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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
December-2016 Volume 12 Issue 6

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
December-2016 Volume 12 Issue 6

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

Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2

  • Authors:
    • Zhong‑Yang Ding
    • Yun‑Juan Huang
    • Jian‑Dong Tang
    • Gan Li
    • Pan‑Qiang Jiang
    • Hao‑Tian Wu
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Wuxi Chinese Medicine Hospital Affiliated by Nanjing, Chinese Medicine University, Wuxi, Jiangsu 214023, P.R. China, Department of Nursery, Wuxi People's Hospital, Wuxi, Jiangsu 214023, P.R. China
  • Pages: 3735-3741
    |
    Published online on: October 20, 2016
       https://doi.org/10.3892/etm.2016.3826
  • 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

Adaptation to hypoxia is an important process physiologically and pathologically. Hypoxia-inducible factor-1α (HIF-1α) participates in the cancer biology of numerous endocrine tumors, including their proliferation and differentiation. In the present study, the hypothesis that HIF‑1α promotes tumorigenesis in thyroid cancer via upregulating angiogenesis-associated markers is investigated. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis were used to examine the expression of HIF‑1α in thyroid cancer cell lines, and to detect the expression of WW domain containing E3 ubiquitin protein ligase (WWP)2, WWP9, vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in MZ‑CRC‑1 and TT thyroid cancer cells. Cell proliferation was measured using a Cell Count Kit‑8. Cell apoptosis and cell cycle was assessed by flow cytometry. Cell invasive ability was examined by Matrigel transwell analysis. RT‑qPCR and western blot analyses demonstrated that the mRNA and protein expression levels of HIF‑1α were significant higher in MZ‑CRC‑1 and TT thyroid cancer cells than in another three thyroid cancer cells (P<0.01). HIF‑1α knockdown cells demonstrated inhibition of cell proliferation and invasion, arrested cell cycle at the G1 phase, and induction of cell apoptosis. The protein expression levels of WWP2, WWP9, VEGF and VEGFR2 were decreased in HIF‑1α knockdown MZ‑CRC‑1 and TT cells. In conclusion, HIF‑1α may be important in cell apoptosis and invasion of thyroid cancer cells, likely through regulating WWP2, WWP9, VEGF and VEGFR2 expression.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kondo T, Ezzat S and Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 6:292–306. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Sosa JA and Udelsman R: Papillary thyroid cancer. Surg Oncol Clin N Am. 15:585–601. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Hundahl SA, Fleming ID, Fremgen AM and Menck HR: A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the US, 1985–1995 [see comments]. Cancer. 83:2638–2648. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Marsh DJ, Learoyd DL and Robinson BG: Medullary thyroid carcinoma: Recent advances and management update. Thyroid. 5:407–424. 1995. View Article : Google Scholar : PubMed/NCBI

5 

Vaupel P: The role of hypoxia-induced factors in tumor progression. Oncologist. 99:(Suppl 5). S10–S17. 2004. View Article : Google Scholar

6 

Vleugel M, Greijer A, Shvarts A, van der Groep P, van Berkel M, Aarbodem Y, van Tinteren H, Harris AL, van Diest PJ and van der Wall E: Differential prognostic impact of hypoxia induced and diffuse HIF-1alpha expression in invasive breast cancer. J Clin Pathol. 58:172–177. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Kimbro KS and Simons JW: Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr Relat Cancer. 13:739–749. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Pouysségur J, Dayan F and Mazure NM: Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 441:437–443. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Amelio I and Melino G: The Sharp blade against HIF-mediated metastasis. Cell Cycle. 11:4530–4535. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Scarpino S, d'Alena F Cancellario, Di Napoli A, Pasquini A, Marzullo A and Ruco LP: Increased expression of Met protein is associated with up-regulation of hypoxia inducible factor-1 (HIF-1) in tumour cells in papillary carcinoma of the thyroid. J Pathol. 202:352–358. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Burrows N, Resch J, Cowen RL, von Wasielewski R, Hoang-Vu C, West CM, Williams KJ and Brabant G: Expression of hypoxia-inducible factor 1alpha in thyroid carcinomas. Endocr Relat Cancer. 17:61–72. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Yang QC, Zeng BF, Shi ZM, Dong Y, Jiang ZM, Huang J, Lv YM, Yang CX and Liu YW: Inhibition of hypoxia-induced angiogenesis by trichostatin A via suppression of HIF-1a activity in human osteosarcoma. J Exp Clin Cancer Res. 25:593–599. 2006.PubMed/NCBI

14 

Kyzas PA, Stefanou D, Batistatou A and Agnantis NJ: Hypoxia-induced tumor angiogenic pathway in head and neck cancer: An in vivo study. Cancer Lett. 225:297–304. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ioannou M, Papamichali R, Kouvaras E, Mylonis I, Vageli D, Kerenidou T, Barbanis S, Daponte A, Simos G, Gourgoulianis K and Koukoulis GK: Hypoxia inducible factor-1 alpha and vascular endothelial growth factor in biopsies of small cell lung carcinoma. Lung. 187:321–329. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Litz J and Krystal GW: Imatinib inhibits c-Kit-induced hypoxia-inducible factor-1alpha activity and vascular endothelial growth factor expression in small cell lung cancer cells. Mol Cancer Ther. 5:1415–1422. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Payton JE, Grieselhuber NR, Chang LW, Murakami M, Geiss GK, Link DC, Nagarajan R, Watson MA and Ley TJ: High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples. J Clin Invest. 119:1714–1726. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Harris AL: Hypoxia-a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Zagzag D, Zhong H, Scalzitti JM, Laughner E, Simons JW and Semenza GL: Expression of hypoxia-inducible factor 1alpha in brain tumors: Association with angiogenesis, invasion and progression. Cancer. 88:2606–2618. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Jensen RL, Ragel BT, Whang K and Gillespie D: Inhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas. J Neurooncol. 78:233–247. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J and Hong B: MiR-138 suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in clear cell renal cell carcinoma 786-O cells. Asian Pac J Cancer Prev. 12:1307–1311. 2011.PubMed/NCBI

22 

Chen B, Yuping S and Ni J: Rapamycin decreases survivin expression to induce NSCLC cell apoptosis under hypoxia through inhibiting HIF-1α induction. Mol Biol Rep. 39:185–191. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Ghafar MA, Anastasiadis AG, Chen MW, Burchardt M, Olsson LE, Xie H, Benson MC and Buttyan R: Acute hypoxia increases the aggressive characteristics and survival properties of prostate cancer cells. Prostate. 54:58–67. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Fan LF, Diao LM, Chen DJ, Liu MQ, Zhu LQ, Li HG, Tang ZJ, Xia D, Liu X and Chen HL: Expression of HIF-1 alpha and its relationship to apoptosis and proliferation in lung cancer. Ai Zheng. 21:254–258. 2002.(In Chinese). PubMed/NCBI

25 

Victor N, Ivy A, Jiang BH and Agani FH: Involvement of HIF-1 in invasion of Mum2B uveal melanoma cells. Clin Exp Metastasis. 23:87–96. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Chang C and Werb Z: The many faces of metalloproteases: Cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 11:S37–S43. 2001. View Article : Google Scholar : PubMed/NCBI

27 

John A and Tuszynski G: The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res. 7:14–23. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Carmeliet P: VEGF as a key mediator of angiogenesis in cancer. Oncology. 69:(Suppl 3). S4–S10. 2005. View Article : Google Scholar

29 

Poulaki V, Mitsiades CS, McMullan C, Sykoutri D, Fanourakis G, Kotoula V, Tseleni-Balafouta S, Koutras DA and Mitsiades N: Regulation of vascular endothelial growth factor expression by insulin-like growth factor I in thyroid carcinomas. J Clin Endocrinol Metab. 88:5392–5398. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Gonzalez-Perez RR, Xu Y, Guo S, Watters A, Zhou W and Leibovich SJ: Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFkappaB/HIF-1alpha activation. Cell Signal. 22:1350–1362. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ding ZY, Huang YJ, Tang JD, Li G, Jiang PQ and Wu HT: Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2. Exp Ther Med 12: 3735-3741, 2016.
APA
Ding, Z., Huang, Y., Tang, J., Li, G., Jiang, P., & Wu, H. (2016). Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2. Experimental and Therapeutic Medicine, 12, 3735-3741. https://doi.org/10.3892/etm.2016.3826
MLA
Ding, Z., Huang, Y., Tang, J., Li, G., Jiang, P., Wu, H."Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2". Experimental and Therapeutic Medicine 12.6 (2016): 3735-3741.
Chicago
Ding, Z., Huang, Y., Tang, J., Li, G., Jiang, P., Wu, H."Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2". Experimental and Therapeutic Medicine 12, no. 6 (2016): 3735-3741. https://doi.org/10.3892/etm.2016.3826
Copy and paste a formatted citation
x
Spandidos Publications style
Ding ZY, Huang YJ, Tang JD, Li G, Jiang PQ and Wu HT: Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2. Exp Ther Med 12: 3735-3741, 2016.
APA
Ding, Z., Huang, Y., Tang, J., Li, G., Jiang, P., & Wu, H. (2016). Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2. Experimental and Therapeutic Medicine, 12, 3735-3741. https://doi.org/10.3892/etm.2016.3826
MLA
Ding, Z., Huang, Y., Tang, J., Li, G., Jiang, P., Wu, H."Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2". Experimental and Therapeutic Medicine 12.6 (2016): 3735-3741.
Chicago
Ding, Z., Huang, Y., Tang, J., Li, G., Jiang, P., Wu, H."Silencing of hypoxia-inducible factor-1α promotes thyroid cancer cell apoptosis and inhibits invasion by downregulating WWP2, WWP9, VEGF and VEGFR2". Experimental and Therapeutic Medicine 12, no. 6 (2016): 3735-3741. https://doi.org/10.3892/etm.2016.3826
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