DeSouza Patrick A, Qu Xuan, Chen Hao, Patel Bhuvic, Maher Christopher A, Kim Albert H
Department of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Cancers (Basel). 2021 Mar 31;13(7):1604. doi: 10.3390/cancers13071604.
Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs. Of these transcripts, the majority-long, noncoding RNAs (lncRNAs)-are greater than 200 nucleotides in length and are necessary for various roles in the cell. It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs. Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging. The cooperation between genetic and epigenetic alterations drives rapid adaptation that allows therapeutic evasion and recurrence. Given the large repertoire of lncRNAs in normal brain tissue and the well-described roles of lncRNAs in molecular and cellular processes, these transcripts are important to consider in the context of GBM heterogeneity and treatment resistance. Herein, we review the general mechanisms and biological roles of lncRNAs, with a focus on GBM, as well as RNA-based therapeutics currently in development.
转录发生在超过70%的人类基因组上,目前注释的基因中有超过一半会产生功能性非编码RNA。在这些转录本中,大多数——长链非编码RNA(lncRNA)——长度超过200个核苷酸,并且在细胞中发挥各种作用是必需的。人们越来越认识到这些lncRNA在健康和疾病状态中都具有相关性,与其他器官相比,大脑中表达的lncRNA数量最多。胶质母细胞瘤(GBM)是一种侵袭性致命脑肿瘤,表现出显著的肿瘤内异质性,这使得开发有效的治疗方法具有挑战性。基因和表观遗传改变之间的协同作用驱动了快速适应,从而实现治疗逃逸和复发。鉴于正常脑组织中lncRNA种类繁多,以及lncRNA在分子和细胞过程中的明确作用,在GBM异质性和治疗耐药性的背景下,这些转录本值得关注。在此,我们综述lncRNA的一般机制和生物学作用,重点关注GBM,以及目前正在开发的基于RNA的疗法。