miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype

Tommasi, Stefania; Pinto, Rosamaria; Danza, Katia; Pilato, Brunella; Palumbo, Orazio; Micale, Lucia; Summa, Simona De

doi:10.18632/oncotarget.10345

Cited by 22 publications

(20 citation statements)

References 36 publications

(39 reference statements)

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“…One breast cancer study had found that miR-361 was overexpressed in PARP1-upregulating BRCA -germline mutated and sporadic breast cancers. [39]. Another breast cancer study that examined 28 breast cancer samples observed that miR-361 upregulation was indicative of metastatic breast cancer, but an association with metastasis does not imply a statistically significant association with prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

et al. 2016

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Breast cancer is the second-most common cancer and second-leading cause of cancer mortality in American women. The dysregulation of microRNAs (miRNAs) plays a key role in almost all cancers, including breast cancer. We comprehensively analyzed miRNA expression, global gene expression, and patient survival from the Cancer Genomes Atlas (TCGA) to identify clinically relevant miRNAs and their potential gene targets in breast tumors. In our analysis, we found that increased expression of 12 mature miRNAs—hsa-miR-320a, hsa-miR-361-5p, hsa-miR-103a-3p, hsa-miR-21-5p, hsa-miR-374b-5p, hsa-miR-140-3p, hsa-miR-25-3p, hsa-miR-651-5p, hsa-miR-200c-3p, hsa-miR-30a-5p, hsa-miR-30c-5p, and hsa-let-7i-5p —each predicted improved breast cancer survival. Of the 12 miRNAs, miR-320a, miR-361-5p, miR-21-5p, miR-103a-3p were selected for further analysis. By correlating global gene expression with miRNA expression and then employing miRNA target prediction analysis, we suggest that the four miRNAs may exert protective phenotypes by targeting breast oncogenes that contribute to patient survival. We propose that miR-320a targets the survival-associated genes RAD51, RRP1B, and TDG; miR-361-5p targets ARCN1; and miR-21-5p targets MSH2, RMND5A, STAG2, and UBE2D3. The results of our stringent bioinformatics approach for identifying clinically relevant miRNAs and their targets indicate that miR-320a, miR-361-5p, and miR-21-5p may contribute to breast cancer survival.

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Section: Discussionmentioning

confidence: 99%

Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

et al. 2016

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“…In the last years, the attention has been drawn to molecular aberrations underlying DNA repair damage dysfunction in order to better select patients treatable with PARPi. A recent study showed the possibility of considering the overexpression of PARP1 and miR-151-5p as biomarkers useful to correctly treat sporadic breast cancers with PARPi [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

TGFbeta and miRNA regulation in familial and sporadic breast cancer

et al. 2017

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The term 'BRCAness' was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease. Affymetrix GeneChip microRNA Arrays were used to perform microRNA expression analysis in familial and sporadic breast cancer. Pathway enrichment analysis and microRNA target prediction was carried out using DIANA miRPath v.3 web-based computational tool and miRWalk v.2 database. We analyzed an external gene expression dataset (E-GEOD-49481), including both familial and sporadic breast cancers. For microRNA validation, an independent set of 19 familial and 10 sporadic breast cancers was used. Microarray analysis identified a signature of 28 deregulated miRNAs. For our validation analyses by real time PCR, we focused on miR-92a-1*, miR-1184 and miR-943 because associated to TGF-β signalling pathway, ATM and BRCA1 genes expression. Our results highlighted alterations in miR-92a-1*, miR-1184 and miR-943 expression levels suggesting their involvement in repair of DNA double-strand breaks through TGF-beta pathway control.

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“…Thus miR-664b-5p has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2 in BRCA1 not-mutated TNBC ( 93 ). Furthermore, an interesting mechanism involving miR-151-5p and its target SMARCA5, an ISWI family member with an important role in DSB repair ( 94 ), has been proposed. Indeed, Tommasi et al reported the possibility of considering the overexpression of PARP1 and miR-151-5p as predictive biomarkers, useful to correctly select sporadic breast cancers for treatment with PARP inhibitors.…”

Section: Micrornas Regulate Dna Repair Genes and Parp Inhibitor Respomentioning

confidence: 99%

MicroRNAs and DNA-Damaging Drugs in Breast Cancer: Strength in Numbers

2018

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MicroRNAs are a class of small non-coding regulatory RNAs playing key roles in cancer. Breast cancer is the most common female malignancy worldwide and is categorized into four molecular subtypes: luminal A and B, HER2+ and triple-negative breast cancer (TNBC). Despite the development of multiple targeted therapies for luminal and HER2+ breast tumors, TNBC lacks specific therapeutic approaches, thus they are treated mainly with radio- and chemotherapy. The effectiveness of these therapeutic regimens is based on their ability to induce DNA damage, which is differentially resolved and repaired by normal vs. cancer cells. Recently, drugs directly targeting DNA repair mechanisms, such as PARP inhibitors, have emerged as attractive candidates for the future molecular targeted-therapy in breast cancer. These compounds prevent cancer cells to appropriate repair DNA double strand breaks and induce a phenomenon called synthetic lethality, that results from the concurrent inhibition of PARP and the absence of functional BRCA genes which prompt cell death. MicroRNAs are relevant players in most of the biological processes including DNA damage repair mechanisms. Consistently, the downregulation of DNA repair genes by miRNAs have been probe to improve the therapeutic effect of genotoxic drugs. In this review, we discuss how microRNAs can sensitize cancer cells to DNA-damaging drugs, through the regulation of DNA repair genes, and examine the most recent findings on their possible use as a therapeutic tools of treatment response in breast cancer.

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miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype

Cited by 22 publications

References 36 publications

Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

TGFbeta and miRNA regulation in familial and sporadic breast cancer

MicroRNAs and DNA-Damaging Drugs in Breast Cancer: Strength in Numbers

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