Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India.
Department of Radiology, AIIMS, Bathinda, 151001, India.
Med Oncol. 2022 Aug 16;39(11):171. doi: 10.1007/s12032-022-01770-4.
Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs' role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review.
遗传异常，包括癌基因和肿瘤抑制基因的突变，将正常细胞转化为肿瘤细胞。表观遗传修饰与遗传因素共同作用，控制癌症的发生。组蛋白乙酰转移酶（HATs）、组蛋白去乙酰化酶（HDACs）、DNA 甲基转移酶（DNMTs）和染色质结构修饰因子是潜在的表观遗传调控因子。具体而言，HDACs 是调节细胞存活、生长、凋亡和代谢相关基因表达的组蛋白修饰酶。大多数 HDACs 在癌症中高度上调，而有些在癌症进展中具有不同的功能和表达。不同的 HDACs 在控制癌症进展中具有正反两方面的作用。HDACs 还显著参与肿瘤细胞获得转移和血管生成潜能，以耐受抗肿瘤微环境。HDACs 在调节代谢基因中的作用也与肿瘤的发生和存活有关。本文综述了 HDACs 通过调节细胞存活、凋亡、转移、侵袭、干性、血管生成和上皮间质转化（EMT）来调控肿瘤细胞的分子机制，并对其进行了讨论。HDACs 是抗癌药物开发的潜在靶点，已经开发出多种抑制剂并获得 FDA 批准用于多种癌症。本文还重点介绍了具有明确抗癌疗效的主要 HDAC 抑制剂。
