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 NasirpourMohammad HosseinSalimiMahdiehDiagnostic Laboratory Sciences and Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Student Research Committee, Shiraz University of Medical Sciences, Shiraz, IranMajidiFaezehMinuchehrZarrinGenetic Research Center, University of Social Welfare and Rehabilitation Science, Tehran, IranMozdaraniHosseinMonoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran 15 2 108 117 15 10 2022 22 2 2023

<p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Background:</span></strong><span style="font-size:10.0pt"> 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<strong>.</strong><strong> </strong>Herein, the expression of&nbsp;<em>DACH1</em>&nbsp;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 <em>DACH1</em>, was assessed.&nbsp; </span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Methods:</span></strong> <span style="font-size:10.0pt">The SYBR green-based Real-Time reverse transcription-PCR was used to determine&nbsp;<em>DACH1</em>&nbsp;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&nbsp;<em>DACH1</em>&nbsp;was investigated using the </span><span style="font-size:10.0pt">Methylation-specific PCR<em> </em></span><span style="font-size:10.0pt">technique. </span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Results: </span></strong><em><span style="font-size:10.0pt">DACH1</span></em><span style="font-size:10.0pt">&nbsp;expression was significantly down-regulated in breast tumors (p&lt; 0.05). About 33.5% of tumors showed&nbsp;<em>DACH1</em>&nbsp;promoter hyper-methylation. The studied micro-RNAs, expression was negatively correlated with <em>DACH1</em> expression. The highest expressions of miRNAs and higher&nbsp;<em>DACH1</em>&nbsp;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 <em>DACH1</em> expression in breast cancer patients (p&lt;0.002).</span></span></p> <p><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Conclusion:</span></strong><em><span style="font-size:10.0pt"> DACH1</span></em><span style="font-size:10.0pt">&nbsp;down-regulation may be associated with a poor breast cancer prognosis. The&nbsp;<em>DACH1</em> 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 </span><span style="font-size:10.0pt">impact. The elevated expression of </span><span style="font-size:10.0pt">miR-217, miR-6807-3p, and miR-552, maybe candidates as possible poor prognostic biomarkers in breast cancer management for further consideration.</span></span></p>