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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
February-2019 Volume 19 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-2019 Volume 19 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 Open Access

Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics

  • Authors:
    • Wei‑Na Zhou
    • Yi‑Fei Du
    • Yang Zheng
    • Wei Zhang
    • Yu‑Nong Wu
    • Xiao‑Meng Song
    • Jin Bai
  • View Affiliations / Copyright

    Affiliations: Jiangsu Key Laboratory of Oral Diseases, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Jiangsu Center for The Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 885-894
    |
    Published online on: November 29, 2018
       https://doi.org/10.3892/mmr.2018.9705
  • 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 function of runt‑related transcription factor 3 (RUNX3) in oral cancer remains controversial. The present study aimed to determine the status of RUNX3 protein expression and its association with clinicopathological characteristics in tongue squamous cell carcinomas (SCC). The present study used three pairs of tongue SCC and non‑cancerous tissues to assess RUNX3 protein expression by western blot analysis, and two tongue SCC cell lines to determine RUNX3 protein localization by immunofluorescence and immunocytochemistry. Tissue microarray immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 79 patients with tongue SCC. The results demonstrated that RUNX3 protein expression was reduced in tongue SCC tissues compared with in paired non‑cancerous tissues. Similarly, the expression of RUNX3 was low in SCC25 and Cal27 cells, and was predominantly localized to the cytoplasm. In the 79 patients with tongue SCC, RUNX3 protein expression was presented in different manners in carcinoma nests and tumor stroma. RUNX3 in carcinoma nests (nRUNX3) exhibited nuclear positive staining in 24/79 samples, cytoplasmic mislocalization in 41/79 samples and was undetectable in 14/79 samples. RUNX3 in stroma (sRUNX3) exhibited nuclear positive staining in 40/79 samples and nuclear negative staining in 39/79 samples. Negative nRUNX3 expression was significantly associated with lymph node metastasis (P=0.014), clinical stage (P=0.027), and overall and disease‑free survival (P=0.008 and P=0.007, respectively). In addition, negative sRUNX3 expression was associated with lymph node metastasis (P=0.003) and clinical stage (P=0.003); however, not with overall survival. The findings of the present study preliminarily suggested that cytoplasmic mislocalization of RUNX3 protein may be a common event in tongue SCC, and that sRUNX3 protein expression may be a potential prognostic biomarker.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Scully C and Bagan J: Oral squamous cell carcinoma: Overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis. 15:388–399. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Weatherspoon DJ, Chattopadhyay A, Boroumand S and Garcia I: Oral cavity and oropharyngeal cancer incidence trends and disparities in the United States: 2000–2010. Cancer Epidemiol. 39:497–504. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Ng JH, Iyer NG, Tan MH and Edgren G: Changing epidemiology of oral squamous cell carcinoma of the tongue: A global study. Head Neck. 39:297–304. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Ghantous Y, Yaffi V and Abu-Elnaaj I: Oral cavity cancer: Epidemiology and early diagnosis. Refuat Hapeh Vehashinayim (1993). 3255–63. (71)2015.(In Hebrew). PubMed/NCBI

5 

Hanai J, Chen LF, Kanno T, Ohtani-Fujita N, Kim WY, Guo WH, Imamura T, Ishidou Y, Fukuchi M, Shi MJ, et al: Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter. J Biol Chem. 274:31577–31582. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Subramaniam MM, Chan JY, Yeoh KG, Quek T, Ito K and Salto-Tellez M: Molecular pathology of RUNX3 in human carcinogenesis. Biochim Biophys Acta. 1796:315–331. 2009.PubMed/NCBI

7 

Ito Y: Oncogenic potential of the RUNX gene family: ‘Overview’. Oncogene. 23:4198–4208. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Tonomoto Y, Tachibana M, Dhar DK, Onoda T, Hata K, Ohnuma H, Tanaka T and Nagasue N: Differential expression of RUNX genes in human esophageal squamous cell carcinoma: Downregulation of RUNX3 worsens patient prognosis. Oncology. 73:346–356. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Ito K, Liu Q, Salto-Tellez M, Yano T, Tada K, Ida H, Huang C, Shah N, Inoue M, Rajnakova A, et al: RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization. Cancer Res. 65:7743–7750. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Soong R, Shah N, Peh BK, Chong PY, Ng SS, Zeps N, Joseph D, Salto-Tellez M, Iacopetta B and Ito Y: The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome. Br J Cancer. 100:676–679. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Yu GP, Ji Y, Chen GQ, Huang B, Shen K, Wu S and Shen ZY: Application of RUNX3 gene promoter methylation in the diagnosis of non-small cell lung cancer. Oncol Lett. 3:159–162. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C, et al: RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res. 66:6512–6520. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Bai J, Yong HM, Chen FF, Song WB, Li C, Liu H and Zheng JN: RUNX3 is a prognostic marker and potential therapeutic target in human breast cancer. J Cancer Res Clin Oncol. 139:1813–1823. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Kim BR, Kang MH, Kim JL, Na YJ, Park SH, Lee SI, Kang S, Joung SY, Lee SY, Lee DH, et al: RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer. Oncol Rep. 36:2601–2608. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Chen H, Wang Z, Wang S, Zhang Z and Shi S: Effect and mechanism of RUNX3 gene on biological characteristics of human esophageal squamous cell carcinoma (ESCC). Med Oncol. 32:3572015. View Article : Google Scholar : PubMed/NCBI

16 

Mei PJ, Bai J, Liu H, Li C, Wu YP, Yu ZQ and Zheng JN: RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration. J Cancer Res Clin Oncol. 137:1823–1830. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Adelstein D, Gillison ML, Pfister DG, Spencer S, Adkins D, Brizel DM, Burtness B, Busse PM, Caudell JJ, Cmelak AJ, et al: NCCN guidelines insights: Head and neck cancers, version 2.2017. J Natl Compr Canc Netw. 15:761–770. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Zhou WN, Du YF, Bai J, Song XM, Zheng Y, Yuan H, Zhang W, Zhang ZD and Wu YN: RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma. Oncol Rep. 38:2378–2386. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Gao F, Huang C, Lin M, Wang Z, Shen J, Zhang H, Jiang L and Chen Q: Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas. J Cancer Res Clin Oncol. 135:739–747. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Myers JN, Elkins T, Roberts D and Byers RM: Squamous cell carcinoma of the tongue in young adults: Increasing incidence and factors that predict treatment outcomes. Otolaryngol Head Neck Surg. 122:44–51. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Lefeuvre M, Gunduz M, Nagatsuka H, Gunduz E, Al Sheikh Ali M, Beder L, Fukushima K, Yamanaka N, Shimizu K and Nagai N: Fine deletion analysis of 1p36 chromosomal region in oral squamous cell carcinomas. J Oral Pathol Med. 38:94–98. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Chen F, Liu X, Bai J, Pei D and Zheng J: The emerging role of RUNX3 in cancer metastasis (Review). Oncol Rep. 35:1227–1236. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Supic G, Kozomara R, Jovic N, Zeljic K and Magic Z: Hypermethylation of RUNX3 but not WIF1 gene and its association with stage and nodal status of tongue cancers. Oral Dis. 17:794–800. 2011. View Article : Google Scholar : PubMed/NCBI

24 

de Freitas Cordeiro-Silva M, Stur E, Agostini LP, de Podestá JR, de Oliveira JC, Soares MS, Mendonça EF, Gouvea SA, Von Zeidler SV and Louro ID: Promoter hypermethylation in primary squamous cell carcinoma of the oral cavity and oropharynx: A study of a Brazilian cohort. Mol Biol Rep. 39:10111–10119. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Zhang S, Feng XL, Shi L, Gong CJ, He ZJ, Wu HJ and Ling TY: Genome-wide analysis of DNA methylation in tongue squamous cell carcinoma. Oncol Rep. 29:1819–1826. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Hynes RO: Metastatic potential: Generic predisposition of the primary tumor or rare, metastatic variants-or both? Cell. 113:821–823. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Lambert AW, Pattabiraman DR and Weinberg RA: Emerging biological principles of metastasis. Cell. 168:670–691. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Hedbäck N, Jensen DH, Specht L, Fiehn AM, Therkildsen MH, Friis-Hansen L, Dabelsteen E and von Buchwald C: MiR-21 expression in the tumor stroma of oral squamous cell carcinoma: An independent biomarker of disease free survival. PLoS One. 9:e951932014. View Article : Google Scholar : PubMed/NCBI

29 

Shinriki S, Jono H, Ueda M, Obayashi K, Nakamura T, Ota K, Ota T, Sueyoshi T, Guo J, Hayashi M, et al: Stromal expression of neutrophil gelatinase-associated lipocalin correlates with poor differentiation and adverse prognosis in oral squamous cell carcinoma. Histopathology. 64:356–364. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Kudo Y, Tsunematsu T and Takata T: Oncogenic role of RUNX3 in head and neck cancer. J Cell Biochem. 112:387–393. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Tsunematsu T, Kudo Y, Iizuka S, Ogawa I, Fujita T, Kurihara H, Abiko Y and Takata T: RUNX3 has an oncogenic role in head and neck cancer. PLoS One. 4:e58922009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou WN, Du YF, Zheng Y, Zhang W, Wu YN, Song XM and Bai J: Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics. Mol Med Rep 19: 885-894, 2019.
APA
Zhou, W., Du, Y., Zheng, Y., Zhang, W., Wu, Y., Song, X., & Bai, J. (2019). Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics. Molecular Medicine Reports, 19, 885-894. https://doi.org/10.3892/mmr.2018.9705
MLA
Zhou, W., Du, Y., Zheng, Y., Zhang, W., Wu, Y., Song, X., Bai, J."Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics". Molecular Medicine Reports 19.2 (2019): 885-894.
Chicago
Zhou, W., Du, Y., Zheng, Y., Zhang, W., Wu, Y., Song, X., Bai, J."Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics". Molecular Medicine Reports 19, no. 2 (2019): 885-894. https://doi.org/10.3892/mmr.2018.9705
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou WN, Du YF, Zheng Y, Zhang W, Wu YN, Song XM and Bai J: Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics. Mol Med Rep 19: 885-894, 2019.
APA
Zhou, W., Du, Y., Zheng, Y., Zhang, W., Wu, Y., Song, X., & Bai, J. (2019). Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics. Molecular Medicine Reports, 19, 885-894. https://doi.org/10.3892/mmr.2018.9705
MLA
Zhou, W., Du, Y., Zheng, Y., Zhang, W., Wu, Y., Song, X., Bai, J."Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics". Molecular Medicine Reports 19.2 (2019): 885-894.
Chicago
Zhou, W., Du, Y., Zheng, Y., Zhang, W., Wu, Y., Song, X., Bai, J."Inactivation of RUNX3 protein expression in tongue squamous cell carcinoma and its association with clinicopathological characteristics". Molecular Medicine Reports 19, no. 2 (2019): 885-894. https://doi.org/10.3892/mmr.2018.9705
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