Advertisement

Tumor Biology

, Volume 35, Issue 3, pp 2747–2751 | Cite as

AU-binding factor 1 expression was correlated with metadherin expression and progression of hepatocellular carcinoma

  • Yingzhuo Yang
  • Peng Kang
  • Jie Gao
  • Chunlin Xu
  • Shimei Wang
  • Haiyu Jin
  • Yunling Li
  • Wenjuan Liu
  • Xia Wu
Research Article

Abstract

RNA-binding factor 1 (AUF1) was found to be up-regulated in numerous tumors compared with untransformed tissues. Furthermore, it has been identified to regulate mRNAs en masse in hepatocellular carcinoma (HCC). Metadherin (MTDH) as a novel oncogene also promotes tumor progression and metastasis in HCC. Our study aimed to investigate the correlation between AUF1 and MTDH expressions by immunochemistry in 146 HCC patients from Heilongjiang region. AUF1 expression in HCC tumors was higher than that in the matched normal liver tissues. Particularly, AUF1 overexpression was closely associated with tumor size (P < 0.022), TNM stage (P < 0.003), hepatitis B surface antigen status, and AFP serum levels (P < 0.05). Furthermore, AUF1 overexpression led to poor outcome during 5-year follow-up (P < 0.001). Additionally, AUF1 and MTDH expressions were correlated with each other. Our findings suggest that the AUF1 gene may play an important role in HCC progression and be a novel biomarker in the future.

Keywords

Hepatocellular carcinoma RNA-binding factor 1 Metadherin (MTDH) Biomarker 

Notes

Acknowledgments

We thank the Foundation for Postdoctor of the Heilongjiang Provincial Government (no. LRB2010-355) and PHD of The Second Affiliated Hospital of Harbin Medical University (no. BS2011-23).

Conflicts of interest

None

References

  1. 1.
    Herceg Z, Paliwal A. Epigenetic mechanisms in hepatocellular carcinoma: how environmental factors influence the epigenome. Mutat Res Rev Mutat Res. 2011;727:55–61.CrossRefGoogle Scholar
  2. 2.
    Poon D, Anderson BO, Chen L-T, et al. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009;10:1111–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Corvalan AH. Early diagnosis of hepatocellular carcinoma by microRNAs: shining a light from the genome’s “dark matter”. Dig Dis Sci. 2012;57:1–3.Google Scholar
  4. 4.
    Zucconi BE, Wilson GM. Modulation of neoplastic gene regulatory pathways by the RNA-binding factor AUF1. Front Biosci J Virtual Libr. 2011;16:2307–14.CrossRefGoogle Scholar
  5. 5.
    DeMaria CT, Brewer G. AUF1 binding affinity to A + U-rich elements correlates with rapid mRNA degradation. J Biol Chem. 1996;271:12179–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Ing NH, Massuto DA, Jaeger LA. Estradiol up-regulates AUF1p45 binding to stabilizing regions within the 3′-untranslated region of estrogen receptor α mRNA. J Biol Chem. 2008;283:1764–72.PubMedCrossRefGoogle Scholar
  7. 7.
    Gratacos FM, Brewer G. The role of AUF1 in regulated mRNA decay. Wiley Interdiscip Rev RNA. 2010;1:457–73.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Wilson GM, Lu J, Sutphen K, et al. Regulation of A + U-rich element-directed mRNA turnover involving reversible phosphorylation of AUF1. J Biol Chem. 2003;278:33029–38.PubMedCrossRefGoogle Scholar
  9. 9.
    Vanzela E, Cardozo A. Is ARE/poly(U)-binding factor 1 (AUF1) a new player in cytokine-mediated beta cell apoptosis? Diabetologia. 2012;55:1572–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Sarkar S, Han J, Sinsimer KS, et al. RNA-binding protein AUF1 regulates lipopolysaccharide-induced IL10 expression by activating IkappaB kinase complex in monocytes. Mol Cell Biol. 2011;31:602–15.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Vázquez–Chantada M, Fernández–Ramos D, Embade N, et al. HuR/methyl-HuR and AUF1 regulate the MAT expressed during liver proliferation, differentiation, and carcinogenesis. Gastroenterology. 2010;138:1943–53.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Blaxall BC, Dwyer-Nield LD, Bauer AK, et al. Differential expression and localization of the mRNA binding proteins, AU-rich element mRNA binding protein (AUF1) and Hu antigen R (HuR), in neoplastic lung tissue. Mol Carcinog. 2000;28:76–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Xu N, Chen CY, Shyu AB. Versatile role for hnRNP D isoforms in the differential regulation of cytoplasmic mRNA turnover. Mol Cell Biol. 2001;21:6960–71.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Lapucci A, Donnini M, Papucci L, et al. AUF1 is a bcl-2 A + U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis. J Biol Chem. 2002;277:16139–46.PubMedCrossRefGoogle Scholar
  15. 15.
    Gautschi O, Ratschiller D, Gugger M, et al. Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung Cancer. 2007;55:1–14.PubMedCrossRefGoogle Scholar
  16. 16.
    Frau M, Tomasi ML, Simile MM, et al. Role of transcriptional and posttranscriptional regulation of methionine adenosyltransferases in liver cancer progression. Hepatology. 2012;56:165–75.PubMedCrossRefGoogle Scholar
  17. 17.
    Abdelmohsen K, Tominaga-Yamanaka K, Srikantan S, et al. RNA-binding protein AUF1 represses Dicer expression. Nucleic Acids Res. 2012;40:11531–44.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Raineri I, Wegmueller D, Gross B, et al. Roles of AUF1 isoforms, HuR and BRF1 in ARE-dependent mRNA turnover studied by RNA interference. Nucleic Acids Res. 2004;32:1279–88.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Fellows A, Griffina ME, Petrella BL, et al. AUF1/hnRNP D represses expression of VEGF in macrophages. Mol Biol Cell. 2011;18:772–91.Google Scholar
  20. 20.
    Su Z-Z, Kang D-C, Chen Y, et al. Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 2002;21:3592–602.PubMedCrossRefGoogle Scholar
  21. 21.
    Hu G, Chong RA, Yang Q, et al. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell. 2009;15:9–20.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Yoo BK, Emdad L. Su Z-z, et al. Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression. J Clin Invest. 2009;119:465–73.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    He X, Chang Y, Meng F, et al. MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. Oncogene. 2011;31:3357–69.PubMedCrossRefGoogle Scholar
  24. 24.
    Li C, Liu J, Lu R, et al. AEG-1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers. Int J Gynecol Cancer. 2011;21:602–15.PubMedCrossRefGoogle Scholar
  25. 25.
    Li C, Li Y, Wang X, et al. Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III–IV serous ovarian carcinoma. Histopathology. 2012;60:953–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Song H, Li C, Li R, et al. Prognostic significance of AEG-1 expression in colorectal carcinoma. Int J Color Dis. 2010;25:1201–9.CrossRefGoogle Scholar
  27. 27.
    Emdad L, Sarkar D. Su Z-z, et al. Activation of the nuclear factor κB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis. Cancer Res. 2006;66:1509–16.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhu K, Dai Z, Pan Q, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial–mesenchymal transition. Clin Cancer Res. 2011;17:7294–302.PubMedCrossRefGoogle Scholar
  29. 29.
    Zheng JS, Li C, Wu X, et al. Astrocyte elevated gene-1 is a novel biomarker of epithelial–mesenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumor Biol. 2013. doi: 10.1007/s13277-013-1300-3.Google Scholar
  30. 30.
    Ahn S, Hyeon J, Park C-K. Metadherin is a prognostic predictor of hepatocellular carcinoma after curative hepatectomy. Gut Liver. 2013;7:206–12.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Wu X, Wu S, Tong L, et al. miR-122 affects the viability and apoptosis of hepatocellular carcinoma cells. Scand J Gastroenterol. 2009;44:1332–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Yao N, Yao D, Wang L, et al. Inhibition of autocrine IGF-II on effect of human HepG2 cell proliferation and angiogenesis factor expression. Tumor Biol. 2012;33:1767–76.CrossRefGoogle Scholar
  33. 33.
    Lund N, Milev MP, Wong R, et al. Differential effects of hnRNP D/AUF1 isoforms on HIV-1 gene expression. Nucleic Acids Res. 2012;40:3663–75.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Yingzhuo Yang
    • 1
  • Peng Kang
    • 1
  • Jie Gao
    • 1
  • Chunlin Xu
    • 1
  • Shimei Wang
    • 1
  • Haiyu Jin
    • 1
  • Yunling Li
    • 1
  • Wenjuan Liu
    • 1
  • Xia Wu
    • 1
  1. 1.Department of Infectious DiseaseThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina

Personalised recommendations