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环状 RNA 作为癌症的生物标志物和治疗靶点。

Circular RNAs as biomarkers and therapeutic targets in cancer.

机构信息

Bashkir State Medical University, Ufa, Republic of Bashkortostan, 450008, Russia.

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Institute of Brain Science, Harbin Medical University, Harbin, 150001, China.

出版信息

Semin Cancer Biol. 2022 Aug;83:242-252. doi: 10.1016/j.semcancer.2020.12.026. Epub 2021 Jan 9.

Abstract

Circular RNAs (circRNAs) are a class of single-stranded closed non-coding RNA molecules (ncRNAs), which are formed as a result of reverse splicing of mRNAs. Despite their relative abundance, an interest in understanding their regulatory importance is rather recent. High stability, abundance and evolutionary conservation among species underline some of their important traits. CircRNAs perform a variety of cellular functions ranging from miRNA and proteins sponges to transcriptional modulation and splicing. Additionally, most circRNAs are expressed aberrantly in pathological conditions suggesting their possible exploitation as diagnostic biomarkers. Their covalent closed cyclic structure resulting in resistance to RNases further makes them suitable as cancer biomarkers. Studies involving human tumors have verified differences in the expression profiles of circRNAs, indicating a regulatory role in cancer pathogenesis and metastasis. As endogenous competitive RNA, circRNAs can regulate tumor proliferation and invasion. Further, some circRNAs located in the nucleus can regulate transcription of genes by binding to RNA polymerase II. In this review, we elaborate the characteristics, functions and mechanisms of action of circRNAs in cancer. We also discuss the possibility of using circRNAs as potential therapeutic targets and biomarkers for cancer.

摘要

环状 RNA(circRNAs)是一类单链闭合的非编码 RNA 分子(ncRNAs),是由 mRNA 的反向剪接形成的。尽管它们的含量相对较高,但人们对其调节重要性的兴趣是最近才产生的。circRNAs 在物种间具有高度的稳定性、丰富度和进化保守性,这突显了它们的一些重要特征。circRNAs 具有多种细胞功能,从 miRNA 和蛋白质海绵到转录调控和剪接。此外,大多数 circRNAs 在病理条件下表达异常,表明它们可能作为诊断生物标志物被利用。circRNAs 的共价闭合环状结构使其对核糖核酸酶具有抗性,进一步使其成为癌症生物标志物的理想选择。涉及人类肿瘤的研究已经验证了 circRNAs 表达谱的差异,表明它们在癌症发病机制和转移中具有调节作用。作为内源性竞争性 RNA,circRNAs 可以通过调节肿瘤的增殖和侵袭来发挥作用。此外,一些位于核内的 circRNAs 可以通过与 RNA 聚合酶 II 结合来调节基因的转录。在这篇综述中,我们详细阐述了 circRNAs 在癌症中的特征、功能和作用机制。我们还讨论了将 circRNAs 作为癌症潜在治疗靶点和生物标志物的可能性。

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