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 and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
January-2020 Volume 12 Issue 1

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
January-2020 Volume 12 Issue 1

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

Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes

  • Authors:
    • Houguang Liu
    • Zheng Li
    • Shanshan Huo
    • Qiongling Wei
    • Ling Ge
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, The Third Hospital of Xiamen, Xiamen, Fujian 361100, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 9-14
    |
    Published online on: November 20, 2019
       https://doi.org/10.3892/mco.2019.1952
  • 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

Cutaneous melanoma is one of the most common malignant skin tumors, with a continuously increasing incidence. Cyclin‑dependent kinase (CDK) 2 is a key regulator of G1‑S transition and modulation of G2 progression; however, its role in cancer is a matter of debate. In the present study, a lentivirus expressing single‑guide RNA (sgRNA) was constructed to knock out CDK2 using CRISP/Cas9 technology, in order to confirm the role of CDK2 in A375 human melanoma cells. The results demonstrated that CDK2 knockout induced G0/G1 phase arrest and early apoptosis by downregulating the expression of CDK4 and cyclin A2, and by upregulating the expression of cyclin D1. These results suggest that therapeutic strategies designed to target CDK2 using CRISP/Cas9 may improve the treatment outcome of cutaneous melanoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Little EG and Eide MJ: Update on the current state of melanoma incidence. Dermatol Clin. 30:355–361. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Quintanilla-Dieck MJ and Bichakjian CK: Management of early-stage melanoma. Facial Plast Surg Clin North Am. 27:35–42. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Guy GP Jr, Thomas CC, Thompson T, Watson M, Massetti GM and Richardson LC; Centers for Disease Control and Prevention (CDC), : Vital signs: Melanoma incidence and mortality trends and projections-United States, 1982–2030. MMWR Morb Mortal Wkly Rep. 64:591–596. 2015.PubMed/NCBI

4 

Duffy KL, Truong A, Bowen GM, Andtbacka RH, Hyngstrom J, Bowles T, Grossmann K, Khong H, Hyde M, Florell SR, et al: Adequacy of 5-mm surgical excision margins for non-lentiginous melanoma in situ. J Am Acad Dermatol. 71:835–838. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Nadiminti H, Scope A, Marghoob AA, Busam K and Nehal KS: Use of reflectance confocal microscopy to monitor response of lentigo maligna to nonsurgical treatment. Dermatol Surg. 36:177–184. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Nurse P, Masui Y and Hartwell L: Understanding the cell cycle. Nat Med. 4:1103–1106. 1998. View Article : Google Scholar : PubMed/NCBI

7 

Hunt T, Nasmyth K and Novák B: The cell cycle. Philos Trans R Soc Lond B Biol Sci. 366:3494–3497. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Malumbres M: Physiological relevance of cell cycle kinases. Physiol Rev. 91:973–1007. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Hunt T: Nobel Lecture. Protein synthesis, proteolysis, and cell cycle transitions. Biosci Rep. 22:465–486. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Merrick KA, Wohlbold L, Zhang C, Allen JJ, Horiuchi D, Huskey NE, Goga A, Shokat KM and Fisher RP: Switching Cdk2 on or off with small molecules to reveal requirements in human cell proliferation. Mol Cell. 42:624–636. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Guadagno TM and Newport JW: Cdk2 kinase is required for entry into mitosis as a positive regulator of Cdc2-cyclin B kinase activity. Cell. 84:73–82. 1996. View Article : Google Scholar : PubMed/NCBI

12 

McCurdy SR, Pacal M, Ahmad M and Bremner R: A CDK2 activity signature predicts outcome in CDK2-low cancers. Oncogene. 36:2491–2502. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Chohan TA, Qian H, Pan Y and Chen JZ: Cyclin-dependent kinase-2 as a target for cancer therapy: Progress in the development of CDK2 inhibitors as anti-cancer agents. Curr Med Chem. 22:237–263. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Tetsu O and McCormick F: Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell. 3:233–245. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Hochegger H, Dejsuphong D, Sonoda E, Saberi A, Rajendra E, Kirk J, Hunt T and Takeda S: An essential role for Cdk1 in S phase control is revealed via chemical genetics in vertebrate cells. J Cell Biol. 178:257–268. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Berthet C, Aleem E, Coppola V, Tessarollo L and Kaldis P: Cdk2 knockout mice are viable. Curr Biol. 13:1775–1785. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Enders GH: Mammalian interphase cdks: Dispensable master regulators of the cell cycle. Genes Cancer. 3:614–618. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Adelmann CH, Wang T, Sabatini DM and Lander ES: Genome-wide CRISPR/Cas9 screening for identification of cancer genes in cell lines. Methods Mol Biol. 1907:125–136. 2019. View Article : Google Scholar : PubMed/NCBI

19 

Slipek NJ, Varshney J and Largaespada DA: CRISPR/Cas9-based positive screens for cancer-related traits. Methods Mol Biol. 1907:137–144. 2019. View Article : Google Scholar : PubMed/NCBI

20 

Liu HG, Liu Z, Jiang Y, Xiao JR, Li HY, Li Z, Huo SS and Yu YJ: Apoptosis of human melanoma A375 cells induced by lentivirus mediated CDK2-shRNA. Chin J Gerontol. 35:6345–6347. 2015.(In Chinese).

21 

Liu HG, Liu Z, Jiang Y, Xiao JR, Li HY, Li Z, Huo SS and Yu YJ: Apoptosis of human melanoma A375 cells induced by adenovirus-associated virus mediated CDK2-shRNA. Chin J Control Endemic Dis. 30:135–136. 2015.(In Chinese).

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 : PubMed/NCBI

23 

Li H, Zhou F, Wang H, Lin D, Chen G, Zuo X, Sun L, Zhang X and Yang S: Knockdown of myosin VI by lentivirus-mediated short hairpin RNA suppresses proliferation of melanoma. Mol Med Rep. 12:6801–6806. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Song Z, Lin J, Sun Z, Ni J and Sha Y: RNAi-mediated downregulation of CDKL1 inhibits growth and colony-formation ability, promotes apoptosis of human melanoma cells. J Dermatol Sci. 79:57–63. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Zhang YQ, Pei JH, Shi SS, Guo XS, Cui GY, Li YF, Zhang HP and Hu WQ: CRISPR/Cas9-mediated knockout of the PDEF gene inhibits migration and invasion of human gastric cancer AGS cells. Biomed Pharmacother. 111:76–85. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Yao S, He Z and Chen C: CRISPR/Cas9-mediated genome editing of epigenetic factors for cancer therapy. Hum Gene Ther. 26:463–471. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Zhen S and Li X: Oncogenic human papillomavirus: Application of CRISPR/Cas9 therapeutic strategies for cervical cancer. Cell Physiol Biochem. 44:2455–2466. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Biagioni A, Laurenzana A, Margheri F, Chilla A, Fibbi G and So M: Delivery systems of CRISPR/Cas9-based cancer gene therapy. J Biol Eng. 12:332018. View Article : Google Scholar : PubMed/NCBI

29 

Martín A, Odajima J, Hunt SL, Dubus P, Ortega S, Malumbres M and Barbacid M: Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1). Cancer Cell. 7:591–598. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Peng C, Zeng W, Su J, Kuang Y, He Y, Zhao S, Zhang J, Ma W, Bode AM, Dong Z and Chen X: Cyclin-dependent kinase 2 (CDK2) is a key mediator for EGF-induced cell transformation mediated through the ELK4/c-Fos signaling pathway. Oncogene. 35:1170–1179. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Bacevic K, Lossaint G, Achour TN, Georget V, Fisher D and Dulic V: Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced by DNA damage. Sci Rep. 7:134292017. View Article : Google Scholar : PubMed/NCBI

32 

Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelson T, Heckl D, Ebert BL, Root DE, Doench JG and Zhang F: Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 343:84–87. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera MC and Yusa K: Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol. 32:267–273. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Kale J, Osterlund EJ and Andrews DW: BCL-2 family proteins: Changing partners in the dance towards death. Cell Death Differ. 25:65–80. 2018. View Article : Google Scholar

35 

Adams JM and Cory S: The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ. 25:27–36. 2018. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu H, Li Z, Huo S, Wei Q and Ge L: Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes. Mol Clin Oncol 12: 9-14, 2020.
APA
Liu, H., Li, Z., Huo, S., Wei, Q., & Ge, L. (2020). Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes. Molecular and Clinical Oncology, 12, 9-14. https://doi.org/10.3892/mco.2019.1952
MLA
Liu, H., Li, Z., Huo, S., Wei, Q., Ge, L."Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes". Molecular and Clinical Oncology 12.1 (2020): 9-14.
Chicago
Liu, H., Li, Z., Huo, S., Wei, Q., Ge, L."Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes". Molecular and Clinical Oncology 12, no. 1 (2020): 9-14. https://doi.org/10.3892/mco.2019.1952
Copy and paste a formatted citation
x
Spandidos Publications style
Liu H, Li Z, Huo S, Wei Q and Ge L: Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes. Mol Clin Oncol 12: 9-14, 2020.
APA
Liu, H., Li, Z., Huo, S., Wei, Q., & Ge, L. (2020). Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes. Molecular and Clinical Oncology, 12, 9-14. https://doi.org/10.3892/mco.2019.1952
MLA
Liu, H., Li, Z., Huo, S., Wei, Q., Ge, L."Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes". Molecular and Clinical Oncology 12.1 (2020): 9-14.
Chicago
Liu, H., Li, Z., Huo, S., Wei, Q., Ge, L."Induction of G0/G1 phase arrest and apoptosis by CRISPR/Cas9‑mediated knockout of CDK2 in A375 melanocytes". Molecular and Clinical Oncology 12, no. 1 (2020): 9-14. https://doi.org/10.3892/mco.2019.1952
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