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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December-2020 Volume 46 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-2020 Volume 46 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
Article Open Access

Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway

  • Authors:
    • Jin Feng
    • Zhong Li
    • Ling Li
    • Haibin Xie
    • Qicheng Lu
    • Xiaozhou He
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213029, P.R. China, Department of Urology Surgery, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213029, P.R. China
    Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1973-1982
    |
    Published online on: October 7, 2020
       https://doi.org/10.3892/ijmm.2020.4747
  • 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

Circular RNAs (circRNAs) have been reported to be involved in the progression of colorectal cancer (CRC). However, the biological role of circCCDC66 in CRC remains unclear. Therefore, the present study aimed to elucidate the mechanisms through which circCCDC66 affects the hypoxia‑induced progression of CRC. It was found that hypoxia promoted the progression of CRC and upregulated the expression of circCCDC66. Furthermore, circCCDC66‑knockdown reduced viability, migration and invasion, and enhanced the apoptosis of hypoxia‑exposed CRC cells. Using the starBase database, it was identified that circCCDC66 may bind to miR‑3140. Subsequently, it was confirmed that circCCDC66 serves as a sponge of miR‑3140 and the depletion of miR‑3140 partly abolished the effects of circCCDC66 on the phenotype of hypoxia‑exposed CRC cells. In addition, miR‑3140 was validated to inhibit the autophagy pathway. The use of an autophagy inducer partially reversed the miR‑3140 overexpression‑induced inhibition of the viability and invasion, and the promotion of the apoptosis of hypoxia‑exposed CRC cells. In summary, the findings of the present study demonstrated that circCCDC66 facilitates the development of CRC cells under hypoxic conditions via regulation of miR‑3140/autophagy. These findings may provide a novel therapeutic option for patients with CRC.
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, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Brenner H, Kloor M and Pox CP: Colorectal cancer. Lancet. 383:1490–1502. 2014. View Article : Google Scholar

3 

Bruera G and Ricevuto E: Intensive chemotherapy of metastatic colorectal cancer: Weighing between safety and clinical efficacy: Evaluation of Masi G, Loupakis F, Salvatore L, et al: Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: A phase 2 trial. Lancet Oncol. 11:845–852. 2010. View Article : Google Scholar

Expert Opin Biol Ther. 11:821–814. 2011. View Article : Google Scholar

4 

Petrelli F and Barni S: Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer. Ann Oncol. 24:186–192. 2013. View Article : Google Scholar

5 

Zheng H, Wu Y, Guo T, Liu F, Xu Y and Cai S: Hypoxia induces growth differentiation factor 15 to promote the metastasis of colorectal cancer via PERK-eIF2α signaling. Biomed Res Int. 2020:59582722020. View Article : Google Scholar

6 

Choi BJ, Park SA, Lee SY, Cha YN and Surh YJ: Hypoxia induces epithelial-mesenchymal transition in colorectal cancer cells through ubiquitin-specific protease 47-mediated stabilization of Snail: A potential role of Sox9. Sci Rep. 7:159182017. View Article : Google Scholar : PubMed/NCBI

7 

Guo JU, Agarwal V, Guo H and Bartel DP: Expanded identification and characterization of mammalian circular RNAs. Genome Biol. 15:4092014. View Article : Google Scholar : PubMed/NCBI

8 

Barrett SP, Wang PL and Salzman J: Circular RNA biogenesis can proceed through an exon-containing lariat precursor. Elife. 4:e075402015. View Article : Google Scholar : PubMed/NCBI

9 

Liang H, Huang H, Li Y, Lu Y and Ye T: CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis. Biosci Rep. 40:BSR201934842020. View Article : Google Scholar : PubMed/NCBI

10 

Hu K, Qin X, Shao Y, Zhou Y, Ye G and Xu S: Circular RNA MTO1 suppresses tumorigenesis of gastric carcinoma by sponging miR-200-5p and targeting PEBP1. Mol Cell Probes. 52:1015622020. View Article : Google Scholar

11 

Bian L, Zhi X, Ma L, Zhang J, Chen P, Sun S, Li J, Sun Y and Qin J: Hsa_circRNA_103809 regulated the cell proliferation and migration in colorectal cancer via miR-532-3p/FOXO4 axis. Biochem Biophys Res Commun. 505:346–352. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Zeng K, Chen X, Xu M, Liu X, Hu X, Xu T, Sun H, Pan Y, He B and Wang S: CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7. Cell Death Dis. 9:4172018. View Article : Google Scholar : PubMed/NCBI

13 

Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS and Tsai SJ: Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res. 77:2339–2350. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Wei Y, Zhang Y, Meng Q, Cui L and Xu C: Hypoxia-induced circular RNA has_circRNA_403658 promotes bladder cancer cell growth through activation of LDHA. Am J Transl Res. 11:6838–6849. 2019.PubMed/NCBI

15 

Ren S, Liu J, Feng Y, Li Z, He L, Li L, Cao X, Wang Z and Zhang Y: Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia. J Exp Clin Cancer Res. 38:3882019. View Article : Google Scholar : PubMed/NCBI

16 

Turchinovich A, Weiz L and Burwinkel B: Extracellular miRNAs: The mystery of their origin and function. Trends Biochem Sci. 37:460–465. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, Winnay JN, Garcia-Martin R, Grinspoon SK, et al: Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 542:450–455. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Sun N, Zhang L, Zhang C and Yuan Y: miR-144-3p inhibits cell proliferation of colorectal cancer cells by targeting BCL6 via inhibition of Wnt/β-catenin signaling. Cell Mol Biol Lett. 25:192020. View Article : Google Scholar

19 

Weihua Z, Guorong Z, Xiaolong C and Weizhan L: MiR-33a functions as a tumor suppressor in triple-negative breast cancer by targeting EZH2. Cancer Cell Int. 20:852020. View Article : Google Scholar : PubMed/NCBI

20 

Fang QY, Deng QF, Luo J and Zhou CC: MiRNA-20a-5p accelerates the proliferation and invasion of non-small cell lung cancer by targeting and downregulating KLF9. Eur Rev Med Pharmacol Sci. 24:2548–2556. 2020.PubMed/NCBI

21 

Tonouchi E, Gen Y, Muramatsu T, Hiramoto H, Tanimoto K, Inoue J and Inazawa J: miR-3140 suppresses tumor cell growth by targeting BRD4 via its coding sequence and downregulates the BRD4-NUT fusion oncoprotein. Sci Rep. 8:44822018. View Article : Google Scholar : PubMed/NCBI

22 

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

23 

Dong Y, He D, Peng Z, Peng W, Shi W, Wang J, Li B, Zhang C and Duan C: Circular RNAs in cancer: An emerging key player. J Hematol Oncol. 10:22017. View Article : Google Scholar : PubMed/NCBI

24 

Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P and Wu M: CircRNA: Functions and properties of a novel potential biomarker for cancer. Mol Cancer. 16:942017. View Article : Google Scholar : PubMed/NCBI

25 

Luan W, Shi Y, Zhou Z, Xia Y and Wang J: CircRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis. Biochem Biophys Res Commun. 502:22–29. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Li H, Jin X, Liu B, Zhang P, Chen W and Li Q: CircRNA CBL.11 suppresses cell proliferation by sponging miR-6778-5p in colorectal cancer. BMC Cancer. 19:8262019. View Article : Google Scholar : PubMed/NCBI

27 

Kim CW, Oh ET, Kim JM, Park JS, Lee DH, Lee JS, Kim KK and Park HJ: Hypoxia-induced microRNA-590-5p promotes colorectal cancer progression by modulating matrix metalloproteinase activity. Cancer Lett. 416:31–41. 2018. View Article : Google Scholar

28 

Ullmann P, Nurmik M, Schmitz M, Rodriguez F, Weiler J, Qureshi-Baig K, Felten P, Nazarov PV, Nicot N, Zuegel N, et al: Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity. Cancer Lett. 450:32–41. 2019. View Article : Google Scholar : PubMed/NCBI

29 

Zhang L, Song X, Chen X, Wang Q, Zheng X, Wu C and Jiang J: Circular RNA CircCACTIN promotes gastric cancer progression by sponging MiR-331-3p and regulating TGFBR1 expression. Int J Biol Sci. 15:1091–1103. 2019. View Article : Google Scholar : PubMed/NCBI

30 

Wei S, Zheng Y, Jiang Y, Li X, Geng J, Shen Y, Li Q, Wang X, Zhao C, Chen Y, et al: The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p. EBioMedicine. 44:182–193. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J and Califano A: An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 147:370–381. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Tu FL, Guo XQ, Wu HX, He ZY, Wang F, Sun AJ and Dai XD: Circ-0001313/miRNA-510-5p/AKT2 axis promotes the development and progression of colon cancer. Am J Transl Res. 12:281–291. 2020.PubMed/NCBI

34 

He JH, Han ZP, Luo JG, Jiang JW, Zhou JB, Chen WM, Lv YB, He ML, Zheng L, Li YG and Zuo JD: Hsa_Circ_0007843 acts as a mIR-518c-5p sponge to regulate the migration and invasion of colon cancer SW480 cells. Front Genet. 11:92020. View Article : Google Scholar : PubMed/NCBI

35 

Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B and Bao JK: Programmed cell death pathways in cancer: A review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 45:487–498. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Qureshi-Baig K, Kuhn D, Viry E, Pozdeev VI, Schmitz M, Rodriguez F, Ullmann P, Koncina E, Nurmik M, Frasquilho S, et al: Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway. Autophagy. Jan 17–2019.Epub ahead of print. PubMed/NCBI

37 

Che J, Wang W, Huang Y, Zhang L, Zhao J, Zhang P and Yuan X: miR-20a inhibits hypoxia-induced autophagy by targeting ATG5/FIP200 in colorectal cancer. Mol Carcinog. 58:1234–1247. 2019.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Feng J, Li Z, Li L, Xie H, Lu Q and He X: Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway. Int J Mol Med 46: 1973-1982, 2020.
APA
Feng, J., Li, Z., Li, L., Xie, H., Lu, Q., & He, X. (2020). Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway. International Journal of Molecular Medicine, 46, 1973-1982. https://doi.org/10.3892/ijmm.2020.4747
MLA
Feng, J., Li, Z., Li, L., Xie, H., Lu, Q., He, X."Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway". International Journal of Molecular Medicine 46.6 (2020): 1973-1982.
Chicago
Feng, J., Li, Z., Li, L., Xie, H., Lu, Q., He, X."Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway". International Journal of Molecular Medicine 46, no. 6 (2020): 1973-1982. https://doi.org/10.3892/ijmm.2020.4747
Copy and paste a formatted citation
x
Spandidos Publications style
Feng J, Li Z, Li L, Xie H, Lu Q and He X: Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway. Int J Mol Med 46: 1973-1982, 2020.
APA
Feng, J., Li, Z., Li, L., Xie, H., Lu, Q., & He, X. (2020). Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway. International Journal of Molecular Medicine, 46, 1973-1982. https://doi.org/10.3892/ijmm.2020.4747
MLA
Feng, J., Li, Z., Li, L., Xie, H., Lu, Q., He, X."Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway". International Journal of Molecular Medicine 46.6 (2020): 1973-1982.
Chicago
Feng, J., Li, Z., Li, L., Xie, H., Lu, Q., He, X."Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway". International Journal of Molecular Medicine 46, no. 6 (2020): 1973-1982. https://doi.org/10.3892/ijmm.2020.4747
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