University of Connecticut, Department of Pharmaceutical Sciences, 69 North Eagleville Road, Storrs, CT 06269, USA; University of Connecticut, Department of Molecular and Cell Biology, 91 North Eagleville Road, Storrs, CT 06269, USA; University of Connecticut, Institute for Systems Genomics, 181 Auditorium Road, Storrs, CT 06269, USA; University of Connecticut, UConn Stem Cell Institute, 400 Farmington Avenue Farmington, CT 06033, USA.
Semin Cancer Biol. 2019 Aug;57:36-44. doi: 10.1016/j.semcancer.2018.09.009. Epub 2018 Sep 28.
Cellular identity is established and maintained by the interplay of cell type-specific transcription factors and epigenetic regulation of the genome. During development in vivo and differentiation in vitro, transitions from one cell type to the next are triggered by cell signaling events culminating in modifications of chromatin that render genes accessible or inaccessible to the transcriptional apparatus. In recent years it has become apparent that cellular identity is plastic, and technological reprogramming methods such as somatic cell nuclear transfer and induced pluripotency can yield reprogrammed cells that have been restored to a state of developmental potency. Long noncoding RNAs (lncRNAs) are untranslated functional RNA molecules that are intimately involved in the regulation of the chromatin of protein-coding genes. In fact, recent evidence shows that there are more lncRNA species in the cell than mRNA species and that most protein-coding genes are likely to be under epigenetic regulation mediated by lncRNAs. This review examines lncRNA function in reprogrammed pluripotent cells and cancer stem cells. Because cancer stem cells arise from normal cells, their biogenesis can be viewed as a reprogramming process that occurs in vivo, and parallels between artificial reprogramming and cancer stem cell biogenesis are discussed.
细胞的身份是由细胞类型特异性转录因子的相互作用和基因组的表观遗传调控来建立和维持的。在体内发育和体外分化过程中，从一种细胞类型到另一种细胞类型的转变是由细胞信号事件引发的，最终导致染色质的修饰，使基因对转录装置可及或不可及。近年来，人们已经清楚地认识到细胞的身份是可塑的，体细胞细胞核转移和诱导多能性等技术重编程方法可以产生重新编程的细胞，这些细胞已经恢复到发育潜能的状态。长链非编码 RNA（lncRNA）是未翻译的功能性 RNA 分子，它们密切参与调节蛋白质编码基因的染色质。事实上，最近的证据表明，细胞中的 lncRNA 种类比 mRNA 种类多，而且大多数蛋白质编码基因可能受到 lncRNA 介导的表观遗传调控。这篇综述探讨了 lncRNA 在重编程多能细胞和癌症干细胞中的功能。因为癌症干细胞来源于正常细胞，它们的发生可以被视为体内发生的重编程过程，并且讨论了人工重编程和癌症干细胞发生之间的相似性。
