Avicenna J Med Biotech

arij002

Avicenna Journal of Medical Biotechnology

2008-2835 2008-4625

Avicenna Research Institute

ajmb60537

Study of DACH1 Expression and its Epigenetic Regulators as Possible Breast Cancer-Related Biomarkers

Nasirpour

Mohammad Hossein

Salimi

Mahdieh

Diagnostic Laboratory Sciences and Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

Majidi

Faezeh

Minuchehr

Zarrin

Genetic Research Center, University of Social Welfare and Rehabilitation Science, Tehran, Iran

Mozdarani

Hossein

Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

15 2 108 117 15 10 2022 22 2 2023

Background: Breast carcinogenesis involves both genetic and epigenetic changes. DNA methylation, as well as micro-RNA regulations, are the significant epigenetic phenomena dysregulated in breast cancer. Herein, the expression of DACH1 as a tumor suppressor gene and its promoter methylation status was analyzed in breast cancer tumors. Also, the expression of three micro RNAs (miR-217, miR-6807-3p, and miR-552), which had been previously reported to target DACH1, was assessed.  Methods: The SYBR green-based Real-Time reverse transcription-PCR was used to determine DACH1 and micro-RNAs (miR-217, miR-6807-3p, and miR-552) expression in 120 ductal breast cancer tumors compared with standard control. Also, the promoter methylation pattern of DACH1 was investigated using the Methylation-specific PCR technique. Results: DACH1 expression was significantly down-regulated in breast tumors (p< 0.05). About 33.5% of tumors showed DACH1 promoter hyper-methylation. The studied micro-RNAs, expression was negatively correlated with DACH1 expression. The highest expressions of miRNAs and higher DACH1 promoter methylation were observed in advanced cancer situations. The Kaplan-Meier survival curves indicated that the overall survival was significantly poor in higher miRNAs and lower DACH1 expression in breast cancer patients (p<0.002). Conclusion: DACH1 down-regulation may be associated with a poor breast cancer prognosis. The DACH1 down-regulation may be due to epigenetic regulations such as promoter methylation, especially in triple-negative cases. Other factors, such as micro-RNAs (miR-217, miR-6807-3p, and miR-552), may also have an impact. The elevated expression of miR-217, miR-6807-3p, and miR-552, maybe candidates as possible poor prognostic biomarkers in breast cancer management for further consideration.