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DACH1表达及其表观遗传调控因子作为潜在乳腺癌相关生物标志物的研究。

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

作者信息

Nasirpour Mohammad Hossein, Salimi Mahdieh, Majidi Faezeh, Minuchehr Zarrin, Mozdarani Hossein

机构信息

Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

出版信息

Avicenna J Med Biotechnol. 2023 Apr-Jun;15(2):108-117.

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 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 , was assessed.

METHODS

The SYBR green-based Real-Time reverse transcription-PCR was used to determine 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 was investigated using the Methylation-specific PCR technique.

RESULTS

expression was significantly down-regulated in breast tumors (p<0.05). About 33.5% of tumors showed promoter hyper-methylation. The studied micro-RNAs, expression was negatively correlated with expression. The highest expressions of miRNAs and higher 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 expression in breast cancer patients (p<0.002).

CONCLUSION

down-regulation may be associated with a poor breast cancer prognosis. The 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.

摘要

背景

乳腺癌发生涉及遗传和表观遗传变化。DNA甲基化以及微小RNA调控是乳腺癌中失调的重要表观遗传现象。在此,分析了作为肿瘤抑制基因的[具体基因名称未给出]的表达及其启动子甲基化状态。此外,评估了先前报道靶向[具体基因名称未给出]的三种微小RNA(miR - 217、miR - 6807 - 3p和miR - 552)的表达。

方法

采用基于SYBR Green的实时逆转录PCR法,与标准对照相比,测定120例乳腺导管癌肿瘤中[具体基因名称未给出]和微小RNA(miR - 217、miR - 6807 - 3p和miR - 552)的表达。此外,使用甲基化特异性PCR技术研究[具体基因名称未给出]的启动子甲基化模式。

结果

[具体基因名称未给出]在乳腺肿瘤中的表达显著下调(p<0.05)。约33.5%的肿瘤显示[具体基因名称未给出]启动子高甲基化。所研究的微小RNA的表达与[具体基因名称未给出]的表达呈负相关。在晚期癌症情况下观察到微小RNA的最高表达和较高的[具体基因名称未给出]启动子甲基化。Kaplan - Meier生存曲线表明,乳腺癌患者中微小RNA表达较高且[具体基因名称未给出]表达较低时,总生存期显著较差(p<0.002)。

结论

[具体基因名称未给出]下调可能与乳腺癌预后不良有关。[具体基因名称未给出]下调可能归因于启动子甲基化等表观遗传调控,尤其是在三阴性病例中。其他因素,如微小RNA(miR - 217、miR - 6807 - 3p和miR - 552),也可能有影响。miR - 217、miR - 6807 - 3p和miR - 552的表达升高,可能作为乳腺癌管理中可能的不良预后生物标志物以供进一步考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57e9/10073918/4a7e5408e20d/AJMB-15-108-g001.jpg

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