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
December-2018 Volume 40 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-2018 Volume 40 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

Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2

  • Authors:
    • Junqing Chen
    • Wei Tian
    • Haifei He
    • Feng Chen
    • Jian Huang
    • Xiaojia Wang
    • Zhanhong Chen
  • View Affiliations / Copyright

    Affiliations: Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, Department of Breast Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Department of Breast Surgical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
  • Pages: 3821-3829
    |
    Published online on: September 26, 2018
       https://doi.org/10.3892/or.2018.6735
  • 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

Acquisition of resistance to paclitaxel is a major obstacle to successful treatment of breast cancer patients, but the molecular mechanisms underlying the development of drug resistance remain largely unclear. The aim of the present study was to investigate the role and mechanism of action of miR‑200c‑3p in the resistance of breast cancer to paclitaxel. It was observed that miR‑200c‑3p expression, as determined by reverse transcription‑quantitative polymerase chain reaction analysis, was significantly downregulated in paclitaxel‑resistant MCF‑7/Tax cells compared with parental MCF‑7 cells. Overexpression of miR‑200c‑3p increased the chemosensitivity to paclitaxel and enhanced apoptosis in MCF‑7/Tax cells, whereas the downregulation of miR‑200c‑3p exerted the opposite effect. In addition, upregulation of miR‑200c‑3p in MCF‑7/Tax cells suppressed the expression of sex‑determining region Y‑box 2 (SOX2) at the mRNA and protein levels. Dual‑luciferase reporter assay demonstrated that SOX2 is a target of miR‑200c‑3p in MCF‑7/Tax cells. Moreover, knockdown of SOX2 expression increased chemosensitivity to paclitaxel and upregulated miR‑200c‑3p expression in MCF‑7/Tax cells. Taken together, the results of the present study indicated that miR‑200c‑3p plays a key role in the development of paclitaxel resistance in breast cancer, possibly partially through regulating SOX2 expression, suggesting that the miR‑200c‑3p‑SOX2 loop may serve as a potential target for the reversal of paclitaxel resistance in breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Hassan MS, Ansari J, Spooner D and Hussain SA: Chemotherapy for breast cancer (Review). Oncol Rep. 24:1121–1131. 2010. View Article : Google Scholar : PubMed/NCBI

3 

O'Driscoll L and Clynes M: Biomarkers and multiple drug resistance in breast cancer. Curr Cancer Drug Targets. 6:365–384. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Ng EK, Wong CL, Ma ES and Kwong A: MicroRNAs as new players for diagnosis, prognosis, and therapeutic targets in breast cancer. J Oncol. 2009:3054202009. View Article : Google Scholar : PubMed/NCBI

5 

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

6 

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS and Johnson JM: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 433:769–773. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Amponsah PS, Fan P, Bauer N, Zhao Z, Gladkich J, Fellenberg J and Herr I: microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer. Cancer Lett. 388:107–117. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Ao X, Nie P, Wu B, Xu W, Zhang T, Wang S, Chang H and Zou Z: Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3. Cell Death Dis. 7:e24632016. View Article : Google Scholar : PubMed/NCBI

9 

Liu Y, Zhu ST, Wang X, Deng J, Li WH, Zhang P and Liu BS: MiR-200c regulates tumor growth and chemosensitivity to cisplatin in osteosarcoma by targeting AKT2. Sci Rep. 7:135982017. View Article : Google Scholar : PubMed/NCBI

10 

Cochrane DR, Howe EN, Spoelstra NS and Richer JK: Loss of miR-200c: A marker of aggressiveness and chemoresistance in female reproductive cancers. J Oncol. 2010:8217172010. View Article : Google Scholar : PubMed/NCBI

11 

Chen J, Tian W, Cai H, He H and Deng Y: Down-regulation of microRNA-200c is associated with drug resistance in human breast cancer. Med Oncol. 29:2527–2534. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Fong H, Hohenstein KA and Donovan PJ: Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells. Stem Cells. 26:1931–1938. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Leis O, Eguiara A, Lopez-Arribillaga E, Alberdi MJ, Hernandez-Garcia S, Elorriaga K, Pandiella A, Rezola R and Martin AG: Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 31:1354–1365. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Alonso MM, Diez-Valle R, Manterola L, Rubio A, Liu D, Cortes-Santiago N, Urquiza L, Jauregi P, de Munain Lopez A, Sampron N, et al: Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas. PLoS One. 6:e267402011. View Article : Google Scholar : PubMed/NCBI

15 

Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, Bergbower EA, Guan Y, Shin J, Guillory J, et al: Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 44:1111–1116. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Li D, Zhao LN, Zheng XL, Lin P, Lin F, Li Y, Zou HF, Cui RJ, Chen H and Yu XG: Sox2 is involved in paclitaxel resistance of the prostate cancer cell line PC-3 via the PI3K/Akt pathway. Mol Med Rep. 10:3169–3176. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Piva M, Domenici G, Iriondo O, Rábano M, Simões BM, Comaills V, Barredo I, López-Ruiz JA, Zabalza I, Kypta R and Vivanco MD: Sox2 promotes tamoxifen resistance in breast cancer cells. EMBO Mol Med. 6:66–79. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Wuebben EL, Wilder PJ, Cox JL, Grunkemeyer JA, Caffrey T, Hollingsworth MA and Rizzino A: SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells. Oncotarget. 7:34890–34906. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Mukherjee P, Gupta A, Chattopadhyay D and Chatterji U: Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells. Sci Rep. 7:91702017. View Article : Google Scholar : PubMed/NCBI

20 

Yang Q, Wang Y, Lu X, Zhao Z, Zhu L, Chen S, Wu Q, Chen C and Wang Z: MiR-125b regulates epithelial-mesenchymal transition via targeting Sema4C in paclitaxel-resistant breast cancer cells. Oncotarget. 6:3268–3279. 2015.PubMed/NCBI

21 

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

22 

Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI and Kovalchuk O: Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer. 127:1785–1794. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Zhu W, Xu H, Zhu D, Zhi H, Wang T, Wang J, Jiang B, Shu Y and Liu P: miR-200bc/429 cluster modulates multidrug resistance of human cancer cell lines by targeting BCL2 and XIAP. Cancer Chemother Pharmacol. 69:723–731. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Moon JH, Nakajima K, Takiguchi S, Fujiwara Y, Mori M and Doki Y: Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the Akt signaling pathway. Clin Cancer Res. 17:3029–3038. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, et al: Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 138:592–603. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Gao C, Peng FH and Peng LK: MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1. Neoplasma. 61:680–689. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Park SM, Gaur AB, Lengyel E and Peter ME: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22:894–907. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Korpal M, Lee ES, Hu G and Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 283:14910–14914. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Brabletz S and Brabletz T: The ZEB/miR-200 feedback loop-a motor of cellular plasticity in development and cancer. EMBO Rep. 11:670–677. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Hill L, Browne G and Tulchinsky E: ZEB/miR-200 feedback loop: At the crossroads of signal transduction in cancer. Int J Cancer. 132:745–754. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Peng C, Li N, Ng YK, Zhang J, Meier F, Theis FJ, Merkenschlager M, Chen W, Wurst W and Prakash N: A unilateral negative feedback loop between miR-200 microRNAs and Sox2/E2F3 controls neural progenitor cell-cycle exit and differentiation. J Neurosci. 32:13292–13308. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Lu YX, Yuan L, Xue XL, Zhou M, Liu Y, Zhang C, Li JP, Zheng L, Hong M and Li XN: Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR-200c-Sox2-negative feedback loop mechanism. Clin Cancer Res. 20:2631–2642. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen J, Tian W, He H, Chen F, Huang J, Wang X and Chen Z: Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. Oncol Rep 40: 3821-3829, 2018.
APA
Chen, J., Tian, W., He, H., Chen, F., Huang, J., Wang, X., & Chen, Z. (2018). Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. Oncology Reports, 40, 3821-3829. https://doi.org/10.3892/or.2018.6735
MLA
Chen, J., Tian, W., He, H., Chen, F., Huang, J., Wang, X., Chen, Z."Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2". Oncology Reports 40.6 (2018): 3821-3829.
Chicago
Chen, J., Tian, W., He, H., Chen, F., Huang, J., Wang, X., Chen, Z."Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2". Oncology Reports 40, no. 6 (2018): 3821-3829. https://doi.org/10.3892/or.2018.6735
Copy and paste a formatted citation
x
Spandidos Publications style
Chen J, Tian W, He H, Chen F, Huang J, Wang X and Chen Z: Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. Oncol Rep 40: 3821-3829, 2018.
APA
Chen, J., Tian, W., He, H., Chen, F., Huang, J., Wang, X., & Chen, Z. (2018). Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2. Oncology Reports, 40, 3821-3829. https://doi.org/10.3892/or.2018.6735
MLA
Chen, J., Tian, W., He, H., Chen, F., Huang, J., Wang, X., Chen, Z."Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2". Oncology Reports 40.6 (2018): 3821-3829.
Chicago
Chen, J., Tian, W., He, H., Chen, F., Huang, J., Wang, X., Chen, Z."Downregulation of miR‑200c‑3p contributes to the resistance of breast cancer cells to paclitaxel by targeting SOX2". Oncology Reports 40, no. 6 (2018): 3821-3829. https://doi.org/10.3892/or.2018.6735
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