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

Autor:	Krishnan N; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.; Research Centre, University of Kerala, Thiruvananthapuram, Kerala, India., R L N; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India., Warrier AV; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.; Research Centre, University of Kerala, Thiruvananthapuram, Kerala, India., Yadev I; Government Medical College, Thiruvananthapuram, Kerala, India.; Government Medical College, Kollam, Kerala, India., Anandan J; Government Medical College, Thiruvananthapuram, Kerala, India., Sundaram S; Government Medical College, Kottayam, Kerala, India., Rajan A; Institute of Advanced Virology, Thiruvananthapuram, Kerala, India., Kumari P; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.; DBT-Regional Centre for Biotechnology (RCB), Faridabad, 121001, Haryana, India., Ittycheria SS; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.; Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India., V G M; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India., Mohammed S; Government Medical College, Thiruvananthapuram, Kerala, India.; Government Medical College, Kollam, Kerala, India., S P; Government Medical College, Thiruvananthapuram, Kerala, India., Nair RS; Department of Surgery, Division of Surgical Oncology, The University of Illinois at Chicago, Chicago, IL, 60612, USA., Srinivas P; Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.; DBT-Regional Centre for Biotechnology (RCB), Faridabad, 121001, Haryana, India.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Aug 30; Vol. 10 (17), pp. e37064. Date of Electronic Publication: 2024 Aug 30 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e37064
Abstrakt:	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. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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