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miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3

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Abstract

The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to the development of invasion and metastasis. Recent data strongly suggests the important role of miRNAs in cancer progression, including invasion and metastasis. Here, we found miR-217 expression was much lower in highly invasive MHCC-97H HCC cells and metastatic HCC tissues. Restored miR-217 expression with miR-217 mimics inhibited invasion of MHCC-97H cells. Inversely, miR-217 inhibition enhanced the invasive ability of Huh7 and MHCC-97L cells. Mechanically, bioinformatics analysis combined with experimental analysis demonstrated E2F3 was a novel direct target of miR-217. Moreover, E2F3 protein level was positively associated with HCC metastasis and functional analysis confirmed the positive role of E2F3 in HCC cell invasion. Our findings suggest miR-217 function as a potential tumor suppressor in HCC progression and miR-217-E2F3 axis may be a novel candidate for developing rational therapeutic strategies.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  2. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576

    Article  CAS  PubMed  Google Scholar 

  3. Thomas MB, Jaffe D, Choti MM et al (2010) Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 28:3994–4005

    Article  PubMed Central  PubMed  Google Scholar 

  4. White NMA, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM (2010) Metastamirs: a stepping stone towards improved cancer management. Nat Rev Clin Oncol 8:75–84

    Article  PubMed  Google Scholar 

  5. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  7. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  8. Ventura A, Jacks T (2009) MicroRNAs and cancer: short RNAs go a long way. Cell 136:586–591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Iorio MV, Croce CM (2009) MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol 27:5848–5856

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Valastyan S, Reinhardt F, Benaich N et al (2009) A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 137:1032–1046

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Yao J, Liang L, Huang S et al (2010) MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in hepatocellular carcinoma. Hepatology 51:846–856

    CAS  PubMed  Google Scholar 

  12. Yang F, Yin Y, Wang F et al (2010) miR-17-5p Promotes migration of human hepatocellular carcinoma cells through the p38 mitogen-activated protein kinase-heat shock protein 27 pathway. Hepatology 51:1614–1623

    Article  CAS  PubMed  Google Scholar 

  13. Bai S, Nasser MW, Wang B et al (2009) MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 284:32015–32027

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Tsai WC, Hsu PW, Lai TC et al (2009) MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 49:1571–1582

    Article  CAS  PubMed  Google Scholar 

  15. Zhao WG, Yu SN, Lu ZH et al (2010) The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis 31:1726–1733

    Article  CAS  PubMed  Google Scholar 

  16. Bracken AP, Ciro M, Cocito A, Helin K (2004) E2F target genes: unraveling the biology. Trends Biochem Sci 29:409–417

    Article  CAS  PubMed  Google Scholar 

  17. McClellan KA, Slack RS (2007) Specific in vivo roles for E2Fs in differentiation and development. Cell Cycle 6:2917–2927

    Article  CAS  PubMed  Google Scholar 

  18. Leone G, DeGregori J, Yan Z et al (1998) E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Gene Dev 12:2120–2130

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Humbert PO, Verona R, Trimarchi JM et al (2000) E2F3 is critical for normal cellular proliferation. Genes Develop 14:690–703

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Orlic M, Spencer CE, Wang L, Gallie BL (2006) Expression analysis of 6p22 genomic gain in retinoblastoma. Genes Chromosomes Cancer 45:72–82

    Article  CAS  PubMed  Google Scholar 

  21. Andre F, Job B, Dessen P et al (2009) Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array. Clin Cancer Res 15:441–451

    Article  CAS  PubMed  Google Scholar 

  22. Feber A, Clark J, Goodwin G et al (2004) Amplification and overexpression of E2F3 in human bladder cancer. Oncogene 23:1627–1630

    Article  CAS  PubMed  Google Scholar 

  23. Oeggerli M, Tomovska S, Schraml P et al (2004) E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. Oncogene 23:5616–5623

    Article  CAS  PubMed  Google Scholar 

  24. Foster CS, Falconer A, Dodson AR et al (2004) Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Oncogene 23:5871–5879

    Article  CAS  PubMed  Google Scholar 

  25. Borczuk A, Gorenstein L, Walter KL et al (2003) Non-small-cell lung cancer molecular signatures recapitulate lung developmental pathways. Am J Pathol 163:1949–1960

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Lu KH, Patterson AP, Wang L et al (2004) Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res 10:3291–3300

    Article  CAS  PubMed  Google Scholar 

  27. Paulson QX, McArthur MJ, Johnson DG (2006) E2F3a stimulates proliferation, p53-independent apoptosis and carcinogenesis in a transgenic mouse model. Cell Cycle 5:184–190

    Article  CAS  PubMed  Google Scholar 

  28. Noguchi S, Mori T, Otsuka Y et al (2012) Anti-oncogenic MicroRNA-203 induces senescence by targeting E2F3 protein in human melanoma cells. J Biol Chem 287:11769–11777

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Tazawa H, Tsuchiya N, Izumiya M, Nakagama H (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA 104:15472–15477

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Ren XS, Yin MH, Zhang X et al (2013) Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells. Cancer Lett. doi:10.1016/j.canlet.2013.10.031

    Google Scholar 

  31. Feng B, Wang R, Song HZ, Chen LB (2012) MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3. Cancer 118:3365–3376

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Meizuo Zhong.

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Su, J., Wang, Q., Liu, Y. et al. miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3. Mol Cell Biochem 392, 289–296 (2014). https://doi.org/10.1007/s11010-014-2039-x

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  • DOI: https://doi.org/10.1007/s11010-014-2039-x

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