Subtype-specific dysregulation of biogenic amine-related genes and miRNAs in breast cancer: identification of DRD2, HRH2, and HRH4 as potential therapeutic targets in TNBC and HER2+ subtypes.
Agata Sirek, Tomasz Sirek, Robert Nowakowski, Przemysław Borawski, Piotr Ossowski, Katarzyna Mitka-Krysiak, Nikola Zmarzły, Kacper Boroń, Michał Chalcarz, Bernadeta Kuraszewska, Mariola Szulik, Dariusz Boroń, Beniamin Oskar Grabarek
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引用次数: 0
Abstract
Purpose: Biogenic amines (BAs) are known to influence tumorigenesis, yet their precise role in breast cancer remains unclear. This study aimed to investigate the expression patterns of BA-related genes, proteins, and their regulatory miRNAs across different breast cancer subtypes to identify potential biomarkers and therapeutic targets.
Methods: A cohort of 501 breast cancer patients was classified into luminal A (n = 130), luminal B HER2- (n = 100), luminal B HER2+ (n = 96), non-luminal HER2+ (n = 36), and triple-negative breast cancer (TNBC; n = 43). Gene expression was assessed via microarray analysis and validated using RT-qPCR. Protein levels were quantified using ELISA, while miRNA profiling was conducted to identify post-transcriptional regulatory interactions. Statistical significance was determined using ANOVA and Tukey's post-hoc test (p < 0.05).
Results: Histamine-related genes (HRH1-HRH4) were upregulated across all subtypes, with HRH2 and HRH4 most elevated in TNBC (FC = 7.18, p < 0.01). DRD2 showed widespread upregulation (FC = 15.98, p < 0.001), whereas DRD5 was markedly downregulated, especially in non-luminal HER2+ tumors (FC = - 13.01, p < 0.01). miRNA analysis revealed downregulation of hsa-miR-30b-3p and hsa-miR-372-5p in TNBC and HER2+ subtypes, correlating with HRH2 and HRH4 overexpression (p < 0.05). EGR1 and ICAM1 exhibited strong subtype-specific expression, with ICAM1 significantly upregulated in TNBC (FC = 25.76, p < 0.001).
Conclusion: Subtype-specific dysregulation of BA-related genes and miRNAs suggests their involvement in tumor progression, immune modulation, and metabolic regulation. The findings highlight potential therapeutic targets, particularly in TNBC and HER2+ subtypes.
期刊介绍:
Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.