肾癌干细胞与表观遗传学调控研究进展

Kidney cancer stem cells and epigenetic regulation

针对肿瘤干细胞进行靶向治疗是遏止肿瘤复发和转移的关键。表观遗传学在干细胞发育及体细胞重编程中的重要作用提示其可能在肿瘤干细胞的发生发展中发挥作用。表观基因组包含DNA甲基化、组蛋白修饰、染色体重塑和非编码RNA调控的基因表达模式,在肾癌细胞中有多种表观基因组的异常改变。目前已成功的从肾细胞癌中获得SP细胞、细胞囊球和CD105+细胞等具肿瘤干细胞属性的细胞亚群。随着对肾细胞癌(renal cell carcinoma,RCC)遗传研究的不断深入,发现DNA序列以外的调控机制异常在肿瘤的发生发展过程中起重要的作用。对肾癌发生相关的表观遗传学的认识有助于推进新的治疗方式,而对发现新的预后和早期诊断标志将起更重要的作用。本文对目前肾癌干细胞和表观遗传学相关领域的最新研究,特别是肾癌干细胞发生和发展过程中表观遗传学可能的调控作用及机制进行综述。

Targeted therapeutic strategy for cancer stem cells （CSCs） is the key to prevent tumor relapse and metastasis. The im-portant roles of epigenetic regulation on the development of stem cells and gene reprogram of somatic cells suggest that this process may remarkably affect the occurrence and development of CSCs. The epigenome, which comprises DNA methylation, histone modifica-tions, chromatin structures, and non-coding RNAs, controls gene expression patterns. In renal cell carcinoma （RCC）, aberrant changes occur in the epigenome. To date, cells with CSC properties from RCC have been successfully isolated using different methods, such as sorting using the Hoechst 33342 side population, forming tumor spheroid, and sorting CD105 cell surface biomarker. According to the progress in genetic studies on RCC, in addition to DNA sequence, the abnormality in the regulatory mechanism has considerable func-tions in tumor progression. Epigenetic changes may be integral to the behavior of cancer progenitor cells and their progeny. Knowledge on epigenetics in renal tumorigenesis process is beneficial in the development of new therapeutic modalities and may deliver new prog-nostic and early diagnostic markers. This paper reviews the latest development in the study of RCC stem cells and the underlying mech-anisms of epigenetic regulation on the development of CSCs in RCC.