Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.
Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.
Prog Mol Biol Transl Sci. 2023;197:241-260. doi: 10.1016/bs.pmbts.2023.01.010. Epub 2023 Mar 2.
The cells of multicellular organisms are genetically homogeneous but heterogenous in structure and function by virtue of differential gene expression. During embryonic development, differential gene expression by modification of chromatin (DNA and histone complex) regulates the developmental proceedings before and after the germ layers are formed. Post-replicative DNA modification, where the fifth carbon atom of the cytosine gets methylated (hereafter, DNA methylation), does not incorporate mutations within the DNA. In the past few years, a boom has been observed in the field of research related to various epigenetic regulation models, which includes DNA methylation, post-translational modification of histone tails, control of chromatin structure by non-coding RNAs, and remodeling of nucleosome. Epigenetic effects like DNA methylation or histone modification play a cardinal role in development but also be able to arise stochastically, as observed during aging, in tumor development and cancer progression. Over the past few decades, researchers allured toward the involvement of pluripotency inducer genes in cancer progression and apparent for prostate cancer (PCa); also, PCa is the most diagnosed tumor worldwide and comes to the second position in causing mortality in men. The anomalous articulation of pluripotency-inducing transcription factor; SRY-related HMG box-containing transcription factor-2 (SOX2), Octamer-binding transcription factor 4 (OCT4) or POU domain, class 5, transcription factor 1 (POU5F1), and NANOG have been reported in different cancers which includes breast cancer, tongue cancer, and lung cancer, etc. Although there is a variety in gene expression signatures demonstrated by cancer cells, the epigenetic mode of regulation at the pluripotency-associated genes in PCa has been recently explored. This chapter focuses on the epigenetic control of NANOG and SOX2 genes in human PCa and the precise role thereof executed by the two transcription factors.
多细胞生物的细胞在遗传上是同质的，但由于基因表达的差异，在结构和功能上是异质的。在胚胎发育过程中，染色质（DNA 和组蛋白复合物）的修饰通过差异基因表达来调节原肠胚形成前后的发育过程。复制后 DNA 修饰，即胞嘧啶的第五个碳原子被甲基化（以下简称 DNA 甲基化），不会在 DNA 内引入突变。在过去的几年中，与各种表观遗传调控模型相关的研究领域取得了蓬勃发展，其中包括 DNA 甲基化、组蛋白尾部的翻译后修饰、非编码 RNA 对染色质结构的控制以及核小体的重塑。表观遗传效应，如 DNA 甲基化或组蛋白修饰，在发育中起着至关重要的作用，但也可以随机出现，如在衰老、肿瘤发生和癌症进展中观察到的那样。在过去的几十年中，研究人员被吸引到多能诱导基因在癌症进展中的参与，这在前列腺癌（PCa）中表现明显；此外，PCa 是全球最常见的诊断肿瘤，在导致男性死亡方面排名第二。多能诱导转录因子的异常表达；Sry 相关 HMG 盒结合转录因子-2（SOX2）、八聚体结合转录因子 4（OCT4）或 POU 域、类 5、转录因子 1（POU5F1）和 NANOG 已在不同癌症中报道，包括乳腺癌、舌癌和肺癌等。尽管癌细胞表现出多种基因表达特征，但最近已经探索了 PCa 中与多能性相关基因的表观遗传调控模式。本章重点介绍了 NANOG 和 SOX2 基因在人类 PCa 中的表观遗传调控及其两个转录因子所执行的精确作用。
