The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
miR-182-Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors
Open accessAbstract
Expression of BRCA1 is commonly decreased in sporadic breast tumors, and this correlates with poor prognosis of breast cancer patients. Here we show that BRCA1 transcripts are selectively enriched in the Argonaute/miR-182 complex and miR-182 down-regulates BRCA1 expression . Antagonizing miR-182 enhances BRCA1 protein levels and protects them from IR-induced cell death, while overexpressing miR-182 reduces BRCA1 protein, impairs homologous recombination-mediated repair, and render cells hypersensitive to IR. The impaired DNA repair phenotype induced by miR-182 overexpression can be fully rescued by over-expressing miR-182-insensitive BRCA1. Consistent with a BRCA1-deficiency phenotype, miR-182 overexpressing breast tumor cells are hypersensitive to inhibitors of poly (ADP-ribose) polymerase1 (PARP1). Conversely, antagonizing miR-182 enhances BRCA1 levels and induces resistance to PARP1 inhibitor. Finally, a clinical-grade PARP1 inhibitor impacts outgrowth of miR-182 expressing tumors in animal models. Together these results suggest that miR-182-mediated down-regulation of BRCA1 impedes DNA repair, and may impact breast cancer therapy.
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Citations
Cites
MicroRNAs: Target Recognition and Regulatory Functions
Bartel, D. P. (2009) · Cell · doi:10.1016/j.cell.2009.01.002 · Cited by 20,068
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198
Self-citationInhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634
Regulation of mRNA Translation and Stability by microRNAs
Fabian, M. R., Sonenberg, N., & Filipowicz, W. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060308-103103 · Cited by 3,214
Brca1 Controls Homology-Directed DNA Repair
Moynahan, M. E., Chiu, J. W., Koller, B. H., & Jasin, M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80202-6 · Cited by 1,245
Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors
Esteller, M. (2000) · Journal of the National Cancer Institute · doi:10.1093/jnci/92.7.564 · Cited by 1,233 · cited 2×
“Although promoter methylation may result in very low levels of BRCA1, aberrant methylation of the BRCA1 promoter is found only in a relatively moderate percentage (10%–15%) of sporadic breast tumors (Catteau et al., 1999; Esteller et al., 2000; Matros et al., 2005; Rice et al., 2000), and there is no significant corre…”
BRCA1 and BRCA2: 1994 and beyond
Narod, S. A., & Foulkes, W. D. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1431 · Cited by 967
Gaur, A., Jewell, D. A., Liang, Y., Ridzon, D., Moore, J. H., Chen, C., Ambros, V. R., & Israel, M. A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2698 · Cited by 727
Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair
Nakanishi, K., Yang, Y.-G., Pierce, A. J., Taniguchi, T., Digweed, M., D'Andrea, A. D., Wang, Z.-Q., & Jasin, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407796102 · Cited by 384 · cited 1×
“To test whether expression of miR-182 impacts HR repair, we assayed for HR-mediated repair of an I-SceI-induced DSB, in U2OS cells, using a recombination substrate DR-GFP (Nakanishi et al., 2005).”
Cited by
The DNA damage response and cancer therapy
Lord, C. J., & Ashworth, A. (2012) · Nature · doi:10.1038/nature10760 · Cited by 1,649
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer
Konstantinopoulos, P. A., Ceccaldi, R., Shapiro, G. I., & D'Andrea, A. D. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0714 · Cited by 945
Synthetic lethality of PARP inhibition in cancers lacking BRCA1 and BRCA2 mutations
Dedes, K. J., Wilkerson, P. M., Wetterskog, D., Weigelt, B., Ashworth, A., & Reis-Filho, J. S. (2011) · Cell Cycle · doi:10.4161/cc.10.8.15273 · Cited by 191
Genomic integrity and the ageing brain
Chow, H.-M., & Herrup, K. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4020 · Cited by 174
Eukaryotic DNA damage checkpoint activation in response to double-strand breaks
Finn, K., Lowndes, N. F., & Grenon, M. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0875-3 · Cited by 127
Metadata
- Authors
- Moskwa, P., Buffa, F. M., Pan, Y., Panchakshari, R., Gottipati, P., Muschel, R. J., Beech, J., Kulshrestha, R., Abdelmohsen, K., Weinstock, D. M., Gorospe, M., Harris, A. L., Helleday, T., & Chowdhury, D.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 41
- Issue
- 2
- Pages
- 210-220
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2118723994
- Cited by
- 430
- References
- 15
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Moskwa, P., Buffa, F. M., Pan, Y., Panchakshari, R., Gottipati, P., Muschel, R. J., Beech, J., Kulshrestha, R., Abdelmohsen, K., Weinstock, D. M., Gorospe, M., Harris, A. L., Helleday, T., & Chowdhury, D. (2011). miR-182-Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors. Molecular Cell. https://doi.org/10.1016/j.molcel.2010.12.005
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
