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

Abstract

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. 

Dachshund Homolog 1: Unveiling Its Potential Role in Megakaryopoiesis and Bacillus anthracis Lethal Toxin-Induced Thrombocytopenia

“…The DACH1 gene has been extensively studied and recognized as a crucial transcription regulator for the development of various organs and tissue, including the eyes, legs, nervous system, arterial vessels, and female reproductive tract in humans, mice, and Drosophila [ 52 , 53 , 54 , 55 , 75 , 76 , 77 ]. Furthermore, DACH1 has been recognized as a tumor suppressor gene in humans [ 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. Despite its extensive study, limited research directly explored its role in hematopoiesis, with only two notable studies.…”

“…Low expression of DACH1 has been observed in various types of tumors, such as breast tumors, esophageal cancer, lung cancer, and endometrial cancer. This low expression is correlated with increased tumor proliferation, metastasis, tumor mutation burden, reduced prognostic survival, radio sensitivity, and chemotherapy sensitivity [ 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. Furthermore, high methylation of the DACH1 promoter results in reduced expression of DACH1 in tumors [ 62 , 63 ].…”

“…This low expression is correlated with increased tumor proliferation, metastasis, tumor mutation burden, reduced prognostic survival, radio sensitivity, and chemotherapy sensitivity [ 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. Furthermore, high methylation of the DACH1 promoter results in reduced expression of DACH1 in tumors [ 62 , 63 ]. While the functional role of DACH1 in megakaryopoiesis remains unknown, earlier studies have suggested its involvement in myeloid commitment [ 64 ].…”

Cuproptosis-related prognostic signatures predict the prognosis and immunotherapy in HCC patients

“…In recent years, an increasing number of studies have shown that genes and lncRNAs expression may be related to tumorigenesis and the progression of tumors, suggesting that genes and lncRNAs are expected to be novel biomarkers and therapeutic targets. [11][12][13][14][15] Cuproptosis is a unique proteotoxic cell death pathway in which copper binds directly to the lipoylated proteins of the tricarboxylic acid cycle cycle. [5] However, the expression and roles of CRGs and lncRNAs in HCC remain unclear.…”

Epigenetic targets to enhance antitumor immune response through the induction of tertiary lymphoid structures

“…The expression of PNAd on the endothelial cells of HEVs was found to be regulated by the TF, DACH1 ( 181 ). DACH1 downregulation due to hypermethylation at its promoter region enhanced the growth and progression of gastric, colorectal, breast, and hepatocellular carcinoma ( 182 – 185 ). Specific demethylating agents at the DACH1 promoter region could stimulate its expression, activating PNAd expression and HEV formation.…”