical University to Bring New Ideas Team.

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Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan Road, Nanjing, 210011, Jiangsu, People’s Republic of China

    Zhi-Li Liu, He Wang, Jing Liu & Zhao-Xia Wang

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  1. Zhi-Li Liu
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  2. He Wang
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  3. Jing Liu
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  4. Zhao-Xia Wang
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Correspondence to Zhao-Xia Wang.

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Zhi-Li Liu and He Wang should be regarded as joint first authors for their equal contributions.

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Liu, ZL., Wang, H., Liu, J. et al. MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN. Mol Cell Biochem 372, 35–45 (2013). https://doi.org/10.1007/s11010-012-1443-3

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  • DOI: https://doi.org/10.1007/s11010-012-1443-3

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