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
May-2018 Volume 17 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-2018 Volume 17 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

Downregulation of human choline kinase α gene expression by miR-876-5p

  • Authors:
    • Sharzehan Mohamad Ayub Khan
    • Ling Ling Few
    • Wei Cun See Too
  • View Affiliations / Copyright

    Affiliations: School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia, School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
  • Pages: 7442-7450
    |
    Published online on: March 16, 2018
       https://doi.org/10.3892/mmr.2018.8762
  • 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

Choline kinase (CK) is the first enzyme in the CDP-choline pathway for the synthesis of phosphatidylcholine, the most abundant phospholipid in the mammalian cell membrane. This enzyme exists as three isozymes (α1, α2 and β) and the CKα isozyme has been implicated in cancer pathogenesis. Inhibition of CK activity has been proposed for cancer therapies. MicroRNAs (miRNAs/miRs) are non‑coding RNAs that serve important roles in diverse biological pathways and human diseases, including cancer. However, the regulation of CKα gene expression by miRNAs has never been investigated, to the best of the authors' knowledge. In the present study, two miRNA mimics, miR‑876‑5p and miR‑646, were transfected into the HepG2 cell line and the effect of these miRNAs on the levels of CKα mRNA were determined by reverse transcription‑quantitative polymerase chain reaction. Cells transfected with 25 nM miR‑876‑5p for 48 h exhibited significantly lower levels of CKα mRNA. Following optimization, miR‑876‑5p caused four times lower levels of CKα mRNA compared to the negative control. Effects of the miRNAs on HepG2 cell viability and cellular morphology were additionally analyzed using an MTT cell viability assay and scanning electron microscopy, respectively. HepG2 cells that were transfected with the optimum concentration of miR‑876‑5p for the optimum duration exhibited 25% lower viability than negative control and signs of apoptosis in electron micrographs. The results suggested miR‑876‑5p as a potential miRNA modulator of CKα expression in the cells, and may be relevant for the design of more effective anticancer strategy targeting CK.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Lykidis A, Wang J, Karim MA and Jackowski S: Overexpression of a mammalian ethanolamine-specific kinase accelerates the CDP-ethanolamine pathway. J Biol Chem. 276:2174–2179. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Malito E, Sekulic N, Too WC, Konrad M and Lavie A: Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine. J Mol Biol. 364:136–151. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Aoyama C, Ohtani A and Ishidate K: Expression and characterization of the active molecular forms of choline/ethanolamine kinase-alpha and -beta in mouse tissues, including carbon tetrachloride-induced liver. Biochem J. 363:777–784. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Gallego-Ortega D, Ramirez de Molina A, Ramos MA, Valdes-Mora F, Barderas MG, Sarmentero-Estrada J and Lacal JC: Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: Implications in cancer onset and treatment. PLoS One. 4:e78192009. View Article : Google Scholar : PubMed/NCBI

5 

Ramírez de Molina A, Gutiérrez R, Ramos MA, Silva JM, Silva J, Bonilla F, Sánchez JJ and Lacal JC: Increased choline kinase activity in human breast carcinomas: Clinical evidence for a potential novel antitumor strategy. Oncogene. 21:4317–4322. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Nakagami K, Uchida T, Ohwada S, Koibuchi Y, Suda Y, Sekine T and Morishita Y: Increased choline kinase activity and elevated phosphocholine levels in human colon cancer. Jpn J Cancer Res. 90:419–424. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Ramírez de Molina A, Rodríguez-González A, Gutiérrez R, Martínez-Piñeiro L, Sánchez J, Bonilla F, Rosell R and Lacal J: Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun. 296:580–583. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Shah T, Wildes F, Penet MF, Winnard PT Jr, Glunde K, Artemov D, Ackerstaff E, Gimi B, Kakkad S, Raman V and Bhujwalla ZM: Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells. NMR Biomed. 23:633–642. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Rodríguez-González A, Ramirez de Molina A, Fernández F and Lacal JC: Choline kinase inhibition induces the increase in ceramides resulting in a highly specific and selective cytotoxic antitumoral strategy as a potential mechanism of action. Oncogene. 23:8247–8259. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Bañez-Coronel M, Ramírez de Molina A, Rodríguez-González A, Sarmentero J, Ramos MA, García-Cabezas MA, García-Oroz L and Lacal JC: Choline kinase alpha depletion selectively kills tumoral cells. Curr Cancer Drug Targets. 8:709–719. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Gruber J, See Too WC, Wong MT, Lavie A, McSorley T and Konrad M: Balance of human choline kinase isoforms is critical for cell cycle regulation: Implications for the development of choline kinase-targeted cancer therapy. FEBS J. 279:1915–1928. 2012. View Article : Google Scholar : PubMed/NCBI

12 

MacKeigan JP, Murphy LO and Blenis J: Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. Nat Cell Biol. 7:591–600. 2005. View Article : Google Scholar : PubMed/NCBI

13 

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

14 

Almeida MI, Reis RM and Calin GA: MicroRNA history: Discovery, recent applications, and next frontiers. Mutat Res. 717:1–8. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Vella MC and Slack FJ: C. elegans microRNAs. WormBook. 1–9. 2005.PubMed/NCBI

17 

Williams AH, Liu N, van Rooij E and Olson EN: MicroRNA control of muscle development and disease. Curr Opin Cell Biol. 21:461–469. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 94:776–780. 2006. View Article : Google Scholar : PubMed/NCBI

19 

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

20 

Stenvang J, Petri A, Lindow M, Obad S and Kauppinen S: Inhibition of microRNA function by antimiR oligonucleotides. Silence. 3:12012. View Article : Google Scholar : PubMed/NCBI

21 

Conde J, Oliva N, Atilano M, Song HS and Artzi N: Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment. Nat Mater. 15:353–363. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Jansson MD and Lund AH: MicroRNA and cancer. Mol Oncol. 6:590–610. 2012. View Article : Google Scholar : PubMed/NCBI

23 

López-Terrada D, Cheung SW, Finegold MJ and Knowles BB: Hep G2 is a hepatoblastoma-derived cell line. Hum Pathol. 40:1512–1515. 2009. View Article : Google Scholar

24 

Brennecke J, Stark A, Russell RB and Cohen SM: Principles of microRNA-target recognition. PLoS Biol. 3:e852005. View Article : Google Scholar : PubMed/NCBI

25 

Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP and Bartel DP: MicroRNA targeting specificity in mammals: Determinants beyond seed pairing. Mol Cell. 27:91–105. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Chua SL, See Too WC, Khoo BY and Few LL: UBC and YWHAZ as suitable reference genes for accurate normalisation of gene expression using MCF7, HCT116 and HepG2 cell lines. Cytotechnology. 63:645–654. 2011. View Article : Google Scholar : PubMed/NCBI

28 

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

29 

McDowell EM and Trump BF: Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med. 100:405–414. 1976.PubMed/NCBI

30 

Bandres E, Agirre X, Ramirez N, Zarate R and Garcia-Foncillas J: MicroRNAs as cancer players: Potential clinical and biological effects. DNA Cell Biol. 26:273–282. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Peterson SM, Thompson JA, Ufkin ML, Sathyanarayana P, Liaw L and Congdon CB: Common features of microRNA target prediction tools. Front Genet. 5:232014. View Article : Google Scholar : PubMed/NCBI

32 

Wang RY, Weng KF, Huang YC and Chen CJ: Elevated expression of circulating miR876-5p is a specific response to severe EV71 infections. Sci Rep. 6:241492016. View Article : Google Scholar : PubMed/NCBI

33 

Cook JR, MacIntyre DA, Samara E, Kim SH, Singh N, Johnson MR, Bennett PR and Terzidou V: Exogenous oxytocin modulates human myometrial microRNAs. Am J Obstet Gynecol. 213:65.e1–e9. 2015. View Article : Google Scholar

34 

Saiselet M, Gacquer D, Spinette A, Craciun L, Decaussin-Petrucci M, Andry G, Detours V and Maenhaut C: New global analysis of the microRNA transcriptome of primary tumors and lymph node metastases of papillary thyroid cancer. BMC Genomics. 16:8282015. View Article : Google Scholar : PubMed/NCBI

35 

Liu X, Gao Y, Lu Y, Zhang J, Li L and Yin F: Downregulation of NEK11 is associated with drug resistance in ovarian cancer. Int J Oncol. 45:1266–1274. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Huang YH, Lin KH, Chen HC, Chang ML, Hsu CW, Lai MW, Chen TC, Lee WC, Tseng YH and Yeh CT: Identification of postoperative prognostic microRNA predictors in hepatocellular carcinoma. PLoS One. 7:e371882012. View Article : Google Scholar : PubMed/NCBI

37 

Sun XH, Geng XL, Zhang J and Zhang C: miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2). Tumour Biol. 36:2127–2134. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Azam AT, Bahador R, Hesarikia H, Shakeri M and Yeganeh A: Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression, metastasis, and unfavorable prognosis of human osteosarcoma. Tumour Biol. 37:5769–5773. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Li Z, Wu G, Sher RB, Khavandgar Z, Hermansson M, Cox GA, Doschak MR, Murshed M, Beier F and Vance DE: Choline kinase beta is required for normal endochondral bone formation. Biochim Biophys Acta. 1840:2112–2122. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Bollin F, Dechavanne V and Chevalet L: Design of experiment in CHO and HEK transient transfection condition optimization. Protein Expr Purif. 78:61–68. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Borawski J, Lindeman A, Buxton F, Labow M and Gaither LA: Optimization procedure for small interfering RNA transfection in a 384-well format. J Biomol Screen. 12:546–559. 2007. View Article : Google Scholar : PubMed/NCBI

42 

Jin HY, Gonzalez-Martin A, Miletic AV, Lai M, Knight S, Sabouri-Ghomi M, Head SR, Macauley MS, Rickert RC and Xiao C: Transfection of microRNA mimics should be used with caution. Front Genet. 6:3402015. View Article : Google Scholar : PubMed/NCBI

43 

Hengstermann A, D'Silva MA, Kuballa P, Butz K, Hoppe-Seyler F and Scheffner M: Growth suppression induced by downregulation of E6-AP expression in human papillomavirus-positive cancer cell lines depends on p53. J Virol. 79:9296–9300. 2005. View Article : Google Scholar : PubMed/NCBI

44 

Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA and van Oudenaarden A: MicroRNAs can generate thresholds in target gene expression. Nat Genet. 43:854–859. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ayub Khan SM, Few LL and See Too WC: Downregulation of human choline kinase α gene expression by miR-876-5p. Mol Med Rep 17: 7442-7450, 2018.
APA
Ayub Khan, S.M., Few, L.L., & See Too, W.C. (2018). Downregulation of human choline kinase α gene expression by miR-876-5p. Molecular Medicine Reports, 17, 7442-7450. https://doi.org/10.3892/mmr.2018.8762
MLA
Ayub Khan, S. M., Few, L. L., See Too, W. C."Downregulation of human choline kinase α gene expression by miR-876-5p". Molecular Medicine Reports 17.5 (2018): 7442-7450.
Chicago
Ayub Khan, S. M., Few, L. L., See Too, W. C."Downregulation of human choline kinase α gene expression by miR-876-5p". Molecular Medicine Reports 17, no. 5 (2018): 7442-7450. https://doi.org/10.3892/mmr.2018.8762
Copy and paste a formatted citation
x
Spandidos Publications style
Ayub Khan SM, Few LL and See Too WC: Downregulation of human choline kinase α gene expression by miR-876-5p. Mol Med Rep 17: 7442-7450, 2018.
APA
Ayub Khan, S.M., Few, L.L., & See Too, W.C. (2018). Downregulation of human choline kinase α gene expression by miR-876-5p. Molecular Medicine Reports, 17, 7442-7450. https://doi.org/10.3892/mmr.2018.8762
MLA
Ayub Khan, S. M., Few, L. L., See Too, W. C."Downregulation of human choline kinase α gene expression by miR-876-5p". Molecular Medicine Reports 17.5 (2018): 7442-7450.
Chicago
Ayub Khan, S. M., Few, L. L., See Too, W. C."Downregulation of human choline kinase α gene expression by miR-876-5p". Molecular Medicine Reports 17, no. 5 (2018): 7442-7450. https://doi.org/10.3892/mmr.2018.8762
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