Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening View Full Text


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Article Info

DATE

2014-12-13

AUTHORS

Zongxiang Zhou, Manishha Patel, Nicholas Ng, Mindy H Hsieh, Anthony P Orth, John R Walker, Serge Batalov, Jennifer L Harris, Jun Liu

ABSTRACT

BACKGROUND: MYC family members are among the most frequently deregulated oncogenes in human cancers, yet direct therapeutic targeting of MYC in cancer has been challenging thus far. Synthetic lethality provides an opportunity for therapeutic intervention of MYC-driven cancers. METHODS: A pooled kinase shRNA library screen was performed and next-generation deep sequencing efforts identified that PRKDC was synthetically lethal in cells overexpressing MYC. Genes and proteins of interest were knocked down or inhibited using RNAi technology and small molecule inhibitors, respectively. Quantitative RT-PCR using TaqMan probes examined mRNA expression levels and cell viability was assessed using CellTiter-Glo (Promega). Western blotting was performed to monitor different protein levels in the presence or absence of RNAi or compound treatment. Statistical significance of differences among data sets were determined using unpaired t test (Mann-Whitney test) or ANOVA. RESULTS: Inhibition of PRKDC using RNAi (RNA interference) or small molecular inhibitors preferentially killed MYC-overexpressing human lung fibroblasts. Moreover, inducible PRKDC knockdown decreased cell viability selectively in high MYC-expressing human small cell lung cancer cell lines. At the molecular level, we found that inhibition of PRKDC downregulated MYC mRNA and protein expression in multiple cancer cell lines. In addition, we confirmed that overexpression of MYC family proteins induced DNA double-strand breaks; our results also revealed that PRKDC inhibition in these cells led to an increase in DNA damage levels. CONCLUSIONS: Our data suggest that the synthetic lethality between PRKDC and MYC may in part be due to PRKDC dependent modulation of MYC expression, as well as MYC-induced DNA damage where PRKDC plays a key role in DNA damage repair. More... »

PAGES

944

References to SciGraph publications

  • 2003-06-09. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks in NATURE CELL BIOLOGY
  • 2006. Structural Aspects of Interactions Within the Myc/Max/Mad Network in THE MYC/MAX/MAD TRANSCRIPTION FACTOR NETWORK
  • 2007-06-24. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC in NATURE MEDICINE
  • 2008-07. Ras oncogenes: split personalities in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2011-03-07. Targeting the missing links for cancer therapy in NATURE MEDICINE
  • 1983-02. A severe combined immunodeficiency mutation in the mouse in NATURE
  • 2008-09-15. Drug discovery approaches targeting the PI3K/Akt pathway in cancer in ONCOGENE
  • 2012-03-28. Deregulated MYC expression induces dependence upon AMPK-related kinase 5 in NATURE
  • 2011-08-03. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia in NATURE
  • 2010-02. The landscape of somatic copy-number alteration across human cancers in NATURE
  • 2008-08-17. Modelling Myc inhibition as a cancer therapy in NATURE
  • 2005-08-19. The Concept of Synthetic Lethality in the Context of Anticancer Therapy in NATURE REVIEWS CANCER
  • 1993-05. Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain in NATURE
  • 2008-11-30. Effective Use of PI3K and MEK Inhibitors to Treat Mutant K-Ras G12D and PIK3CA H1047R Murine Lung Cancers in NATURE MEDICINE
  • 2007-05-14. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer in ONCOGENE
  • 2011-11-27. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2004-05-14. Omomyc expression in skin prevents Myc-induced papillomatosis in CELL DEATH & DIFFERENTIATION
  • 2013-01-17. Identification of DNA-dependent protein kinase catalytic subunit as a novel interaction partner of lymphocyte enhancer factor 1 in MEDICAL MOLECULAR MORPHOLOGY
  • 2011-04-29. Harnessing synthetic lethal interactions in anticancer drug discovery in NATURE REVIEWS DRUG DISCOVERY
  • 1996. The DNA-Activated Protein Kinase — DNA-PK in MOLECULAR ANALYSIS OF DNA REARRANGEMENTS IN THE IMMUNE SYSTEM
  • 2008-04-22. DNA-dependent protein kinase catalytic subunit modulates the stability of c-Myc oncoprotein in MOLECULAR CANCER
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    http://scigraph.springernature.com/pub.10.1186/1471-2407-14-944

    DOI

    http://dx.doi.org/10.1186/1471-2407-14-944

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1030949329

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25495526


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