Proliferation inhibition and differentiation induction of hepatic cancer stem cells by knockdown of BC047440: A potential therapeutic target of stem cell treatment for hepatocellular carcinoma

  • Authors:
    • Nan You
    • Lu Zheng
    • Weihui Liu
    • Xiao Zhong
    • Weiwei Wang
    • Jing Li
  • View Affiliations

  • Published online on: February 20, 2014     https://doi.org/10.3892/or.2014.3043
  • Pages: 1911-1920
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Abstract

Recent findings suggest that clinical hepatocellular carcinoma (HCC) progression is driven by hepatic cancer stem cells (HCSCs) through their capacity for self-renewal, generation of heterogeneous lineages of cancer cells, resistance to chemotherapy and their ability to divide limitlessly, which may contribute to the failure of existing therapies to consistently eradicate malignant tumors. Therefore, HCSC-directed therapeutic approaches might represent strategies to improve clinical HCC therapy. In previous studies, we showed that BC047440 was found to play a critical role in mediating HCC cell proliferation. The present study sought to determine whether BC047440 is involved in maintaining HCSC malignant behavior (including proliferation and differentiation). We demonstrated that BC047440 expression was markedly upregulated in HCSCs. Furthermore, we inhibited BC047440 in HCSCs using short hairpin RNA (shRNA). The effects of BC047440 on proliferation and differentiation were investigated. We also analyzed the involvement of critical molecular events known to regulate the proliferation and the differentiation machinery. Excluding apoptosis-related effects, we found that BC047440 inhibition resulted in enhanced cell proliferation through enhancing cytoplasmic accumulation of nuclear factor-κB (NF-κB) with a concomitant decrease in the nuclear fraction. BC047440 inhibition also resulted in inducing HCSC differentiation into hepatocytes. Furthermore, following downregulation of BC047440, the level of hepatocyte nuclear factor 4α (HNF4α) increased. Finally, tumorigenicity suppression following BC047440 depletion was confirmed in a nude mouse model. In conclusion, our findings indicate that BC047440 plays an important role in the proliferation and differentiation of HCSCs and may represent a novel therapeutic target for the treatment of HCC.

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April 2014
Volume 31 Issue 4

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Copy and paste a formatted citation
APA
You, N., Zheng, L., Liu, W., Zhong, X., Wang, W., & Li, J. (2014). Proliferation inhibition and differentiation induction of hepatic cancer stem cells by knockdown of BC047440: A potential therapeutic target of stem cell treatment for hepatocellular carcinoma. Oncology Reports, 31, 1911-1920. https://doi.org/10.3892/or.2014.3043
MLA
You, N., Zheng, L., Liu, W., Zhong, X., Wang, W., Li, J."Proliferation inhibition and differentiation induction of hepatic cancer stem cells by knockdown of BC047440: A potential therapeutic target of stem cell treatment for hepatocellular carcinoma". Oncology Reports 31.4 (2014): 1911-1920.
Chicago
You, N., Zheng, L., Liu, W., Zhong, X., Wang, W., Li, J."Proliferation inhibition and differentiation induction of hepatic cancer stem cells by knockdown of BC047440: A potential therapeutic target of stem cell treatment for hepatocellular carcinoma". Oncology Reports 31, no. 4 (2014): 1911-1920. https://doi.org/10.3892/or.2014.3043