Abstract
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.
Similar content being viewed by others
References
Lin S, Hoffmann K, Schemmer P. Treatment of hepatocellular carcinoma: a systematic review. Liver Cancer. 2012;1:144–58.
Nishikawa H, Kimura T, Kita R, Osaki Y. Treatment for hepatocellular carcinoma in elderly patients: a literature review. J Cancer. 2013;4:635–43.
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.
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.
Chiappini F. Circulating tumor cells measurements in hepatocellular carcinoma. Int J Hepatol. 2012;2012:684802.
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.
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.
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.
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.
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.
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.
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.
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.
He X. et al. Targeting the microRNA-21/AP1 axis by 5-fluorouracil and pirarubicin in human hepatocellular carcinoma. Oncotarget. 2014.
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.
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.
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.
Sotomayor P, Godoy A, Smith GJ, Huss WJ. Oct4 A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate. 2009;69:401–10.
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.
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.
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.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Additional information
The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.
An erratum to this article is available at http://dx.doi.org/10.1007/s13277-017-5487-6.
About this article
Cite this article
Xu, G., Qi, F., Zhang, J. et al. RETRACTED ARTICLE: Overexpression of OCT4 contributes to progression of hepatocellular carcinoma. Tumor Biol. 37, 4649–4654 (2016). https://doi.org/10.1007/s13277-015-4285-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4285-2