COMMD1, from the repair of DNA double strand breaks, to a novel anti-cancer therapeutic target
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Description
Lung cancer has the highest incidence and mortality among all cancers, with non-small cell lung cancer (NSCLC) accounting for 85–90% of all lung cancers. Here we investigated the function of COMMD1 in the repair of DNA double strand breaks (DSBs) and as a prognostic and therapeutic target in NSCLC. COMMD1 function in DSB repair was investigated using reporter assays in COMMD1-siRNA-depleted cells. The role of COMMD1 in NSCLC was investigated using bioinformatic analysis, qRT-PCR and immunoblotting of control and NSCLC cells, tissue microarrays, cell viability and cell cycle experiments. DNA repair assays demonstrated that COMMD1 is required for the efficient repair of DSBs and reporter assays showed that COMMD1 functions in both non-homologous-end-joining and homologous recombination. Bioinformatic analysis showed that COMMD1 is upregulated in NSCLC, with high levels of COMMD1 associated with poor patient prognosis. COMMD1 mRNA and protein were upregulated across a panel of NSCLC cell lines and siRNA-mediated depletion of COMMD1 decreased cell proliferation and reduced cell viability of NSCLC, with enhanced death after exposure to DNA damaging-agents. Bioinformatic analyses demonstrated that COMMD1 levels positively correlate with the gene ontology DNA repair gene set enrichment signature in NSCLC. Taken together, COMMD1 functions in DSB repair, is a prognostic maker in NSCLC and is potentially a novel anti-cancer therapeutic target for NSCLC.
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ID Code: | 209363 | ||||||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||||||
Refereed: | Yes | ||||||||||
ORCID iD: |
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Additional Information: | Funding Information: Funding: This research was funded by a generous grant from Yancoal, a William and Hilde Chen-hall Research Trust Research Award (D.J.R) and an IHBI Strategic Fellowship (M.N.A). | ||||||||||
Measurements or Duration: | 20 pages | ||||||||||
Keywords: | COMMD1, DNA double strand break repair, Genomic stability, Non-small cell lung cancer, Novel therapeutic target | ||||||||||
DOI: | 10.3390/cancers13040830 | ||||||||||
ISSN: | 2072-6694 | ||||||||||
Pure ID: | 81119491 | ||||||||||
Divisions: | Current > Research Centres > Centre for Genomics and Personalised Health Current > QUT Faculties and Divisions > Faculty of Health Current > Schools > School of Biomedical Sciences |
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Funding Information: | Funding: This research was funded by a generous grant from Yancoal, a William and Hilde Chen-hall Research Trust Research Award (D.J.R) and an IHBI Strategic Fellowship (M.N.A). | ||||||||||
Copyright Owner: | 2021 The Author(s) | ||||||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||||||
Deposited On: | 08 Apr 2021 05:42 | ||||||||||
Last Modified: | 24 Jun 2024 17:19 |
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