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MiR-3910 Promotes the Growth and Migration of Cancer Cells in the Progression of Hepatocellular Carcinoma

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Abstract

Introduction

Previous studies have reported that specific depletion of mammalian sterile-like kinase (MST1) in the mouse liver driven Hepatocellular carcinoma (HCC). However, how the expression of MST1 was regulated in the progression of HCC remains largely unknown.

Materials and methods

The expression of miR-3910 in the HCC tissues and cell lines were examined using q-PCR. The functions of miR-3910 in HCC were examined using MTT assay, Boyden chamber assay and soft agar assay. The effects of miR-3910 on the metastasis of HCC cells were evaluated using the mouse model.

Results

Here, we have shown that miR-3910 regulated the expression of MST1. MiR-3910 was up-regulated in HCC samples and cell lines, and the expression of miR-3910 was induced by the oncogenic RasV12. In the functional study, miR-3910 was found to promote the growth and migration of HCC cells, and knocking down miR-3910 inhibited the metastasis of HCC cells. Mechanically, it was found that miR-3910 activated YAP signaling by targeting MST1.

Conclusion

Taken together, this study demonstrated that miR-3910 exerted oncogenic effects on the progression of HCC and suggested that miR-3910 might be a therapeutic target for cancer therapy.

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References

  1. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66:271–289.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  PubMed  Google Scholar 

  3. Wei W, Chua MS, Grepper S, So S. Small molecule antagonists of Tcf4/beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo. Int J Cancer. 2010;126:2426–2436.

    CAS  PubMed  Google Scholar 

  4. Calvisi DF, Ladu S, Gorden A, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology. 2006;130:1117–1128.

    Article  CAS  PubMed  Google Scholar 

  5. Fitamant J, Kottakis F, Benhamouche S, et al. YAP inhibition restores hepatocyte differentiation in advanced HCC, leading to tumor regression. Cell Rep. 2015;10:1692–1707.

    Article  CAS  Google Scholar 

  6. Codelia VA, Irvine KD. Hippo signaling goes long range. Cell. 2012;150:669–670.

    Article  CAS  PubMed  Google Scholar 

  7. Badouel C, McNeill H. SnapShot: the hippo signaling pathway. Cell. 2011;145(3):484–484, e481.

  8. Harvey KF, Pfleger CM, Hariharan IK. The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell. 2003;114:457–467.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao B, Lei Q, Guan KL. Mst out and HCC in. Cancer Cell. 2009;16:363–364.

    Article  CAS  PubMed  Google Scholar 

  10. Chen X, Chen Y, Dong J. MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity. Cell Signal. 2016;28:1826–1832.

    Article  CAS  PubMed  Google Scholar 

  11. Rawat SJ, Araiza-Olivera D, Arias-Romero LE, et al. H-ras inhibits the hippo pathway by promoting Mst1/Mst2 heterodimerization. Curr Biol. 2016;26:1556–1563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Elemeery MN, Badr AN, Mohamed MA, Ghareeb DA. Validation of a serum microRNA panel as biomarkers for early diagnosis of hepatocellular carcinoma post-hepatitis C infection in Egyptian patients. World J Gastroenterol. 2017;23:3864–3875.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fu X, Wen H, Jing L, et al. MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3 K/Akt pathway. Cancer Sci. 2017;108:620–631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen SY, Ma DN, Chen QD, et al. MicroRNA-200a inhibits cell growth and metastasis by targeting Foxa2 in hepatocellular carcinoma. J Cancer. 2017;8:617–625.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ge H, Zou D, Wang Y, Jiang H, Wang L. MicroRNA-377 downregulates Bcl-xL and increases apoptosis in hepatocellular carcinoma cells. Oncol Res. 2017;25:29–34.

    Article  PubMed  Google Scholar 

  16. Mobus S, Yang D, Yuan Q, et al. MicroRNA-199a-5p inhibition enhances the liver repopulation ability of human embryonic stem cell-derived hepatic cells. J Hepatol. 2015;62:101–110.

    Article  PubMed  Google Scholar 

  17. Li S, Ran Y, Zhang D, Chen J, Li S, Zhu D. MicroRNA-138 plays a role in hypoxic pulmonary vascular remodelling by targeting Mst1. Biochem J. 2013;452:281–291.

    Article  CAS  PubMed  Google Scholar 

  18. Valero V 3rd, Pawlik TM, Anders RA. Emerging role of Hpo signaling and YAP in hepatocellular carcinoma. J Hepatocell Carcinoma. 2015;2:69–78.

    PubMed  PubMed Central  Google Scholar 

  19. He S, Zhang J, Lin J, Zhang C, Sun S. Expression and function of microRNA-27b in hepatocellular carcinoma. Mol Med Rep. 2016;13:2801–2808.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang L, Xiang ZL, Zeng ZC, Fan J, Tang ZY, Zhao XM. A microRNA-based prediction model for lymph node metastasis in hepatocellular carcinoma. Oncotarget. 2016;7:3587–3598.

    Article  PubMed  Google Scholar 

  21. Tamori A, Murakami Y, Kubo S, et al. MicroRNA expression in hepatocellular carcinoma after the eradication of chronic hepatitis virus C infection using interferon therapy. Hepatol Res. 2016;46:E26–E35.

    Article  CAS  PubMed  Google Scholar 

  22. Childs-Disney JL, Disney MD. Small molecule targeting of a microRNA associated with hepatocellular carcinoma. ACS Chem Biol. 2016;11:375–380.

    Article  CAS  PubMed  Google Scholar 

  23. Perra A, Kowalik MA, Ghiso E, et al. YAP activation is an early event and a potential therapeutic target in liver cancer development. J Hepatol. 2014;61:1088–1096.

    Article  CAS  PubMed  Google Scholar 

  24. Bera R, Chiou CY, Yu MC, et al. Functional genomics identified a novel protein tyrosine phosphatase receptor type F-mediated growth inhibition in hepatocarcinogenesis. Hepatology. 2014;59:2238–2250.

    Article  CAS  PubMed  Google Scholar 

  25. Murakami Y, Toyoda H, Tanaka M, et al. The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families. PloS ONE. 2011;6:e16081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Amr KS, Ezzat WM, Elhosary YA, Hegazy AE, Fahim HH, Kamel RR. The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma. Gene. 2016;575:66–70.

    Article  CAS  PubMed  Google Scholar 

  27. Zhan Y, Zheng N, Teng F, Bao L, Liu F, Zhang M, Guo M, Guo W, Ding G, Wang Q: MiR-199a/b-5p inhibits hepatocellular carcinoma progression by post-transcriptionally suppressing ROCK1. Oncotarget 2017.

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Correspondence to Shuangyin Han.

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Ethical approval research involving animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Cheng, L., Wang, H. & Han, S. MiR-3910 Promotes the Growth and Migration of Cancer Cells in the Progression of Hepatocellular Carcinoma. Dig Dis Sci 62, 2812–2820 (2017). https://doi.org/10.1007/s10620-017-4670-3

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  • DOI: https://doi.org/10.1007/s10620-017-4670-3

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