دورية أكاديمية
أعرض في EDS

Assessing the Impact of Novel BRCA1 Exon 11 Variants on Pre-mRNA Splicing.

التفاصيل البيبلوغرافية
العنوان: Assessing the Impact of Novel BRCA1 Exon 11 Variants on Pre-mRNA Splicing.
المؤلفون: Elshwekh H; International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.; Department of Genetic Engineering, Libyan Biotechnology Research Center, Tripoli P.O. Box 30313, Libya., Alhudiri IM; Department of Genetic Engineering, Libyan Biotechnology Research Center, Tripoli P.O. Box 30313, Libya., Elzagheid A; Department of Genetic Engineering, Libyan Biotechnology Research Center, Tripoli P.O. Box 30313, Libya., Enattah N; Department of Genetic Engineering, Libyan Biotechnology Research Center, Tripoli P.O. Box 30313, Libya., Abbassi Y; International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy., Abou Assali L; International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy., Marino I; International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.; Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK., Stuani C; International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy., Buratti E; International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy., Romano M; Department of Life Sciences, University of Trieste, Via A. Valerio, 28, 34127 Trieste, Italy.
المصدر: Cells [Cells] 2024 May 11; Vol. 13 (10). Date of Electronic Publication: 2024 May 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Exons*/genetics , BRCA1 Protein*/genetics , BRCA1 Protein*/metabolism , RNA Precursors*/genetics , RNA Precursors*/metabolism , RNA Splicing*/genetics , Breast Neoplasms*/genetics , Breast Neoplasms*/pathology, Humans ; Female ; Cell Line, Tumor ; Mutation/genetics ; MCF-7 Cells ; Alternative Splicing/genetics ; Genetic Predisposition to Disease
مستخلص: Our study focused on assessing the effects of three newly identified BRCA1 exon 11 variants (c.1019T>C, c.2363T>G, and c.3192T>C) on breast cancer susceptibility. Using computational predictions and experimental splicing assays, we evaluated their potential as pathogenic mutations. Our in silico analyses suggested that the c.2363T>G and c.3192T>C variants could impact both splicing and protein function, resulting in the V340A and V788G mutations, respectively. We further examined their splicing effects using minigene assays in MCF7 and SKBR3 breast cancer cell lines. Interestingly, we found that the c.2363T>G variant significantly altered splicing patterns in MCF7 cells but not in SKBR3 cells. This finding suggests a potential influence of cellular context on the variant's effects. While attempts to correlate in silico predictions with RNA binding factors were inconclusive, this observation underscores the complexity of splicing regulation. Splicing is governed by various factors, including cellular contexts and protein interactions, making it challenging to predict outcomes accurately. Further research is needed to fully understand the functional consequences of the c.2363T>G variant in breast cancer pathogenesis. Integrating computational predictions with experimental data will provide valuable insights into the role of alternative splicing regulation in different breast cancer types and stages.
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معلومات مُعتمدة: We STaR project Italian MAECI/DGCS
فهرسة مساهمة: Keywords: BRCA1; S1064S; V340A; V788G; breast cancer; c.1019T>C; c.2363T>G; c.3192T>C; exon 11; functional genetics; germline mutations; loss of heterozygosity; splicing
المشرفين على المادة: 0 (BRCA1 Protein)
0 (RNA Precursors)
0 (BRCA1 protein, human)
تواريخ الأحداث: Date Created: 20240524 Date Completed: 20240524 Latest Revision: 20240526
رمز التحديث: 20240526
مُعرف محوري في PubMed: PMC11119505
DOI: 10.3390/cells13100824
PMID: 38786046
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells13100824