Tumor Biology

, Volume 37, Issue 4, pp 4649–4654 | Cite as

RETRACTED ARTICLE: Overexpression of OCT4 contributes to progression of hepatocellular carcinoma

  • Gang Xu
  • Fuzhen Qi
  • Jianhuai Zhang
  • Jianbo Xu
  • Ting Shi
  • Yi Miao
Original Article


The abnormal change of octamer transcription factor 4 (OCT4) is associated with tumor progression; however, its effect on hepatocellular carcinoma (HCC) behavior remains unclear. The purpose of this study was to determine the correlation between HCC and OCT4. In the present study, IHC, western blot analysis, and QRT-PCR were performed to identify differentially expressed OCT4 in a series of HCC tissues and adjacent non-cancerous tissues. In addition, the functions of OCT4 on HCC progression were studied in vitro. Silencing of OCT4 with siRNA was performed in HCC cell lines, and the impact on proliferation, migration, and the EMT marker of HCC was analyzed. Our results found that OCT4 levels were significantly higher in HCC tissues compared with the adjacent non-cancerous tissues. Furthermore, OCT4 siRNA significantly reduced the proliferation rate of SMMC-7721 and HepG2 cells, inhibited the migration and inversion, and could reverse EMT in HCC cells, indicating that OCT4 plays a critical role in HCC progression. Our data suggest that the pathogenesis of human HCC may be mediated by OCT4, and thus, OCT4 could represent selective targets for the molecularly targeted treatments of HCC.


Hepatocellular carcinoma Octamer transcription factor 4 Epithelial-to-mesenchymal transition Proliferation Migration 


Conflicts of interest



  1. 1.
    Lin S, Hoffmann K, Schemmer P. Treatment of hepatocellular carcinoma: a systematic review. Liver Cancer. 2012;1:144–58.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Nishikawa H, Kimura T, Kita R, Osaki Y. Treatment for hepatocellular carcinoma in elderly patients: a literature review. J Cancer. 2013;4:635–43.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Murakami Y, Tamori A, Itami S, Tanahashi T, Toyoda H, Tanaka M, et al. The expression level of mir-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis. BMC Cancer. 2013;13:99.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    De Giorgi V, Buonaguro L, Worschech A, Tornesello ML, Izzo F, Marincola FM, et al. Molecular signatures associated with hcv-induced hepatocellular carcinoma and liver metastasis. PLoS One. 2013;8:e56153.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chiappini F. Circulating tumor cells measurements in hepatocellular carcinoma. Int J Hepatol. 2012;2012:684802.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kim RJ, Nam JS. OCT4 expression enhances features of cancer stem cells in a mouse model of breast cancer. Lab Anim Res. 2011;27:147–52.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK, Trsko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005;26:495–502.CrossRefPubMedGoogle Scholar
  8. 8.
    Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95:379–91.CrossRefPubMedGoogle Scholar
  9. 9.
    Asadi MH, Mowla SJ, Fathi F, Aleyasin A, Asadzadeh J, Atlasi Y. OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. Int J Cancer. 2011;128:2645–52.CrossRefPubMedGoogle Scholar
  10. 10.
    Chen Z, Xu WR, Qian H, Zhu W, Bu XF, Wang S, et al. Oct4, a novel marker for human gastric cancer. J Surg Oncol. 2009;99:414–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Zheng X, Vittar NB, Gai X, Fernandez-Barrena MG, Moser CD, Hu C, et al. The transcription factor GLI1 mediates TGFb1 driven EMT in hepatocellular carcinoma via a SNAI1-dependent mechanism. PLoS One. 2012;7:e49581.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Zhang S, Wang X, Iqbal S, Wang Y, Osunkoya AO, Chen Z, et al. Epidermal growth factor promotes protein degradation of epithelial protein lost in neoplasm (EPLIN), a putative metastasis suppressor, during epithelial–mesenchymal transition. J Biol Chem. 2012;288:1469–79.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lahsnig C, Mikula M, Petz M, Zulehner G, Schneller D, van Zijl F, et al. ILEI requires oncogenic Ras for the epithelial to mesenchymal transition of hepatocytes and liver carcinoma progression. Oncogene. 2009;28:638–50.CrossRefPubMedGoogle Scholar
  14. 14.
    He X. et al. Targeting the microRNA-21/AP1 axis by 5-fluorouracil and pirarubicin in human hepatocellular carcinoma. Oncotarget. 2014.Google Scholar
  15. 15.
    Babaie Y, Herwig R, Greber B, Brink TC, Wruck W, Groth D, et al. Analysis of Oct4-dependent transcriptional networks regulating selfrenewal and pluripotency in human embryonic stem cells. Stem Cells. 2007;25:500–10.CrossRefPubMedGoogle Scholar
  16. 16.
    Atlasi Y, Mowla SJ, Ziaee AM, Bahrami AR. OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. Int J Cancer. 2007;120:1598–602.CrossRefPubMedGoogle Scholar
  17. 17.
    Du Z, Jia D, Liu S, Wang F, Li G, Zhang Y, et al. Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia. 2009;57:724–33.CrossRefPubMedGoogle Scholar
  18. 18.
    Sotomayor P, Godoy A, Smith GJ, Huss WJ. Oct4 A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate. 2009;69:401–10.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Schreiber C, Kuch V, Umansky V, Sleeman JP. Autochthonous mouse melanoma and mammary tumors do not express the pluripotency genes Oct4 and Nanog. PLoS One. 2013;8:e57465.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Giovannini C et al. Suppression of p53 by Notch3 is mediated by Cyclin G1 and sustained by MDM2 and miR-221 axis in hepatocellular carcinoma. Oncotarget. 2014;5:10607–20.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zhou HC, Fang JH, Luo X, Zhang L, Yang J, Zhang C, et al. Downregulation of microRNA-100 enhances the ICMT-Rac1 signaling and promotes metastasis of hepatocellular carcinoma cells. Oncotarget. 2014;5:12177–88.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Gang Xu
    • 1
  • Fuzhen Qi
    • 1
  • Jianhuai Zhang
    • 1
  • Jianbo Xu
    • 1
  • Ting Shi
    • 1
  • Yi Miao
    • 2
  1. 1.Department of General SurgeryHuai’an First People’s Hospital, Nanjing Medical UniversityHuai’anChina
  2. 2.Department of General SurgeryFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Personalised recommendations