Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
2014-April Volume 31 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
2014-April Volume 31 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

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 / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China, PLA Center of General Surgery, General Hospital of Chengdu Army Region, Chengdu, Sichuan 610083, P.R. China, Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
  • Pages: 1911-1920
    |
    Published online on: February 20, 2014
       https://doi.org/10.3892/or.2014.3043
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



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.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

View References

1 

Shiozawa Y, Nie B, Pienta KJ, Morgan TM and Taichman RS: Cancer stem cells and their role in metastasis. Pharmacol Ther. 138:285–293. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Cheng X and O’Neill HC: Oncogenesis and cancer stem cells: current opinions and future directions. J Cell Mol Med. 13:4377–4384. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Yamashita T and Wang XW: Cancer stem cells in the development of liver cancer. J Clin Invest. 123:1911–1918. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Padhya KT, Marrero JA and Singal AG: Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 29:285–292. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Wilson GS, Hu Z, Duan W, et al: Efficacy of using cancer stem cell markers in isolating and characterizing liver cancer stem cells. Stem Cells Dev. 22:2655–2664. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Lee H, Kim JB, Park SY, Kim SS and Kim H: Combination effect of paclitaxel and hyaluronic acid on cancer stem-like side population cells. J Biomed Nanotechnol. 9:299–302. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Zheng L, Liang P, Li J, et al: ShRNA-targeted COMMD7 suppresses hepatocellular carcinoma growth. PLoS One. 7:e454122012. View Article : Google Scholar : PubMed/NCBI

8 

Zheng L, Huang X, Liang P, et al: BC047440 overexpression is a risk factor for tumor invasion and poor prognosis in hepatocellular carcinoma. Hepatogastroenterology. 57:919–925. 2010.PubMed/NCBI

9 

Zheng L, Liang P, Zhou J, Huang X, Wen Y, Wang Z and Li J: BC047440 antisense eukaryotic expression vectors inhibited HepG2 cell proliferation and suppressed xenograft tumorigenicity. Braz J Med Biol Res. 45:97–103. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Liu WH, Li R and Dou KF: Convenient and efficient enrichment of the CD133+ liver cells from rat fetal liver cells as a source of liver stem/progenitor cells. Stem Cell Rev. 7:94–102. 2011.PubMed/NCBI

11 

Liu WH, Wang X, You N, et al: Efficient enrichment of hepatic cancer stem-like cells from a primary rat HCC model via a density gradient centrifugation-centered method. PLoS One. 7:e357202012. View Article : Google Scholar : PubMed/NCBI

12 

Li CH, Wang YJ, Dong W, et al: Hepatic oval cell lines generate hepatocellular carcinoma following transfection with HBx gene and treatment with aflatoxin B1 in vivo. Cancer Lett. 311:1–10. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Chiba T, Kita K, Zheng YW, et al: Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties. Hepatology. 44:240–245. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J and Li J: Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer. 126:2067–2078. 2010.PubMed/NCBI

15 

Espandiari P, Robertson LW, Srinivasan C and Glauert HP: Comparison of different initiation protocols in the resistant hepatocyte model. Toxicology. 206:373–381. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Yamashita T, Honda M, Nakamoto Y, et al: Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma. Hepatology. 57:1484–1497. 2013.PubMed/NCBI

17 

Malanchi I, Peinado H, Kassen D, et al: Cutaneous cancer stem cell maintenance is dependent on β-catenin signalling. Nature. 452:650–653. 2008.

18 

Zhao C, Chen A, Jamieson CH, et al: Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature. 458:776–779. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Viale A, De Franco F, Orleth A, et al: Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature. 457:51–56. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Cui H, Hu B, Li T, Ma J, Alam G, Gunning WT and Ding HF: Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. Am J Pathol. 170:1370–1378. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Kim JH, Yoon SY, Kim CN, et al: The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins. Cancer Lett. 203:217–224. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Song K, Wu J and Jiang C: Dysregulation of signaling pathways and putative biomarkers in liver cancer stem cells (Review). Oncol Rep. 29:3–12. 2013.PubMed/NCBI

23 

Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM and Eberhart CG: Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 66:7445–7452. 2006. View Article : Google Scholar

24 

Verma UN, Surabhi RM, Schmaltieg A, Becerra C and Gaynor RB: Small interfering RNAs directed against β-catenin inhibit the in vitro and in vivo growth of colon cancer cells. Clin Cancer Res. 9:1291–1300. 2003.

25 

Piccirillo SG, Reynolds BA, Zanetti N, et al: Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 444:761–765. 2006. View Article : Google Scholar : PubMed/NCBI

26 

DiDonato JA, Mercurio F and Karin M: NF-κB and the link between inflammation and cancer. Immunol Rev. 246:379–400. 2012.

27 

Prud’homme GJ: Cancer stem cells and novel targets for antitumor strategies. Curr Pharm Des. 18:2838–2849. 2012.PubMed/NCBI

28 

Ning BF, Ding J, Yin C, et al: Hepatocyte nuclear factor 4α suppresses the development of hepatocellular carcinoma. Cancer Res. 70:7640–7651. 2010.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
You N, Zheng L, Liu W, Zhong X, Wang W and 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. Oncol Rep 31: 1911-1920, 2014.
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
Copy and paste a formatted citation
x
Spandidos Publications style
You N, Zheng L, Liu W, Zhong X, Wang W and 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. Oncol Rep 31: 1911-1920, 2014.
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
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team