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Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc

Gene Therapy volume 22, pages 729–738 (2015)Cite this article

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Abstract

Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous cancers and involved in tumorigenesis, whereas their influences on pancreatic cancer (PC) still need further elucidation. The present research revealed that miR-494 was significantly decreased in PC cell lines and tissues. Functional study showed that overexpressed miR-494 could remarkably inhibit proliferation of PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1-phase arrest and senescence. Moreover, upregulated miR-494 significantly prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified as targets of miR-494 through dual luciferase assay and further confirmed by the reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore, co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and SIRT1 expression, and inhibited proliferation of PC, which simulated the effects of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1 effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical characteristics further revealed that low miR-494 correlated with larger tumor size, late tumor node metastasis stage, lymphatic invasion, distant metastasis and poor prognosis. In conclusion, the present study indicated that miR-494 might serve as predictor and inhibitor in PC by directy downregulating the loop of c-Myc and SIRT1.

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Acknowledgements

This study was supported from the National Science Foundation Committee (NSFC) of China (Grant number: 30972900 and 81372666) and the Research Special Fund for Public Welfare Industry of Health of China (Grant number: 201202007).

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Author notes

  1. Y Liu and X Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Pancreatic Disease Institute, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, China

    Y Liu, X Li, S Zhu, M Yang, Q Qin, S-c Deng, K Tian, L Liu, Y Niu, C-y Wang & G Zhao

  2. Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, China

    J-g Zhang

  3. Department of Gastroenterological Surgery, Peking University People's Hospital, Xicheng District, Beijing, China

    B Wang

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  1. Y Liu
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Correspondence to C-y Wang or G Zhao.

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Liu, Y., Li, X., Zhu, S. et al. Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc. Gene Ther 22, 729–738 (2015). https://doi.org/10.1038/gt.2015.39

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