Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers

Tommasi, Chiara; Pellegrino, Benedetta; Boggiani, Daniela; Sikokis, Angelica; Michiara, Maria; Uliana, Vera; Bortesi, Beatrice; Bonatti, Francesco; Mozzoni, Paola; Pinelli, Silvana; Squadrilli, Anna; Viani, Maria Vittoria; Cassi, Diana; Maglietta, Giuseppe; Meleti, Marco; Musolino, Antonino

doi:10.3389/fonc.2021.700853

Cited by 9 publications

(8 citation statements)

References 100 publications

(166 reference statements)

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“…Dysregulated expression of miR-21 and miR-155 may exacerbate the effects of BRCA mutations on tumorigenesis. BRCA mutations are involved in DNA repair mechanisms, and their dysfunction can lead to genomic instability and increased susceptibility to BC . The interplay between miR-21, miR-155, and BRCA mutations may further disrupt DNA repair processes, impacting genomic instability and promoting tumor development.…”

Section: Discussionmentioning

confidence: 99%

“…BRCA mutations are involved in DNA repair mechanisms, and their dysfunction can lead to genomic instability and increased susceptibility to BC. 50 The interplay between miR-21, miR-155, and BRCA mutations may further disrupt DNA repair processes, impacting genomic instability and promoting tumor development. Moreover, miR-21 and miR-155 may modulate the sensitivity of BRCA -mutated BC cells to therapeutic interventions, such as PARP inhibitors.…”

Section: Discussionmentioning

confidence: 99%

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BRCA Mutations and MicroRNA Expression Patterns in the Peripheral Blood of Breast Cancer Patients

Alavanda,

Dirimtekin,

Mortoglou

et al. 2024

ACS Omega

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Breast cancer (BC) persists as the predominant malignancy globally, standing as the foremost cause of cancer-related mortality among women. Despite notable advancements in prevention and treatment, encompassing the incorporation of targeted immunotherapies, a continued imperative exists for the development of innovative methodologies. These methodologies would facilitate the identification of women at heightened risk, enhance the optimization of therapeutic approaches, and enable the vigilant monitoring of emergent treatment resistance. Circulating microRNAs (miRNAs), found either freely circulating in the bloodstream or encapsulated within extracellular vesicles, have exhibited substantial promise for diverse clinical applications. These applications range from diagnostic and prognostic assessments to predictive purposes. This study aimed to explore the potential associations between BRCA mutations and specific miRNAs (miR-21, miR-155, miR-126, and miR-200c) expression that are known to be dysregulated in BC patient samples. Our findings indicate a robust correlation between miRNA expression status and disease subtypes. We found a correlation between the expression status of miRNAs and distinct disease subtypes. Intriguingly, however, no significant associations were discerned between disease status, subtypes, or miRNA expression levels and the presence of BRCA mutations. To advance the validation of miRNAs as clinically relevant biomarkers, additional investigations within larger and meticulously selected patient cohorts are deemed imperative. These microRNA entities hold the potential to emerge as groundbreaking and readily accessible tools, poised for seamless integration into the landscape of clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

BRCA Mutations and MicroRNA Expression Patterns in the Peripheral Blood of Breast Cancer Patients

Alavanda,

Dirimtekin,

Mortoglou

et al. 2024

ACS Omega

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“…The individual expression levels of miRNAs were detected by the RT-qPCR technique using the QuantStudio 3 equipment (Thermo Fisher Scientific, Massachusetts, United States) and the TaqMan Fast Advanced Master Mix assay (Thermo Fisher Scientific, Massachusetts, United States), under standard cycling conditions, according to the manufacturer’s recommendations. The amplification reaction consisted of 50 ng of cDNA, TaqMan Master Mix, and a specific probe for each miRNA: hsa-miR-1-3p (ID 002222, miRbase MI0000651) ( Liu et al, 2017 ; Wu, 2018 ; Peng et al, 2020 ; Chen et al, 2021 ); hsa-miR-16-5p (ID 000391, miRbase MI0000070) ( Qu et al, 2017 ; Tommasi et al, 2021 ; Wang et al, 2021 ); hsa-miR-21-5p (ID 000397, miRbase MI0000077) ( Wu et al, 2012 ; Li et al, 2016 ; Chen et al, 2019 ; Wang et al, 2019 ); hsa-miR-210-3p (ID 000512, miRbase MI0000286) ( Evangelista et al, 2021 ; Khalilian et al, 2023 ; Santana et al, 2023 ); hsa-miR-195-5p (ID 000494, miRbase MI0000489) ( Singh et al, 2015 ; McAnena et al, 2019 ; Chen et al, 2022 ); hsa-miR-10b-5p (ID 002218, miRbase MI0000267) ( Han et al, 2014 ; Nassar et al, 2014 ; Zhang et al, 2018 ; Raval et al, 2022 ), and hsa-miR-34a-5p (ID 000426, MI0000268) ( Peurala et al, 2011 ; Misso et al, 2014 ; Zaleski et al, 2018 ; Chen et al, 2021 ). Assay ID for TaqMan MicroRNA Assay, Thermo Fisher Scientific.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA as a promising molecular biomarker in the diagnosis of breast cancer

Miranda,

Slaibi-Filho,

Calasans dos Santos

et al. 2024

Front. Mol. Biosci.

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Introduction: Breast cancer represents the most prevalent malignancy among women. Recent advancements in translational research have focused on the identification of novel biomarkers capable of providing valuable insights into patient outcomes. Furthermore, comprehensive investigations aimed at discovering novel miRNAs, unraveling their biological functions, and deciphering their target genes have significantly contributed to our understanding of the roles miRNAs play in tumorigenesis. Consequently, these investigations have facilitated the way for the development of miRNA-based approaches for breast cancer prognosis, diagnosis, and treatment. However, conducting a more extensive array of studies, particularly among diverse ethnic groups, is imperative to expand the scope of research and validate the significance of miRNAs. This study aimed to assess the expression patterns of circulating miRNAs in plasma as a prospective biomarker for breast cancer patients within a population primarily consisting of individuals from Black, Indigenous, and People of Color (BIPOC) communities.Methods: We evaluated 49 patients with breast cancer compared to 44 healthy women.Results and discussion: All miRNAs analyzed in the plasma of patients with breast cancer were downregulated. ROC curve analysis of miR-21 (AUC = 0.798, 95% CI: 0.682–0.914, p <0.0001), miR-1 (AUC = 0.742, 95% CI: 0.576–0.909, p = 0.004), miR-16 (AUC = 0.721, 95% CI: 0.581–0.861, p = 0.002) and miR-195 (AUC = 0.672, 95% CI: 0.553–0.792, p = 0.004) showed better diagnostic accuracy in discrimination of breast cancer patients in comparison with healthy women. miR-210, miR-21 showed the highest specificities values (97.3%, 94.1%, respectively). Following, miR-10b and miR-195 showed the highest sensitivity values (89.3%, and 77.8%, respectively). The panel with a combination of four miRNAs (miR-195 + miR-210 + miR-21 + miR-16) had an AUC of 0.898 (0.765–0.970), a sensitivity of 71.4%, and a specificity of 100.0%. Collectively, our results highlight the miRNA combination in panels drastically improves the results and showed high accuracy for the diagnosis of breast cancer displaying good sensitivity and specificity.

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“…Differential miRNA expressions can be caused by genetic variation, and variants within miRNA could, thus, affect the allelic expression and modify the penetrance or expressivity of monogenic diseases ( Cammaerts et al, 2015 ). The expression of numerous miRNAs may affect the penetrance and expressivity in hereditary breast and ovarian cancer (HBOC) ( Tommasi et al, 2021 ); incomplete and age-dependent penetrance is common in carriers of pathogenic variants in BRCA1 and BRCA2, and variation in several miRNAs that bind the 3′UTRs and downregulate the expression of both genes have been linked with an increased risk of earlier onset cancer ( Chen and Parmigiani, 2007 ; Chang et al, 2011 ; Moskwa et al, 2011 ; Sun et al, 2013 ; Tommasi et al, 2021 ).…”

Section: Gene Expressionmentioning

confidence: 99%

Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts

Kingdom

Wright

2022

Front. Genet.

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The same genetic variant found in different individuals can cause a range of diverse phenotypes, from no discernible clinical phenotype to severe disease, even among related individuals. Such variants can be said to display incomplete penetrance, a binary phenomenon where the genotype either causes the expected clinical phenotype or it does not, or they can be said to display variable expressivity, in which the same genotype can cause a wide range of clinical symptoms across a spectrum. Both incomplete penetrance and variable expressivity are thought to be caused by a range of factors, including common variants, variants in regulatory regions, epigenetics, environmental factors, and lifestyle. Many thousands of genetic variants have been identified as the cause of monogenic disorders, mostly determined through small clinical studies, and thus, the penetrance and expressivity of these variants may be overestimated when compared to their effect on the general population. With the wealth of population cohort data currently available, the penetrance and expressivity of such genetic variants can be investigated across a much wider contingent, potentially helping to reclassify variants that were previously thought to be completely penetrant. Research into the penetrance and expressivity of such genetic variants is important for clinical classification, both for determining causative mechanisms of disease in the affected population and for providing accurate risk information through genetic counseling. A genotype-based definition of the causes of rare diseases incorporating information from population cohorts and clinical studies is critical for our understanding of incomplete penetrance and variable expressivity. This review examines our current knowledge of the penetrance and expressivity of genetic variants in rare disease and across populations, as well as looking into the potential causes of the variation seen, including genetic modifiers, mosaicism, and polygenic factors, among others. We also considered the challenges that come with investigating penetrance and expressivity.

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Biological Role and Clinical Implications of microRNAs in BRCA Mutation Carriers

Cited by 9 publications

References 100 publications

BRCA Mutations and MicroRNA Expression Patterns in the Peripheral Blood of Breast Cancer Patients

BRCA Mutations and MicroRNA Expression Patterns in the Peripheral Blood of Breast Cancer Patients

MicroRNA as a promising molecular biomarker in the diagnosis of breast cancer

Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts

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