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DNA去甲基化中间体“5-羟甲基胞嘧啶”在卵巢癌治疗中的作用:综述

Role of DNA De-methylation intermediate '5-hydroxymethylcytosine' in ovarian cancer management: A comprehensive review.

作者信息

Bisht Deepa, Arora Arisha, Sachan Manisha

机构信息

Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Prayagraj 211004, Uttar Pradesh, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, 781039 Assam, India.

出版信息

Biomed Pharmacother. 2022 Nov;155:113674. doi: 10.1016/j.biopha.2022.113674. Epub 2022 Sep 12.

Abstract

Ovarian cancer remains the most eminent silent killer, with high morbidity and mortality among all gynaecological cancers. The advanced-stage patient's diagnosis has a low survival rate caused by its asymptomatic progression and diverse histopathological sub-types, wherefore in poor prognosis and highly recurring malignancy with multidrug resistance towards chemotherapy. Epigenetic biomarkers open promising avenues of intriguing research to combat OC malignancy, furthermore a tool for its early diagnosis. 5-hydroxymethycytosine (5-hmC), alias the sixth base of the genome, is an intermediate formed during the recently established DNA demethylation process and catalysed via ten-eleven translocation (TET) family of enzymes. It plays a significant role in regulating gene expression and has sparked interest in various cancer types. This review summarizes the role of active DNA demethylation process, its enzymes and intermediate 5-hmC in epigenetic landscape of ovarian cancer as a potent biomarker for clinical translation in identification of therapeutic targets, diagnostic and prognostic evaluation.

摘要

卵巢癌仍然是最危险的隐匿性杀手,在所有妇科癌症中发病率和死亡率都很高。晚期患者由于其无症状进展和多样的组织病理学亚型,诊断后的生存率较低,因此预后较差,且是具有多药耐药性的高复发性恶性肿瘤。表观遗传生物标志物为对抗卵巢癌恶性肿瘤开辟了有趣的研究途径,也是早期诊断的工具。5-羟甲基胞嘧啶(5-hmC),别名基因组的第六碱基,是最近建立的DNA去甲基化过程中形成的中间体,由十一-易位(TET)家族的酶催化。它在调节基因表达中起重要作用,并引发了对各种癌症类型的关注。本综述总结了活性DNA去甲基化过程、其酶和中间体5-hmC在卵巢癌表观遗传格局中的作用,作为一种有效的生物标志物用于临床转化,以识别治疗靶点、进行诊断和预后评估。

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