Direct DNA binding by BRCA1 on β-hCG promoter and its clinical implications

Autor: Neethu Krishnan, Neetha R L, Arathy V. Warrier, Induprabha Yadev, Jaimie Anandan, Sankar Sundaram, Arathi Rajan, Prianka Kumari, Shreya Sara Ittycheria, Manasa V.G, Serbin Mohammed, Preethamol S, Rakesh Sathish Nair, Priya Srinivas
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 17, Pp e37064- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e37064
Popis: Objective: The role of β-hCG in breast cancer is largely unknown, this study aims to analyse the gene expression and clinical implications of β-hCG and its isoforms in various cancers focussing particularly in Breast Invasive Carcinoma (BRCA). A mechanistic approach deciphering the transcriptional regulation of β-hCG by BRCA1 was also explored. Methods: Data from various comprehensive gene expression platforms like UALCAN, GEPIA2, GENT2, TIMER2, LinkedOmics, and STRING were used to analyse the expression of β-hCG and its clinical implications; Immunohistochemistry and ELISA for β-hCG expression analysis from human breast cancer patients; Electrophoretic mobility shift assay (EMSA) to analyse the direct binding of BRCA1 on β-hCG; Immunoblotting and Luciferase assay to understand the regulation of β-hCG by p53 were performed. Results: Results from UALCAN and GENT2 gene expression cancer database revealed that TNBC subtypes and high-grade metaplastic carcinoma shows elevated expression of β-hCG and infiltration of various immune cells were also identified in BRCA by TIMER2. It was observed that most of the isoforms of β-hCG (CGB) are upregulated in breast cancers irrespective of hormonal status when BRCA1 gene is mutated according to TIMER2. Similar results were observed with Lymphoid neoplasm diffuse large B-cell lymphoma (LGG) and DLBC (Brain lower grade glioma) when BRCA1 is mutated. These results correlate with our earlier reports indicating expression of β-hCG in BRCA1 defective condition. We have also identified direct binding of BRCA1 on β-hCG promoter. Conclusion: All these findings demonstrate the importance of β-hCG as a potential target in BRCA1-deficient carcinomas.
Databáze: Directory of Open Access Journals