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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
May-2017 Volume 13 Issue 5

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
May-2017 Volume 13 Issue 5

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

MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase

  • Authors:
    • Weidong Xu
    • Huayong Jiang
    • Fuli Zhang
    • Junmao Gao
    • Jun Hou
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, The Military General Hospital of Beijing PLA, Beijing 100700, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3387-3394
    |
    Published online on: March 23, 2017
       https://doi.org/10.3892/ol.2017.5895
  • 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

Colorectal cancer (CRC) is the third most common cancer in males and the second most common in females, worldwide. Currently, 5-fluorouracil (5-FU)-mediated chemotherapy is the adjuvant treatment for patients with CRC following surgical resection. However, a number of patients with CRC develop 5‑FU resistance, which is a major challenge for the effective treatment of cancer. Therefore, it is important to investigate the molecular mechanisms underlying chemoresistance and the therapeutic treatments that may improve the treatment of CRC. The present study demonstrated that microRNA (miR)-330 was significantly downregulated in CRC tissues and cell lines. Ectopic miR‑330 expression decreased cell proliferation and enhanced cell chemosensitivity to 5‑FU via the cell apoptosis pathway in CRC. In addition, thymidylate synthase (TYMS) was revealed to be a direct target gene of miR‑330 in CRC. Knockdown of TYMS inhibited CRC cell proliferation, and enhanced cell chemosensitivity to 5‑FU by promoting cell apoptosis. In conclusion, the results of the present study indicated that miR‑330 targeted TYMS to inhibit the proliferation and enhance the chemosensitivity of CRC cells to 5-FU by promoting cell apoptosis. The present study provided important insight into the molecular mechanism underlying 5-FU-mediated chemoresistance and a novel therapeutic strategy for the enhancement of efficacy in CRC treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Andrews L: Dietary flavonoids for the prevention of colorectal cancer. Clin J Oncol Nurs. 17:671–672. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Altobelli E, Lattanzi A, Paduano R, Varassi G and di Orio F: Colorectal cancer prevention in Europe: Burden of disease and status of screening programs. Prev Med. 62:132–141. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Sugarbaker PH: Colorectal cancer: Prevention and management of metastatic disease. Biomed Res Int. 2014:7828902014. View Article : Google Scholar : PubMed/NCBI

6 

Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X, Jia W and Huang J: Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 6:2904–2911. 2013.PubMed/NCBI

7 

Sun Z, Zhou N, Han Q, Zhao L, Bai C, Chen Y, Zhou J and Zhao RC: MicroRNA-197 influences 5-fluorouracil resistance via thymidylate synthase in colorectal cancer. Clin Transl Oncol. 17:876–883. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Brouquet A and Nordlinger B: Metastatic colorectal cancer outcome and fatty liver disease. Nat Rev Gastroenterol Hepatol. 10:266–267. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Kuipers EJ, Rösch T and Bretthauer M: Colorectal cancer screening-optimizing current strategies and new directions. Nat Rev Clin Oncol. 10:130–142. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B and Starling N: Colorectal cancer. Lancet. 375:1030–1047. 2010. View Article : Google Scholar : PubMed/NCBI

12 

De Angelis PM, Svendsrud DH, Kravik KL and Stokke T: Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 5:202006. View Article : Google Scholar : PubMed/NCBI

13 

Zheng K, Liu W, Liu Y, Jiang C and Qian Q: MicroRNA-133a suppresses colorectal cancer cell invasion by targeting Fascin1. Oncol Lett. 9:869–874. 2015.PubMed/NCBI

14 

Yuan W, Sui C, Liu Q, Tang W, An H and Ma J: Up-regulation of microRNA-145 associates with lymph node metastasis in colorectal cancer. PLoS One. 9:e1020172014. View Article : Google Scholar : PubMed/NCBI

15 

Zhang Y, Wang Z, Chen M, Peng L, Wang X, Ma Q, Ma F and Jiang B: MicroRNA-143 targets MACC1 to inhibit cell invasion and migration in colorectal cancer. Mol Cancer. 11:232012. View Article : Google Scholar : PubMed/NCBI

16 

He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI

17 

O'Hara SP, Mott JL, Splinter PL, Gores GJ and LaRusso NF: MicroRNAs: Key modulators of posttranscriptional gene expression. Gastroenterology. 136:17–25. 2009. View Article : Google Scholar : PubMed/NCBI

18 

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

19 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Broderick JA and Zamore PD: MicroRNA therapeutics. Gene Ther. 18:1104–1110. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Lu F, Zhang J, Ji M, Li P, Du Y, Wang H, Zang S, Ma D, Sun X and Ji C: miR-181b increases drug sensitivity in acute myeloid leukemia via targeting HMGB1 and Mcl-1. Int J Oncol. 45:383–392. 2014.PubMed/NCBI

23 

Nagano H, Tomimaru Y, Eguchi H, Hama N, Wada H, Kawamoto K, Kobayashi S, Mori M and Doki Y: MicroRNA-29a induces resistance to gemcitabine through the Wnt/β-catenin signaling pathway in pancreatic cancer cells. Int J Oncol. 43:1066–1072. 2013.PubMed/NCBI

24 

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

25 

Thomas DM and Zalcberg JR: 5-fluorouracil: A pharmacological paradigm in the use of cytotoxics. Clin Exp Pharmacol Physiol. 25:887–895. 1998. View Article : Google Scholar : PubMed/NCBI

26 

Noordhuis P, Holwerda U, Van der Wilt CL, Van Groeningen CJ, Smid K, Meijer S, Pinedo HM and Peters GJ: 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers. Ann Oncol. 15:1025–1032. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Coget J, Borrini F, Susman S and Sabourin JC: Colorectal carcinomas in 2013: The search for powerful prognostic markers is still on the go! Cancer Biomark. 14:145–150. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Li T, Gao F and Zhang XP: miR-203 enhances chemosensitivity to 5-fluorouracil by targeting thymidylate synthase in colorectal cancer. Oncol Rep. 33:607–614. 2015.PubMed/NCBI

29 

Xu AG, Yu ZJ, Jiang B, Wang XY, Zhong XH, Liu JH, Lou QY and Gan AH: Colorectal cancer in Guangdong province of China: A demographic and anatomic survey. World J Gastroenterol. 16:960–965. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Ades S: Adjuvant chemotherapy for colon cancer in the elderly: Moving from evidence to practice. Oncology (Williston Park). 23:162–167. 2009.PubMed/NCBI

31 

McEwan DG, Brunton VG, Baillie GS, Leslie NR, Houslay MD and Frame MC: Chemoresistant KM12C colon cancer cells are addicted to low cyclic AMP levels in a phosphodiesterase 4-regulated compartment via effects on phosphoinositide 3-kinase. Cancer Res. 67:5248–5257. 2007. View Article : Google Scholar : PubMed/NCBI

32 

He Y, Wang J, Wang J, Yung VY, Hsu E, Li A, Kang Q, Ma J, Han Q, Jin P, et al: MicroRNA-135b regulates apoptosis and chemoresistance in colorectal cancer by targeting large tumor suppressor kinase 2. Am J Cancer Res. 5:1382–1395. 2015.PubMed/NCBI

33 

Mao Y, Chen H, Lin Y, Xu X, Hu Z, Zhu Y, Wu J, Xu X, Zheng X and Xie L: microRNA-330 inhibits cell motility by downregulating Sp1 in prostate cancer cells. Oncol Rep. 30:327–333. 2013.PubMed/NCBI

34 

Meng H, Wang K, Chen X, Guan X, Hu L, Xiong G, Li J and Bai Y: MicroRNA-330-3p functions as an oncogene in human esophageal cancer by targeting programmed cell death 4. Am J Cancer Res. 5:1062–1075. 2015.PubMed/NCBI

35 

Liu X, Shi H, Liu B, Li J, Liu Y and Yu B: miR-330-3p controls cell proliferation by targeting early growth response 2 in non-small-cell lung cancer. Acta Biochim Biophys Sin (Shanghai). 47:431–440. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Qu S, Yao Y, Shang C, Xue Y, Ma J, Li Z and Liu Y: MicroRNA-330 is an oncogenic factor in glioblastoma cells by regulating SH3GL2 gene. PLoS One. 7:e460102012. View Article : Google Scholar : PubMed/NCBI

37 

Heidelberger C, Chaudhuri NK, Danneberg P, Mooren D, Griesbach L, Duschinsky R, Schnitzer RJ, Pleven E and Scheiner J: Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 179:663–666. 1957. View Article : Google Scholar : PubMed/NCBI

38 

Liu Y, Du F, Zhao Q, Jin J, Ma X and Li H: Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells. Oncol Lett. 9:2675–2679. 2015.PubMed/NCBI

39 

Lehman NL: Future potential of thymidylate synthase inhibitors in cancer therapy. Expert Opin Investig Drugs. 11:1775–1787. 2002. View Article : Google Scholar : PubMed/NCBI

40 

Popat S, Matakidou A and Houlston RS: Thymidylate synthase expression and prognosis in colorectal cancer: A systematic review and meta-analysis. J Clin Oncol. 22:529–536. 2004. View Article : Google Scholar : PubMed/NCBI

41 

Lenz HJ, Hayashi K, Salonga D, Danenberg KD, Danenberg PV, Metzger R, Banerjee D, Bertino JR, Groshen S, Leichman LP and Leichman CG: p53 point mutations and thymidylate synthase messenger RNA levels in disseminated colorectal cancer: An analysis of response and survival. Clin Cancer Res. 4:1243–1250. 1998.PubMed/NCBI

42 

Copur S, Aiba K, Drake JC, Allegra CJ and Chu E: Thymidylate synthase gene amplification in human colon cancer cell lines resistant to 5-fluorouracil. Biochem Pharmacol. 49:1419–1426. 1995. View Article : Google Scholar : PubMed/NCBI

43 

Cho YB, Chung HJ, Lee WY, Choi SH, Kim HC, Yun SH and Chun HK: Relationship between TYMS and ERCC1 mRNA expression and in vitro chemosensitivity in colorectal cancer. Anticancer Res. 31:3843–3849. 2011.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xu W, Jiang H, Zhang F, Gao J and Hou J: MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase. Oncol Lett 13: 3387-3394, 2017.
APA
Xu, W., Jiang, H., Zhang, F., Gao, J., & Hou, J. (2017). MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase. Oncology Letters, 13, 3387-3394. https://doi.org/10.3892/ol.2017.5895
MLA
Xu, W., Jiang, H., Zhang, F., Gao, J., Hou, J."MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase". Oncology Letters 13.5 (2017): 3387-3394.
Chicago
Xu, W., Jiang, H., Zhang, F., Gao, J., Hou, J."MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase". Oncology Letters 13, no. 5 (2017): 3387-3394. https://doi.org/10.3892/ol.2017.5895
Copy and paste a formatted citation
x
Spandidos Publications style
Xu W, Jiang H, Zhang F, Gao J and Hou J: MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase. Oncol Lett 13: 3387-3394, 2017.
APA
Xu, W., Jiang, H., Zhang, F., Gao, J., & Hou, J. (2017). MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase. Oncology Letters, 13, 3387-3394. https://doi.org/10.3892/ol.2017.5895
MLA
Xu, W., Jiang, H., Zhang, F., Gao, J., Hou, J."MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase". Oncology Letters 13.5 (2017): 3387-3394.
Chicago
Xu, W., Jiang, H., Zhang, F., Gao, J., Hou, J."MicroRNA-330 inhibited cell proliferation and enhanced chemosensitivity to 5-fluorouracil in colorectal cancer by directly targeting thymidylate synthase". Oncology Letters 13, no. 5 (2017): 3387-3394. https://doi.org/10.3892/ol.2017.5895
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