Li Zeru, Zhao Bangbo, Qin Cheng, Wang Yuanyang, Li Tianhao, Wang Weibin
Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2022 Jul 29;12:935877. doi: 10.3389/fonc.2022.935877. eCollection 2022.
Digestive system tumors have a poor prognosis due to complex anatomy, insidious onset, challenges in early diagnosis, and chemoresistance. Epidemiological statistics has verified that digestive system tumors rank first in tumor-related death. Although a great number of studies are devoted to the molecular biological mechanism, early diagnostic markers, and application of new targeted drugs in digestive system tumors, the therapeutic effect is still not satisfactory. Epigenomic alterations including histone modification and chromatin remodeling are present in human cancers and are now known to cooperate with genetic changes to drive the cancer phenotype. Chromatin is the carrier of genetic information and consists of DNA, histones, non-histone proteins, and a small amount of RNA. Chromatin and nucleosomes control the stability of the eukaryotic genome and regulate DNA processes such as transcription, replication, and repair. The dynamic structure of chromatin plays a key role in this regulatory function. Structural fluctuations expose internal DNA and thus provide access to the nuclear machinery. The dynamic changes are affected by various complexes and epigenetic modifications. Variation of chromatin dynamics produces early and superior regulation of the expression of related genes and downstream pathways, thereby controlling tumor development. Intervention at the chromatin level can change the process of cancer earlier and is a feasible option for future tumor diagnosis and treatment. In this review, we introduced chromatin dynamics including chromatin remodeling, histone modifications, and chromatin accessibility, and current research on chromatin regulation in digestive system tumors was also summarized.
由于解剖结构复杂、发病隐匿、早期诊断困难以及存在化疗耐药性，消化系统肿瘤的预后较差。流行病学统计证实，消化系统肿瘤在肿瘤相关死亡中位居首位。尽管大量研究致力于消化系统肿瘤的分子生物学机制、早期诊断标志物以及新型靶向药物的应用，但其治疗效果仍不尽人意。包括组蛋白修饰和染色质重塑在内的表观基因组改变存在于人类癌症中，并且已知与基因变化协同作用以驱动癌症表型。染色质是遗传信息的载体，由DNA、组蛋白、非组蛋白和少量RNA组成。染色质和核小体控制真核基因组的稳定性，并调节DNA的转录、复制和修复等过程。染色质的动态结构在这种调节功能中起关键作用。结构波动会暴露内部DNA，从而为核机制提供作用途径。动态变化受各种复合物和表观遗传修饰的影响。染色质动力学的变化对相关基因和下游通路的表达产生早期且卓越的调控，进而控制肿瘤发展。在染色质水平进行干预可以更早地改变癌症进程，是未来肿瘤诊断和治疗的一个可行选择。在本综述中，我们介绍了包括染色质重塑、组蛋白修饰和染色质可及性在内的染色质动力学，并总结了目前关于消化系统肿瘤中染色质调控的研究。
