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
February-2015 Volume 33 Issue 2

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
February-2015 Volume 33 Issue 2

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

HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α

  • Authors:
    • Juan-Juan Chen
    • Yi-Shu Tang
    • Shi-Feng Huang
    • Jian-Gang Ai
    • Hai-Xia Wang
    • Li-Ping Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
  • Pages: 792-798
    |
    Published online on: December 4, 2014
       https://doi.org/10.3892/or.2014.3647
  • 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

Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). Emerging evidence has shown the association between aberrantly expressed miR-221 and cancer development; however, little is known concerning its potential role in hepatitis B virus (HBV)-related HCC. In the present study, functional studies demonstrated that HBx leads to the promotion of cell proliferation and cell growth viability. Obviously overexpressed miR-221 was found in HBx-transfected cells compared with the mock counterparts. Suppression of miR-221 significantly inhibited HCC cell proliferation. Western blot analysis indicated that estrogen receptor-α (ERα) was downregulated in HCC tissues and cell lines. Bioinformatic analysis combined with validation experiments identified ERα as a direct target of miR-221. The present study suggests that miR-221 modulates HCC cancer cell proliferation by suppressing ERα, functioning as a tumor promoter. Moreover, our data imply that miR-221 has potential as an miRNA-based therapeutic target for HBV-related HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Sangiovanni A, Del Ninno E, Fasani P, et al: Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 126:1005–1014. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Han Z: Recent progress in genomic [corrected] research of liver cancer. Sci China C Life Sci. 52:24–30. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Lavanchy D: Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 11:97–107. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Neuveut C, Wei Y and Buendia MA: Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol. 52:594–604. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Ng SA and Lee C: Hepatitis B virus X gene and hepatocarcinogenesis. J Gastroenterol. 46:974–990. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Brenneck J, Hipfner DR, Stark A, et al: bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 113:25–36. 2003. View Article : Google Scholar

9 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Shi XB, Tepper CG and deVere White RW: Cancerous miRNAs and their regulation. Cell Cycle. 7:1529–1538. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Santhekadur PK, Das SK, Gredler R, et al: Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor κB and miR-221. J Biol Chem. 287:13952–13958. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Park JK, Koqure T, Nuovo GJ, et al: miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res. 71:7608–7616. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Ogawa T, Enomoto M, Fujii H, et al: MicroRNA-221/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis. Gut. 61:1600–1609. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Naugler WE, Sakurai T, Kim S, et al: Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 317:121–124. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Zhao JJ, Lin J, Yang H, et al: MicroRNA-221/222 negatively regulates estrogen receptor α and is associated with tamoxifen resistance in breast cancer. J Biol Chem. 283:31079–31086. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Acs G, Sells MA, Purcell RH, et al: Hepatitis B virus produced by transfected HepG2 cells causes hepatitis in chimpanzees. Proc Natl Acad Sci USA. 84:4641–4644. 1987. View Article : Google Scholar

17 

Sells MA, Chen ML and Acs G: Production of hepatitis B virus particles in HepG2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci USA. 84:1005–1009. 1987. View Article : Google Scholar

18 

Mott JL, Kobayashi S, Bronk SF and Gores GJ: miR-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 26:6133–6140. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Roderburq C, Urban GW, Bettermann K, et al: Micro-RNA profiling reveals a role of miR-29 in human and murine liver fibrosis. Hepatology. 53:209–218. 2011. View Article : Google Scholar

20 

Pineau P, Volinia S, McJunkin K, et al: miR-221 overexpression contributes to liver tumorigenesis. Proc Natl Acad Sci USA. 107:264–269. 2010. View Article : Google Scholar :

21 

Gramantieri L, Ferracin M, Formari F, et al: Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 67:6092–6099. 2007. View Article : Google Scholar : PubMed/NCBI

22 

le Sage C, Nagel R, Egan DA, et al: Regulation of the p27Kip1 tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 26:3699–3708. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Medina R, Zaidi SK, Liu CG, et al: MicroRNAs 221 and 222 bypass quiescence and compromise cell suvival. Cancer Res. 68:2773–2780. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Rehman SK, Li SH, Wyszomierski SL, et al: 14-3-3ζ orchestrates mammary tumor onset and progression via miR-221-mediated cell proliferation. Cancer Res. 74:363–373. 2014. View Article : Google Scholar :

25 

Su A, He S, Tian B, et al: MicroRNA-221 mediates the effects of PDGF-BB on migration, proliferation, and the epithelial-mesenchymal transition in pancreatic cancer cells. PLoS One. 8:e713092013. View Article : Google Scholar : PubMed/NCBI

26 

Rommer A, Steinleitner K, Hackl H, et al: Overexpression of primary microRNA 221/222 in acute myeloid leukemia. BMC Cancer. 13:3642013. View Article : Google Scholar : PubMed/NCBI

27 

Yu MW, Chang HC, Chang SC, et al: Role of reproductive factors in hepatocellular carcinoma: impact on hepatitis B- and C-related risk. Hepatology. 38:1393–1400. 2003.PubMed/NCBI

28 

Vesselinovitch SD, Itze L, Mihailovich N and Rao KV: Modifying role of partial hepatectomy and gonadectomy in ethylnitrosourea-induced hepatocarcinogenesis. Cancer Res. 40:1538–1542. 1980.PubMed/NCBI

29 

Nakatani T, Roy G, Fujimoto N, et al: Sex hormone dependency of diethylnitrosamine-induced liver tumors in mice and chemoprevention by leuprorelin. Jpn J Cancer Res. 92:249–256. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Ng IO, Ng M and Fan ST: Better survival in woman with respected hepatocellular carcinoma is not related to tumor proliferation or expression of hormone receptors. Am J Gastroenterol. 92:1355–1358. 1997.PubMed/NCBI

31 

Jonas S, Bechstein WO, Heinze T, et al: Female sex hormone receptor status in advanced hepatocellular carcinoma and outcome after surgical resection. Surgery. 121:456–461. 1997. View Article : Google Scholar : PubMed/NCBI

32 

Nagasue N, Kohno H, Chang YC, et al: Clinicopathologic comparisons between estrogen receptor-positive and -negative hepatocellular carcinomas. Ann Surg. 212:150–154. 2009. View Article : Google Scholar

33 

Liu WH, Yeh SH, Lu CC, et al: MicroRNA-18a prevents estrogen receptor-α expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology. 136:683–693. 2009. View Article : Google Scholar

34 

Shen L, Ahuja N, Shen Y, et al: DNA methylation and environmental exposures in human hepatocellular carcinoma. J Natl Cancer Inst. 94:755–761. 2002. View Article : Google Scholar : PubMed/NCBI

35 

Pike MC and Spicer DV: Hormonal contraception and chemoprevention of female cancers. Endocr Relat Cancer. 7:73–83. 2000. View Article : Google Scholar : PubMed/NCBI

36 

Dutertre M and Smith CL: Molecular mechanisms of selective estrogen receptor modulator (SERM) action. J Pharmacol Exp Ther. 295:431–437. 2000.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen J, Tang Y, Huang S, Ai J, Wang H and Zhang L: HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α. Oncol Rep 33: 792-798, 2015.
APA
Chen, J., Tang, Y., Huang, S., Ai, J., Wang, H., & Zhang, L. (2015). HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α. Oncology Reports, 33, 792-798. https://doi.org/10.3892/or.2014.3647
MLA
Chen, J., Tang, Y., Huang, S., Ai, J., Wang, H., Zhang, L."HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α". Oncology Reports 33.2 (2015): 792-798.
Chicago
Chen, J., Tang, Y., Huang, S., Ai, J., Wang, H., Zhang, L."HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α". Oncology Reports 33, no. 2 (2015): 792-798. https://doi.org/10.3892/or.2014.3647
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Tang Y, Huang S, Ai J, Wang H and Zhang L: HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α. Oncol Rep 33: 792-798, 2015.
APA
Chen, J., Tang, Y., Huang, S., Ai, J., Wang, H., & Zhang, L. (2015). HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α. Oncology Reports, 33, 792-798. https://doi.org/10.3892/or.2014.3647
MLA
Chen, J., Tang, Y., Huang, S., Ai, J., Wang, H., Zhang, L."HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α". Oncology Reports 33.2 (2015): 792-798.
Chicago
Chen, J., Tang, Y., Huang, S., Ai, J., Wang, H., Zhang, L."HBx protein-induced upregulation of microRNA-221 promotes aberrant proliferation in HBV‑related hepatocellular carcinoma by targeting estrogen receptor-α". Oncology Reports 33, no. 2 (2015): 792-798. https://doi.org/10.3892/or.2014.3647
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