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非编码RNA作为恶性肿瘤表观遗传变化的介导因子

Non-Coding RNAs as Mediators of Epigenetic Changes in Malignancies.

作者信息

Kumar Subhasree, Gonzalez Edward A, Rameshwar Pranela, Etchegaray Jean-Pierre

机构信息

Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.

Department of Medicine, Hematology/Oncology, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USA.

出版信息

Cancers (Basel). 2020 Dec 5;12(12):3657. doi: 10.3390/cancers12123657.

Abstract

Non-coding RNAs (ncRNAs) are untranslated RNA molecules that regulate gene expressions. NcRNAs include small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), circular RNAs (cRNAs) and piwi-interacting RNAs (piRNAs). This review focuses on two types of ncRNAs: microRNAs (miRNAs) or short interfering RNAs (siRNAs) and long non-coding RNAs (lncRNAs). We highlight the mechanisms by which miRNAs and lncRNAs impact the epigenome in the context of cancer. Both miRNAs and lncRNAs have the ability to interact with numerous epigenetic modifiers and transcription factors to influence gene expression. The aberrant expression of these ncRNAs is associated with the development and progression of tumors. The primary reason for their deregulated expression can be attributed to epigenetic alterations. Epigenetic alterations can cause the misregulation of ncRNAs. The experimental evidence indicated that most abnormally expressed ncRNAs impact cellular proliferation and apoptotic pathways, and such changes are cancer-dependent. In vitro and in vivo experiments show that, depending on the cancer type, either the upregulation or downregulation of ncRNAs can prevent the proliferation and progression of cancer. Therefore, a better understanding on how ncRNAs impact tumorigenesis could serve to develop new therapeutic treatments. Here, we review the involvement of ncRNAs in cancer epigenetics and highlight their use in clinical therapy.

摘要

非编码RNA(ncRNAs)是一类可调控基因表达的未翻译RNA分子。ncRNAs包括小核RNA(snRNAs)、小核仁RNA(snoRNAs)、核糖体RNA(rRNAs)、转运RNA(tRNAs)、环状RNA(cRNAs)和piwi相互作用RNA(piRNAs)。本综述聚焦于两类ncRNAs:微小RNA(miRNAs)或小干扰RNA(siRNAs)以及长链非编码RNA(lncRNAs)。我们着重介绍了miRNAs和lncRNAs在癌症背景下影响表观基因组的机制。miRNAs和lncRNAs均有能力与众多表观遗传修饰因子和转录因子相互作用,从而影响基因表达。这些ncRNAs的异常表达与肿瘤的发生和发展相关。其表达失调的主要原因可归因于表观遗传改变。表观遗传改变可导致ncRNAs的调控异常。实验证据表明,大多数异常表达的ncRNAs会影响细胞增殖和凋亡途径,且这种变化具有癌症依赖性。体外和体内实验表明,根据癌症类型的不同,ncRNAs的上调或下调均可抑制癌症的增殖和进展。因此,更好地理解ncRNAs如何影响肿瘤发生有助于开发新的治疗方法。在此,我们综述了ncRNAs在癌症表观遗传学中的作用,并强调了它们在临床治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba26/7762117/6809dcc6b077/cancers-12-03657-g001.jpg

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