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宫颈癌中的组蛋白修饰:表观遗传机制、功能及临床意义(综述)

Histone modifications in cervical cancer: Epigenetic mechanisms, functions and clinical implications (Review).

作者信息

Li Xuewei, Zhou Min, Yu Jing, Yu Shaohui, Ruan Zheng

机构信息

Department of Gynecology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.

Department of Endocrinology, The Affiliated Hospital of Changchun University to Chinese Medicine, Changchun, Jilin 130021, P.R. China.

出版信息

Oncol Rep. 2025 Oct;54(4). doi: 10.3892/or.2025.8964. Epub 2025 Aug 8.

Abstract

Cervical cancer (CC) poses a substantial global health challenge and it ranks as the fourth most prevalent malignancy among women worldwide. Management strategies include surgical intervention, radiotherapy, chemotherapy and emerging systemic treatments. Although advancements in immunotherapy and targeted therapies have been achieved, the aggressive metastatic nature of the disease, coupled with immune evasion and drug resistance, continues to limit overall survival rates. Therefore, there remains an urgent need to identify novel treatment modalities and more effective therapeutic agents. As fundamental regulators of epigenetic modifications, histone alterations serve a critical role in controlling gene expression, DNA repair mechanisms and cellular differentiation. These modifications include acetylation, methylation, phosphorylation, ubiquitination, ADP‑ribosylation and glycosylation, as well as the more recently identified lactylation and palmitoylation. By restructuring chromatin and facilitating interactions among histones, DNA and regulatory proteins, these modifications exert a substantial influence on cellular functions. Aberrant histone modifications contribute to tumorigenesis, tumor heterogeneity and resistance to conventional anticancer therapies, making them a key focus of oncological research. In recent years, therapeutic strategies targeting histone modifications have gained increasing attention in the treatment of CC. Among these epigenetic alterations, histone acetylation and deacetylation have been extensively studied, with numerous histone deacetylase inhibitors showing promise in preclinical studies. The present review explores the patterns of histone modifications in CC, emphasizing their molecular roles in tumor progression, metastasis and therapeutic resistance. Additionally, histone modification‑driven therapeutic targets are examined, laying the groundwork for future precision medicine approaches in CC treatment.

摘要

宫颈癌(CC)是一项重大的全球健康挑战,在全球女性中它是第四大最常见的恶性肿瘤。治疗策略包括手术干预、放疗、化疗以及新兴的全身治疗。尽管免疫疗法和靶向疗法已取得进展,但该疾病具有侵袭性转移的特性,再加上免疫逃逸和耐药性,持续限制着总体生存率。因此,迫切需要确定新的治疗方式和更有效的治疗药物。作为表观遗传修饰的基本调节因子,组蛋白改变在控制基因表达、DNA修复机制和细胞分化中起着关键作用。这些修饰包括乙酰化、甲基化、磷酸化、泛素化、ADP-核糖基化和糖基化,以及最近发现的乳酰化和棕榈酰化。通过重塑染色质并促进组蛋白、DNA和调节蛋白之间的相互作用,这些修饰对细胞功能产生重大影响。异常的组蛋白修饰有助于肿瘤发生、肿瘤异质性以及对传统抗癌疗法的耐药性,使其成为肿瘤学研究的关键焦点。近年来,针对组蛋白修饰的治疗策略在宫颈癌治疗中受到越来越多的关注。在这些表观遗传改变中,组蛋白乙酰化和去乙酰化已得到广泛研究,众多组蛋白去乙酰化酶抑制剂在临床前研究中显示出前景。本综述探讨了宫颈癌中组蛋白修饰的模式,强调它们在肿瘤进展、转移和治疗耐药性中的分子作用。此外,还研究了由组蛋白修饰驱动的治疗靶点,为未来宫颈癌治疗的精准医学方法奠定基础。

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