ArticleBMC cancer2014
Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Synthetic lethality in cancer: a protocol for scoping review of gene interactions from synthetic lethal screens and functional studies.Systematic reviews · 2025Article
- The leading role of MYC in DNA damage response: exploring opportunities for therapeutic inhibition.Frontiers in cell and developmental biology · 2025Review
- Exploiting replication stress for synthetic lethality in MYC-driven cancers.American journal of cancer research · 2025Review
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Myeloid cell differentiation-related gene signature for predicting clinical outcome, immune microenvironment, and treatment response in lung adenocarcinoma.Scientific reports · 2024Article
- Topoisomerase 1 Inhibition in MYC-Driven Cancer Promotes Aberrant R-Loop Accumulation to Induce Synthetic Lethality.Cancer research · 2023Article
- Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa.Nature communications · 2023Article
- A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics.Nature communications · 2023Article
- CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells.Molecular oncology · 2023Article
- Discovery and Characterization of ZL-2201, a Potent, Highly Selective, and Orally Bioavailable Small-molecule DNA-PK Inhibitor.Cancer research communications · 2023Article
- DNA Ligase 4 Contributes to Cell Proliferation against DNA-PK Inhibition inInternational journal of molecular sciences · 2023Article
- Alternative approaches to target Myc for cancer treatment.Signal transduction and targeted therapy · 2021Review
- The UVSSA complex alleviates MYC-driven transcription stress.The Journal of cell biology · 2021Article
- The SUMO pathway in pancreatic cancer: insights and inhibition.British journal of cancer · 2021Review
- Evaluation of gene expression levels in the diagnosis of lung adenocarcinoma and malignant pleural mesothelioma.Turk gogus kalp damar cerrahisi dergisi · 2020Article
- High expression of PRKDC promotes breast cancer cell growth via p38 MAPK signaling and is associated with poor survival.Molecular genetics & genomic medicine · 2019Article
- Comprehensive in vivo identification of the c-Myc mRNA protein interactome using HyPR-MS.RNA (New York, N.Y.) · 2019Article
- Modelling the MYC-driven normal-to-tumour switch in breast cancer.Disease models & mechanisms · 2019Article
- Acquisition of Cancer Stem Cell-like Properties in Human Small Airway Epithelial Cells after a Long-term Exposure to Carbon Nanomaterials.Environmental science. Nano · 2019Article
- Interaction network analysis of YBX1 for identification of therapeutic targets in adenocarcinomas.Journal of biosciences · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMYC 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.
methodsA 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.
resultsInhibition 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.
conclusionsOur 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.