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
September-2017 Volume 16 Issue 3

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
September-2017 Volume 16 Issue 3

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

Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221

  • Authors:
    • Liangzhi Du
    • Siwei Ma
    • Xi Wen
    • Juan Chai
    • Dangxia Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Implant Dentistry, Stomatology Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, School of Sports and Health, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China, Department of Oral and Maxillofacial Surgery and Stomatology, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China, Department of Pathology, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
    Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2659-2667
    |
    Published online on: July 4, 2017
       https://doi.org/10.3892/mmr.2017.6915
  • 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

Oral squamous cell carcinoma (OSCC) cells are usually resistant to doxorubicin, resulting in limited application of doxorubicin in OSCC treatment. MicroRNA (miR)‑221 has been reported to be involved in the development of OSCC; however, it remains unclear if and how miR‑221 is implicated in modulating the sensitivity of OSCC cells to doxorubicin. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to assess miR‑221 expression in OSCC cells in response to doxorubicin treatment. In addition, the SCC4 and SCC9 OSCC cell lines were transfected with anti‑miR‑221 oligonucleotides and cell viability and apoptosis following doxorubicin treatment were evaluated using an MTT assay and Annexin V‑fluorescein isothiocyanate/Hoechst double staining, respectively. The mRNA and protein expression levels of tissue inhibitor of metalloproteinase‑3 (TIMP3) in anti‑miR‑221‑transfected cells were assessed using RT‑qPCR and western blot analysis, respectively. Furthermore, a luciferase reporter assay was performed to investigate whether TIMP3 may be a direct target gene of miR‑221. To explore the roles of TIMP3 in miR‑221‑mediated cell responses, TIMP3 expression was silenced following transfection with TIMP3‑targeting small interfering (si)RNA in cells overexpressing miR‑221, and cell viability and apoptosis in response to doxorubicin treatment were measured. The results of the present study demonstrated that miR‑221 expression was upregulated in SCC4 and SCC9 cells following treatment with doxorubicin. However, inhibiting the doxorubicin‑induced upregulation of miR‑221 through transfection with anti‑miR‑221 oligonucleotides led to an increase in the sensitivity of OSCC cells to doxorubicin. In addition, the results indicated that TIMP3 was a direct target of miR‑221 in OSCC cells, as determined by a 3'‑untranslated region luciferase reporter assay. Co‑transfection of cells with anti‑miR‑221 oligonucleotides and TIMP3‑specific small interfering RNA resulted in reduced sensitivity to doxorubicin compared with the cells transfected with the miR‑221 inhibitor alone. In conclusion, these results indicated that OSCC cells are resistant to doxorubicin through upregulation of miR‑221, which in turn downregulates TIMP3. Therefore, silencing miR‑221 or upregulating TIMP3 may be considered promising therapeutic approaches to enhance the sensitivity of OSCC to doxorubicin.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancerbase No. 11 (Internet)International Agency for Research on Cancer. Lyon, France: 2013 http://globocan.iarc.frAccessed. May 19–2014

2 

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

3 

MacFarlane LA and Murphy PR: MicroRNA: Biogenesis, function and role in cancer. Curr Genomics. 11:537–561. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Garofalo M, Quintavalle C, Romano G, Croce CM and Condorelli G: miR221/222 in cancer: Their role in tumor progression and response to therapy. Curr Mol Med. 12:27–33. 2012. View Article : Google Scholar : PubMed/NCBI

5 

He S, Lai R, Chen D, Yan W, Zhang Z, Liu Z, Ding X and Chen Y: Downregulation of miR-221 inhibits cell migration and invasion through targeting methyl-CpG binding domain protein 2 in human oral squamous cell carcinoma cells. Biomed Res Int. 2015:7516722015. View Article : Google Scholar : PubMed/NCBI

6 

Nassirpour R, Mehta PP, Baxi SM and Yin MJ: miR-221 promotes tumorigenesis in human triple negative breast cancer cells. PLoS One. 8:e621702013. View Article : Google Scholar : PubMed/NCBI

7 

Wei Y, Lai X, Yu S, Chen S, Ma Y, Zhang Y, Li H, Zhu X, Yao L and Zhang J: Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells. Breast Cancer Res Treat. 147:423–431. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Zhao Y, Zhao L, Ischenko I, Bao Q, Schwarz B, Nieß H, Wang Y, Renner A, Mysliwietz J and Jauch KW: Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer. Target Oncol. 10:535–548. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Fornari F, Milazzo M, Galassi M, Callegari E, Veronese A, Miyaaki H, Sabbioni S, Mantovani V, Marasco E, Chieco P, et al: p53/mdm2 feedback loop sustains miR-221 expression and dictates the response to anticancer treatments in hepatocellular carcinoma. Mol Cancer Res. 12:203–216. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Yang CJ, Shen WG, Liu CJ, Chen YW, Lu HH, Tsai MM and Lin SC: miR-221 and miR-222 expression increased the growth and tumorigenesis of oral carcinoma cells. J Oral Pathol Med. 40:560–566. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Cruz-Munoz W and Khokha R: The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis. Crit Rev Clin Lab Sci. 45:291–338. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Gan R, Yang Y, Yang X, Zhao L, Lu J and Meng QH: Downregulation of miR-221/222 enhances sensitivity of breast cancer cells to tamoxifen through upregulation of TIMP3. Cancer Gene Ther. 21:290–296. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Garofalo M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, et al: miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 16:498–509. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Starr TK, Scott PM, Marsh BM, Zhao L, Than BL, O'Sullivan MG, Sarver AL, Dupuy AJ, Largaespada DA and Cormier RT: A sleeping beauty transposon-mediated screen identifies murine susceptibility genes for adenomatous polyposis coli (Apc)-dependent intestinal tumorigenesis. Proc Natl Acad Sci USA. 108:5765–5770. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Than BL, Goos JA, Sarver AL, O'Sullivan MG, Rod A, Starr TK, Fijneman RJ, Meijer GA, Zhao L, Zhang Y, et al: The role of KCNQ1 in mouse and human gastrointestinal cancers. Oncogene. 33:3861–3868. 2014. View Article : Google Scholar : PubMed/NCBI

16 

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

17 

Rong M, Chen G and Dang Y: Increased miR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro. BMC Cancer. 13:212013. View Article : Google Scholar : PubMed/NCBI

18 

Qiu D and Sun YC: Overexpression of miR-221 inhibits proliferation and promotes apoptosis of human astrocytoma cells. Int J Clin Exp Pathol. 8:4851–4856. 2015.PubMed/NCBI

19 

Tanaka T, Tanaka M and Tanaka T: Oral carcinogenesis and oral cancer chemoprevention: A review. Pathol Res Int. 2011:4312462011. View Article : Google Scholar

20 

Huang SH and O'Sullivan B: Oral cancer: Current role of radiotherapy and chemotherapy. Med Oral Patol Oral Cir Bucal. 18:e233–e240. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Gombos K, Horváth R, Szele E, Juhász K, Gocze K, Somlai K, Pajkos G, Ember I and Olasz L: miRNA expression profiles of oral squamous cell carcinomas. Anticancer Res. 33:1511–1517. 2013.PubMed/NCBI

22 

Das AM, Seynhaeve AL, Rens JA, Vermeulen CE, Koning GA, Eggermont AM and Ten Hagen TL: Differential TIMP3 expression affects tumor progression and angiogenesis in melanomas through regulation of directionally persistent endothelial cell migration. Angiogenesis. 17:163–177. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Du L, Ma S, Wen X, Chai J and Zhou D: Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221. Mol Med Rep 16: 2659-2667, 2017.
APA
Du, L., Ma, S., Wen, X., Chai, J., & Zhou, D. (2017). Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221. Molecular Medicine Reports, 16, 2659-2667. https://doi.org/10.3892/mmr.2017.6915
MLA
Du, L., Ma, S., Wen, X., Chai, J., Zhou, D."Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221". Molecular Medicine Reports 16.3 (2017): 2659-2667.
Chicago
Du, L., Ma, S., Wen, X., Chai, J., Zhou, D."Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221". Molecular Medicine Reports 16, no. 3 (2017): 2659-2667. https://doi.org/10.3892/mmr.2017.6915
Copy and paste a formatted citation
x
Spandidos Publications style
Du L, Ma S, Wen X, Chai J and Zhou D: Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221. Mol Med Rep 16: 2659-2667, 2017.
APA
Du, L., Ma, S., Wen, X., Chai, J., & Zhou, D. (2017). Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221. Molecular Medicine Reports, 16, 2659-2667. https://doi.org/10.3892/mmr.2017.6915
MLA
Du, L., Ma, S., Wen, X., Chai, J., Zhou, D."Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221". Molecular Medicine Reports 16.3 (2017): 2659-2667.
Chicago
Du, L., Ma, S., Wen, X., Chai, J., Zhou, D."Oral squamous cell carcinoma cells are resistant to doxorubicin through upregulation of miR‑221". Molecular Medicine Reports 16, no. 3 (2017): 2659-2667. https://doi.org/10.3892/mmr.2017.6915
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