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环状RNA作为癌症新兴生物标志物和潜在治疗靶点的生物学作用及调控

Biological role and regulation of circular RNA as an emerging biomarker and potential therapeutic target for cancer.

作者信息

Saleem Ayman, Khan Muhammad Umer, Zahid Tazeen, Khurram Iqra, Ghani Muhammad Usman, Ullah Inam, Munir Rakhtasha, Calina Daniela, Sharifi-Rad Javad

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.

Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan.

出版信息

Mol Biol Rep. 2024 Feb 10;51(1):296. doi: 10.1007/s11033-024-09211-3.

DOI:10.1007/s11033-024-09211-3
PMID:38340202
Abstract

Circular RNAs (circRNAs) are a unique family of endogenous RNAs devoid of 3' poly-A tails and 5' end caps. These single-stranded circRNAs, found in the cytoplasm, are synthesized via back-splicing mechanisms, merging introns, exons, or both, resulting in covalently closed circular loops. They are profusely expressed across the eukaryotic transcriptome and offer heightened stability against exonuclease RNase R compared to linear RNA counterparts. This review endeavors to provide a comprehensive overview of circRNAs' characteristics, biogenesis, and mechanisms of action. Furthermore, aimed to shed light on the potential of circRNAs as significant biomarkers in various cancer types. It has been performed an exhaustive literature review, drawing on recent studies and findings related to circRNA characteristics, synthesis, function, evaluation techniques, and their associations with oncogenesis. CircRNAs are intricately associated with tumor progression and development. Their multifaceted roles encompass gene regulation through the sponging of proteins and microRNAs, controlling transcription and splicing, interacting with RNA binding proteins (RBPs), and facilitating gene translation. Due to these varied roles, circRNAs have become a focal point in tumor pathology investigations, given their promising potential as both biomarkers and therapeutic agents. CircRNAs, due to their unique biogenesis and multifunctionality, hold immense promise in the realm of oncology. Their stability, widespread expression, and intricate involvement in gene regulation underscore their prospective utility as reliable biomarkers and therapeutic targets in cancer. As our understanding of circRNAs deepens, advanced techniques for their detection, evaluation, and manipulation will likely emerge. These advancements might catalyze the translation of circRNA-based diagnostics and therapeutics into clinical practice, potentially revolutionizing cancer care and prognosis.

摘要

环状RNA(circRNAs)是一类独特的内源性RNA,没有3'多聚腺苷尾巴和5'端帽。这些存在于细胞质中的单链circRNAs是通过反向剪接机制合成的,将内含子、外显子或两者合并,形成共价闭合的环状结构。它们在真核转录组中大量表达,与线性RNA相比,对核酸外切酶RNase R具有更高的稳定性。本综述旨在全面概述circRNAs的特征、生物发生和作用机制。此外,旨在阐明circRNAs作为各种癌症类型中重要生物标志物的潜力。我们进行了详尽的文献综述,借鉴了与circRNA特征、合成、功能、评估技术及其与肿瘤发生的关联相关的最新研究和发现。CircRNAs与肿瘤进展和发展密切相关。它们的多方面作用包括通过与蛋白质和微小RNA结合来调控基因、控制转录和剪接、与RNA结合蛋白(RBPs)相互作用以及促进基因翻译。由于这些多样的作用,circRNAs因其作为生物标志物和治疗剂的潜在前景,已成为肿瘤病理学研究的焦点。CircRNAs由于其独特的生物发生和多功能性,在肿瘤学领域具有巨大的潜力。它们的稳定性、广泛表达以及在基因调控中的复杂参与突出了它们作为癌症中可靠生物标志物和治疗靶点的潜在效用。随着我们对circRNAs的理解不断加深,可能会出现用于其检测、评估和操作的先进技术。这些进展可能会促使基于circRNA的诊断和治疗方法转化为临床实践,有可能彻底改变癌症治疗和预后。

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Int J Mol Sci. 2025 May 19;26(10):4842. doi: 10.3390/ijms26104842.
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