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miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3

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Tumor Biology

Abstract

microRNAs play an important role in the progression of hepatocellular carcinoma (HCC). In this study, we found that miR-582-5p expression was downregulated in hepatoma tissues and HCC cell lines. Upregulation of miR-582-5p reduced colony number, inhibited cellular proliferation, and arrested cell cycle in G0/G1 phase. When miR-582-5p was inhibited, the colony number was increased and cellular proliferation and cell cycle were promoted. Further studies showed that miR-582-5p regulated the progression of HCC through directly inhibiting the expression of CDK1 and AKT3, and indirectly inhibiting the expression of cyclinD1.

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Acknowledgments

The study was supported by The Natural Science Foundation of China, No: 30371394; Natural Science Fund of Hubei Province, No: 2012FFA044; the Health Department Found of Hubei Province, No: JX6B18; Public Service Platform Construction Projects of Wuhan Technology Bureau, No: 2013060705010326.

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    Authors and Affiliations

    1. Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China

      Yi Zhang, Yan Xiong, Zibiao Zhong, Xiaoli Fan, Zhenghua Wang & Qifa Ye

    2. Oncology Department of the First People’s Hospital of Shunde, Guangzhou, China

      Wei Huang

    3. Anesthesia Department, Zhongnan Hospital of Wuhan University, Wuhan, China

      Yan Ran

    4. Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, China

      Qifa Ye

    5. Zhongnan Hospital of Wuhan University, Donghu Road 169#, Wuchang District, Wuhan, 430071, China

      Qifa Ye

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    1. Yi Zhang
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    Corresponding author

    Correspondence to Qifa Ye.

    Additional information

    Yi Zhang and Wei Huang contributed equally to this work.

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    Supplementary Figure 1

    miR-582-5p is downregulation in human HCC tissues. N represents non-tumor liver tissues, T represents HCC tissues. (DOC 67 kb)

    Supplementary Figure 2

    miR-582-5p targets CDK1 and AKT3 by binding to its 3′ UTR. Indicated HCC cells Huh-7 and Hep3B were contransfected with miR-582-5p mimic or miR-582-5p inhibitor and luciferase reporters containing the mutational miRNA target site in the 3′ UTR of CDK1 or AKT3. *p < 0.05, Error bars represent mean ± STDEV. (DOC 338 kb)

    Supplementary Figure 3

    miR-582-5p regulates E2F1 expression. (A) Western blot assay finds that overexpression of miR-582-5p inhibits E2F1 expression, knockdown of miR-582-5p promotes F2F1 expression in indicated cell lines. (B) Real-time PCR assay finds that overexpression of miR-582-5p inhibits E2F1 expression, knockdown of miR-582-5p promotes F2F1 expression in indicated cell lines. *p < 0.05, Error bars represent mean ± STDEV. (DOC 130 kb)

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    Zhang, Y., Huang, W., Ran, Y. et al. miR-582-5p inhibits proliferation of hepatocellular carcinoma by targeting CDK1 and AKT3. Tumor Biol. 36, 8309–8316 (2015). https://doi.org/10.1007/s13277-015-3582-0

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    • DOI: https://doi.org/10.1007/s13277-015-3582-0

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