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miR-21 modulates chemosensitivity of tongue squamous cell carcinoma cells to cisplatin by targeting PDCD4

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Abstract

Chemoresistance is a challenge for clinician in management of tongue cancer. Therefore, it is necessary to explore alternative therapeutic methods to overcome drug resistance. miRNAs are endogenous −22nt RNAs that play important regulatory roles by targeting mRNAs. miR-21, an essential oncogenic molecule, is associated with chemosensitivity of several human cancer cells to anticancer agents. In this study, we investigated the effects and molecular mechanisms of miR-21 in chemosensitivity of tongue squamous cell carcinoma cells (TSCC) to cisplatin. miR-21 expression was detected in tongue cancer tissue using RT-PCR and PDCD4 protein expression was measured using immunohistochemistry. miR-21 and(or) PDCD4 depleted cell lines were generated using miR-21 inhibitor and(or) siRNA. The viabilities of treated cells were analyzed using MTT assay. RT-PCR was used to detect miR-21 expression and immunoblotting was used to detect protein levels. Cell cycle and apoptosis were analyzed using propidium iodide (PI) staining and Annexin V/PI staining, respectively. The expression of miR-21 in tumorous tissue was significantly higher compared with adjacent normal tissue and loss of PDCD4 expression was observed in TSCCs. Transfection of miR-21 inhibitor induced sensitivity of TSCC cells (Tca8113 and CAL-27) to cisplatin. TSCC cells transfected with PDCD4 siRNA became more resistant to cisplatin therapy. We found an increase PDCD4 protein level following the transfection of miR-21 inhibitor using Western blot analysis. In addition, the enhanced growth-inhibitory effect by miR-21 inhibitor was weakened after the addition of PDCD4 siRNA. Suppression of miR-21 or PDCD4 could significantly promote or reduce cisplatin-induced apoptosis, respectively. Our data suggest that miR-21 could modulate chemosensitivity of TSCC cells to cisplatin by targeting PDCD4, and miR-21 may serve as a potential target for TSCC therapy.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (81272957), Specialized Research Fund for the Doctoral Program of Higher Education (20120201110063, 20130201120054), the Fundamental Research Funds for the Central Universities (XJJ2013057) and innovation project of Shaanxi province (2012KTCL03-17).

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We declare that we have no conflict of interest

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery/Head and Neck Surgery, Stomatological Hospital, College of Stomatology, Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, China

    Wenhao Ren, Xiaolong Wang, Ling Gao, Shaoming Li, Xiaojing Yan, Jin Zhang, Yincheng Zhang & Keqian Zhi

  2. Department of Genetics and Molecular Biology, College of Medicine, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, China

    Ling Gao & Chen Huang

  3. Department of Oral and Maxillofacial Surgery, Stomatological Hospital, College of Stomatology, Xi’an Jiaotong University, Number 98, Xiwu Road, Xi’an, 710004, Shaanxi, China

    Keqian Zhi

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  1. Wenhao Ren
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  2. Xiaolong Wang
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  3. Ling Gao
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Correspondence to Keqian Zhi.

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Xiaolong Wang, Ling Gao, and Wenhao Ren are co-first authors and contributed equally to this article.

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Ren, W., Wang, X., Gao, L. et al. miR-21 modulates chemosensitivity of tongue squamous cell carcinoma cells to cisplatin by targeting PDCD4. Mol Cell Biochem 390, 253–262 (2014). https://doi.org/10.1007/s11010-014-1976-8

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