miR-182-Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors

Moskwa, Patryk; Buffa, Francesca M.; Pan, Yuwei; Panchakshari, Rohit A.; Gottipati, Ponnari; Muschel, Ruth J.; Beech, John R.; Kulshrestha, Ritu; Abdelmohsen, Kotb; Weinstock, David M.; Gorospe, Myriam; Harris, Adrian L.; Helleday, Thomas; Chowdhury, Dipanjan

doi:10.1016/j.molcel.2013.12.015

Cited by 49 publications

(67 citation statements)

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“…Crippa et al 105 reported that miR-342 regulates BRCA1 expression by modulating the expression of inhibitor of differentiation 4, which in turn negatively regulates BRCA1 expression in breast cancer. Moskwa et al 106 suggested that miR-182 downregulates BRCA1 expression and found that the manipulation of miR-182 expression in breast cell lines affected their sensitivity to poly-ADP ribose polymerase (PARP) 1 inhibition. Tanic et al 107 recently investigated miRNA classifiers in an attempt to predict the BRCA germline mutation status of routinely available formalin-fixed, paraffin-embedded breast tumor biopsy samples based on 6 types of miRNA (miR-142-3p, miR-505, miR-1248, miR-181a-2, miR-25 and miR-340).…”

Section: Mirna In Triple-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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Section: Mirna In Triple-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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“…Other miRNAs, such as miR-7, miR-101 and miR-182, have been shown to target transcripts of DSB repair genes such as BRCA1 (breast cancer 1) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), respectively, and to radiosensitize cells in vitro as well as in xenograft models (47,49,50). In a panel of human cancer cells, overexpression of miR-7, for example, resulted in downregulation of EGFR and Akt, which was associated with decreased phosphorylation of DNA-PKcs and delayed DNA repair.…”

Section: Mirnas Modulating Dna Damage Responsementioning

confidence: 99%

MicroRNAs and Their Impact on Radiotherapy for Cancer

et al. 2016

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“…253 BRCA1/2 somatic and germline mutations are observed more frequently in ovarian (420%) as compared with breast cancers; 255 yet, the finding of a high response rate to PARP inhibitors in high-grade ovarian cancers suggests alternative mechanisms of HRR inactivation may operate in addition. Although the ovarian cancer genome atlas reported a low incidence of mutations in other genes involved in the Fanconi complex, 256 there may be other mechanisms involved, including miRNA-mediated downregulation of BRCA1, 257 which has been reported in triple-negative breast cancers. 258 Anecdotically, a remarkable response to mitomycin was observed in a patient with pancreatic cancer harbouring biallelic PALB2 mutations.…”

Section: Homologous Recombination Repairmentioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

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miR-182-Mediated Downregulation of BRCA1 Impacts DNA Repair and Sensitivity to PARP Inhibitors

Cited by 49 publications

References 0 publications

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

MicroRNAs and Their Impact on Radiotherapy for Cancer

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

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