Tumor Biology

, Volume 36, Issue 11, pp 9049–9057 | Cite as

MiR-570 inhibited the cell proliferation and invasion through directly targeting B7-H1 in hepatocellular carcinoma

  • Wei Guo
  • Wei Tan
  • Shan Liu
  • Xuhui Huang
  • Juze Lin
  • Ronghua Liang
  • Le Su
  • Qiao Su
  • Changjun WangEmail author
Research Article


A recent study reported that miR-570 was the most important microRNA in the microRNA gene networks of alcoholic liver disease that has the potential of progressing to hepatocellular carcinoma. However, litter is known regarding the expression and specific function of miR-570 in the progression of hepatocellular carcinoma, especially its molecular mechanisms by which miR-570 exerts its functions and modulates the malignant phenotypes of hepatocellular carcinoma cells. Here, we observed that miR-570 was highly expressed in hepatocellular carcinoma cell lines (Bel-7404, Huh-7, and HepG2), while B7-H1 was lowly expressed, compared to nonmalignant cell line (L-02 and HL-7702). Transfection of miR-570 mimics or knockdown of B-H1 suppressed the expression of B7-H1, which promotes cell apoptosis and inhibits the cell proliferation and invasion. Using a dual-luciferase reporter system, we verified that B7-H1 is a direct target of miR-570. The overexpression of B7-H1 reversed the inhibition of proliferation and invasion by miR-570. In addition, miR-570 suppressed tumorigenicity in vivo. Hence, our observation confirmed that miR-570 works as proliferation and metastatic suppressor in hepatocellular carcinoma cells through directly targeting B7-H1 in hepatocellular carcinoma cell and rationally presents that miR-570 has the potential to be a useful clinical noninvasive diagnostics or predictive marker in human hepatocellular carcinoma.


miR-570 B7-H1 Hepatocellular carcinoma cell Tumorigenicity 



This research was supported by the National Natural Science Foundation of China (81373582, 81302958), the Natural Science Foundation of Guangdong Province, China (S2013010012636), and the Administration of Traditional Chinese Medicine of Guangdong, China (20141003, 20141001). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflicts of interest



  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lu T, Seto WK, Zhu RX, Lai CL, Yuen MF. Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection. World J Gastroenterol WJG. 2013;19:8887–94.CrossRefPubMedGoogle Scholar
  4. 4.
    Zhu Z, Zhang X, Wang G, Zheng H. Role of micrornas in hepatocellular carcinoma. Hepat Mon. 2014;14:e18672.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microrna targets. Cell. 2005;120:15–20.CrossRefPubMedGoogle Scholar
  6. 6.
    Lai EC. MicroRNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet. 2002;30:363–4.CrossRefPubMedGoogle Scholar
  7. 7.
    Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10:704–14.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chan B, Manley J, Lee J, Singh SR. The emerging roles of microRNAs in cancer metabolism. Cancer Lett. 2015;356:301–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Gailhouste L, Ochiya T. Cancer-related microRNAs and their role as tumor suppressors and oncogenes in hepatocellular carcinoma. Histol Histopathol. 2013;28:437–51.PubMedGoogle Scholar
  10. 10.
    Callegari E, Elamin BK, Sabbioni S, Gramantieri L, Negrini M. Role of microRNAs in hepatocellular carcinoma: a clinical perspective. Onco Targets ther. 2013;6:1167–78.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Catto JW, Alcaraz A, Bjartell AS, De Vere WR, Evans CP, Fussel S, et al. Microrna in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 2011;59:671–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Li W, Xie L, He X, Li J, Tu K, Wei L, et al. Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma. Int J Cancer J Int Cancer. 2008;123:1616–22.CrossRefGoogle Scholar
  13. 13.
    Liu Y, Chen SH, Jin X, Li YM. Analysis of differentially expressed genes and microRNAs in alcoholic liver disease. Int J Mol Med. 2013;31:547–54.PubMedGoogle Scholar
  14. 14.
    Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800.CrossRefPubMedGoogle Scholar
  15. 15.
    Wang W, Sun J, Li F, Li R, Gu Y, Liu C, et al. A frequent somatic mutation in CD274 3′-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding. Hum Mutat. 2012;33:480–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007;13:84–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Gong AY, Zhou R, Hu G, Li X, Splinter PL, O’Hara SP, et al. MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol. 2009;182:1325–33.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Conner SD, Schmid SL. Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. J Cell Biol. 2002;156:921–9.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Yoon HG, Chan DW, Huang ZQ, Li J, Fondell JD, Qin J, et al. Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1. EMBO J. 2003;22:1336–46.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zhang XM, Chang Q, Zeng L, Gu J, Brown S, Basch RS. TBLR1 regulates the expression of nuclear hormone receptor co-repressors. BMC Cell Biol. 2006;7:31.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Xiao-feng LI, Cai-xia BA, Hai-qing YUAN, Mei-yun ZHANG, Xue-feng BAI GAOH. The expressions of B7-H1 and BCL-2 in human colorectal cancer and their clinical significance. Tumor. 2012;32:555–8.Google Scholar
  22. 22.
    Vaillant F, Merino D, Lee L, Breslin K, Pal B, Ritchie ME, et al. Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell. 2013;24:120–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Xin M, Li R, Xie M, Park D, Owonikoko TK, Sica GL, et al. Small-molecule Bax agonists for cancer therapy. Nat Commun. 2014;5:4935.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    You S, Li R, Park D, Xie M, Sica GL, Cao Y, et al. Disruption of STAT3 by niclosamide reverses radioresistance of human lung cancer. Mol Cancer Ther. 2014;13:606–16.CrossRefPubMedGoogle Scholar
  25. 25.
    Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N. Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 2006;108:19–24.CrossRefPubMedGoogle Scholar
  26. 26.
    Xia Y, Chen R, Ye SL, Sun R, Chen J, Zhao Y. Inhibition of T-cell responses by intratumoral hepatic stellate cells contribute to migration and invasion of hepatocellular carcinoma. Clin Exp Metastasis. 2011;28:661–74.CrossRefPubMedGoogle Scholar
  27. 27.
    Shi SJ, Wang LJ, Wang GD, Guo ZY, Wei M, Meng YL, et al. B7-H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells. PLoS One. 2013;8:e76012.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Wang H, Chen L. Tumor microenviroment and hepatocellular carcinoma metastasis. J Gastroenterol Hepatol. 2013;28 Suppl 1:43–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Zhu J, Chen L, Zou L, Yang P, Wu R, Mao Y, et al. miR-20b, −21, and -130b inhibit PTEN expression resulting in B7-H1 over-expression in advanced colorectal cancer. Hum Immunol. 2014;75:348–53.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Wei Guo
    • 1
  • Wei Tan
    • 1
  • Shan Liu
    • 2
  • Xuhui Huang
    • 1
  • Juze Lin
    • 1
  • Ronghua Liang
    • 1
  • Le Su
    • 1
  • Qiao Su
    • 3
  • Changjun Wang
    • 1
    Email author
  1. 1.Department of Traditional Chinese Medicine, Guangdong Geriatric Institute, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouChina
  2. 2.Tropical Medicine InstituteGuangzhou University of Chinese MedicineGuangzhouChina
  3. 3.Laboratory Animal CenterThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina

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