药物诱导的 microRNAs 和长非编码 RNA 的修饰和调控，用于未来治疗多形性胶质母细胞瘤。

Drug-induced modifications and modulations of microRNAs and long non-coding RNAs for future therapy against Glioblastoma Multiforme.

机构信息

Laboratory of Functional Genomics and Disease Biology, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India.

出版信息

Gene. 2020 Jan 10;723:144126. doi: 10.1016/j.gene.2019.144126. Epub 2019 Oct 4.

DOI:10.1016/j.gene.2019.144126

PMID:31589963

Abstract

Non-coding RNAs are known to participate in cancer initiation, progression, and metastasis by regulating the status of chromatin epigenetics and gene expression. Although these non-coding RNAs do not possess defined protein-coding potential, they are involved in the expression and stability of messenger RNA (mRNA). The length of microRNAs (miRs) ranges between 20 and 22 nt, whereas, long non-coding RNAs (lncRNAs) length ranges between 200 nt to 1 Kb. In the case of circular RNAs (circRNAs), the size varies depending upon the length of the exon from where they were derived. Epigenetic regulations of miR and lncRNA genes will influence the gene expression by modulating histone acetylation and methylation patterns. Especially, lncRNAs will act as a scaffold for various epigenetic proteins, such as EZH2 and LSD1, and influence the chromatin epigenetic state at various genomic loci involved at silencing. Thus investigations on the expression of lncRNAs and designing drugs to modulate the expression of these genes will have a profound impact on future therapeutics against cancers such as Glioblastoma Multiforme (GBM) and also against various other diseases. With the recent advancements in genome-wide transcriptomic studies, scientists are focused on the non-coding RNAs and their regulations on various cellular processes involved in GBM and on other types of cancer as well as trying to understand possible epigenetic modulations that help in generating promising therapeutics for the future generations. In this review, the involvement of epigenetic proteins, enzymes that change chromatin architecture and epigenetic landscape and new roles of lncRNAs that are involved in GBM progression are elaborately discussed.

摘要

非编码 RNA 被认为通过调节染色质表观遗传学和基因表达状态参与癌症的发生、进展和转移。尽管这些非编码 RNA 不具有定义明确的蛋白质编码潜力，但它们参与信使 RNA（mRNA）的表达和稳定性。microRNAs（miRs）的长度在 20 到 22 个核苷酸之间，而长非编码 RNA（lncRNA）的长度在 200 个核苷酸到 1kb 之间。在环状 RNA（circRNA）的情况下，大小取决于它们衍生的外显子的长度。miR 和 lncRNA 基因的表观遗传调控通过调节组蛋白乙酰化和甲基化模式来影响基因表达。特别是，lncRNA 将作为各种表观遗传蛋白（如 EZH2 和 LSD1）的支架，并影响涉及沉默的各种基因组位点的染色质表观遗传状态。因此，对 lncRNA 表达的研究以及设计调节这些基因表达的药物将对未来针对胶质母细胞瘤（GBM）等癌症以及针对其他各种疾病的治疗产生深远影响。随着全基因组转录组研究的最新进展，科学家们专注于非编码 RNA 及其对 GBM 及其他类型癌症中涉及的各种细胞过程的调控，并试图了解可能的表观遗传调节，为未来的治疗提供有希望的治疗方法。在这篇综述中，详细讨论了表观遗传蛋白的参与、改变染色质结构和表观遗传景观的酶以及参与 GBM 进展的 lncRNA 的新作用。