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
August-2019 Volume 42 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
August-2019 Volume 42 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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes

  • Authors:
    • Rui Xu
    • Lin Chen
    • Wen‑Ting Yang
  • View Affiliations / Copyright

    Affiliations: Department of Reproductive Medicine, The First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Pathology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710061, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 688-696
    |
    Published online on: June 6, 2019
       https://doi.org/10.3892/or.2019.7188
  • 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

The exact molecular mechanisms underlying cervical tumorigenesis are poorly understood. Polycomb complex protein Bmi1 (Bmi1) is involved in the malignant transformation and biological aggressiveness of several human carcinomas. Therefore, the present study assessed the expression of Bmi1 protein in human cervical cancer tissues and examined the mechanisms involved in cervical carcinogenesis. The expression of Bmi1 protein was examined by immunohistochemistry in cervical carcinoma tissues (n=71), high‑grade squamous intraepithelial lesions (n=41) and normal cervical tissues (n=47). Expression of Bmi1 protein gradually increased across samples from the normal cervix (1/47; 2.12%), high‑grade squamous intraepithelial lesions (5/42; 16.13%) and cervical carcinomas (31/71; 43.66%; P<0.05). Additionally, Bmi1 protein expression was associated with tumor histopathological grade. The effects of Bmi1 silencing and overexpression on tumor sphere formation and the tumorigenicity of cervical cancer cells were investigated. Overexpression of Bmi1 resulted in significantly attenuated tumor formation and tumor sphere formation. Consistently, Bmi1 silencing significantly inhibited tumor formation and tumor sphere formation. Furthermore, Bmi1 upregulated the expression of Sox2, and the dual‑luciferase reporter assay and chromatin immunoprecipitation showed that Bmi1 transactivated Sox2 by binding to the two E‑box motifs in the Sox2 promoter. In conclusion, aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes as a potential oncogenic factor that participates in the carcinogenesis of cervical carcinomas.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Dick JE: Breast cancer stem cells revealed. Proc Natl Acad Sci USA. 100:3547–3549. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Graham SM, Jørgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L and Holyoake TL: Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 99:319–325. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, et al: CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 120:485–497. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH and Weissman IL: Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA. 97:14720–14725. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Rountree CB, Ding W, He L and Stiles B: Expansion of CD133-expressing liver cancer stem cells in liver-specific phosphatase and tensin homolog deleted on chromosome 10-deleted mice. Stem Cells. 27:290–299. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Paavonen J: Human papillomavirus infection and the development of cervical cancer and related genital neoplasias. Int J Infect Dis. 11 (Suppl 2):S3–S9. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ and Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 189:12–19. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Molofsky AV, He S, Bydon M, Morrison SJ and Pardal R: Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 19:1432–1437. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Bertolini JA, Favaro R, Zhu Y, Pagin M, Ngan CY, Wong CH, Tjong H, Vermunt MW, Martynoga B, Barone C, et al: Mapping the global chromatin connectivity network for Sox2 function in neural stem cell maintenance. Cell Stem Cell. 24:462–476.e6. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Douglas D, Hsu JH, Hung L, Cooper A, Abdueva D, van Doorninck J, Peng G, Shimada H, Triche TJ and Lawlor ER: BMI-1 promotes ewing sarcoma tumorigenicity independent of CDKN2A repression. Cancer Res. 68:6507–6515. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Spremović-Rađenović S, Stefanović A, Kadija S, Jeremić K and Sparić R: Classification and the diagnostics of abnormal uterine bleeding in nongravid women of reproductive age: The PALM-COEIN classification system adopted by the international federation of gynecology and obstetrics. Vojnosanit Pregl. 73:1154–1159. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Guo WJ, Zeng MS, Yadav A, Song LB, Guo BH, Band V and Dimri GP: Mel-18 acts as a tumor suppressor by repressing Bmi-1 expression and down-regulating Akt activity in breast cancer cells. Cancer Res. 67:5083–5089. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Xu R, Yang WT and Zheng PS: Coexpression of B-lymphoma Moloney murine leukemia virus insertion region-1 and sex-determining region of Y chromosome-related high mobility group box-2 in cervical carcinogenesis. Hum Pathol. 44:208–217. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Liu XF, Yang WT, Xu R, Liu JT and Zheng PS: Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells. PLoS One. 9:e870922014. View Article : Google Scholar : PubMed/NCBI

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Wiederschain D, Chen L, Johnson B, Bettano K, Jackson D, Taraszka J, Wang YK, Jones MD, Morrissey M, Deeds J, et al: Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis. Mol Cell Biol. 27:4968–4979. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Kim JH, Yoon SY, Jeong SH, Kim SY, Moon SK, Joo JH, Lee Y, Choe IS and Kim JW: Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast. 13:383–388. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE, Amin HM, Ward DC and Ma Y: Bi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci USA. 104:10494–10499. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Valk-Lingbeek ME, Bruggeman SW and van Lohuizen M: Stem cells and cancer; the polycomb connection. Cell. 118:409–418. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Lessard J and Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 423:255–260. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Vonlanthen S, Heighway J, Altermatt HJ, Gugger M, Kappeler A, Borner MM, van Lohuizen M and Betticher DC: The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer. 84:1372–1376. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Wang Y, He SS, Cai XY, Chen HY, Yang XL, Lu LX and Chen Y: The novel prognostic score combining red blood cell distribution width and body mass index (COR-BMI) has prognostic impact for survival outcomes in nasopharyngeal carcinoma. J Cancer. 9:2295–2301. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Wu J, Hu D, Yang G, Zhou J, Yang C, Gao Y and Zhu Z: Down-regulation of BMI-1 cooperates with artemisinin on growth inhibition of nasopharyngeal carcinoma cells. J Cell Biochem. 112:1938–1948. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Peters WM: Nature of ‘basal’ and ‘reserve’ cells in oviductal and cervical epithelium in man. J Clin Pathol. 39:306–312. 1986. View Article : Google Scholar : PubMed/NCBI

28 

Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, Jackson KW, Suri P and Wicha MS: Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66:6063–6071. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Ji J and Zheng PS: Expression of Sox2 in human cervical carcinogenesis. Hum Pathol. 41:1438–1447. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Maurizi G, Verma N, Gadi A, Mansukhani A and Basilico C: Sox2 is required for tumor development and cancer cell proliferation in osteosarcoma. Oncogene. 37:4626–4632. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Andreu-Agullo C, Maurin T, Thompson CB and Lai EC: Ars2 maintains neural stem-cell identity through direct transcriptional activation of Sox2. Nature. 481:195–198. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Miyagi S, Nishimoto M, Saito T, Ninomiya M, Sawamoto K, Okano H, Muramatsu M, Oguro H, Iwama A and Okuda A: The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. J Biol Chem. 281:13374–13381. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Danopoulos S, Alonso I, Thornton ME, Grubbs BH, Bellusci S, Warburton D and Al Alam D: Human lung branching morphogenesis is orchestrated by the spatiotemporal distribution of ACTA2, SOX2, and SOX9. Am J Physiol Lung Cell Mol Physiol. 314:L144–L149. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Gontan C, de Munck A, Vermeij M, Grosveld F, Tibboel D and Rottier R: Sox2 is important for two crucial processes in lung development: Branching morphogenesis and epithelial cell differentiation. Dev Biol. 317:296–309. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xu R, Chen L and Yang WT: Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes. Oncol Rep 42: 688-696, 2019.
APA
Xu, R., Chen, L., & Yang, W. (2019). Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes. Oncology Reports, 42, 688-696. https://doi.org/10.3892/or.2019.7188
MLA
Xu, R., Chen, L., Yang, W."Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes". Oncology Reports 42.2 (2019): 688-696.
Chicago
Xu, R., Chen, L., Yang, W."Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes". Oncology Reports 42, no. 2 (2019): 688-696. https://doi.org/10.3892/or.2019.7188
Copy and paste a formatted citation
x
Spandidos Publications style
Xu R, Chen L and Yang WT: Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes. Oncol Rep 42: 688-696, 2019.
APA
Xu, R., Chen, L., & Yang, W. (2019). Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes. Oncology Reports, 42, 688-696. https://doi.org/10.3892/or.2019.7188
MLA
Xu, R., Chen, L., Yang, W."Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes". Oncology Reports 42.2 (2019): 688-696.
Chicago
Xu, R., Chen, L., Yang, W."Aberrantly elevated Bmi1 promotes cervical cancer tumorigenicity and tumor sphere formation via enhanced transcriptional regulation of Sox2 genes". Oncology Reports 42, no. 2 (2019): 688-696. https://doi.org/10.3892/or.2019.7188
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