Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, P.R. China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of The University of South China, Hengyang, Hunan, 421001, P.R. China.
Mol Cancer. 2021 Feb 3;20(1):26. doi: 10.1186/s12943-021-01318-6.
Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.
结直肠癌（CRC）是一种常见的遗传性肿瘤，通常具有致命性。其发病机制涉及多个基因，包括环状 RNA（circRNA）。值得注意的是，circRNA 构成了一类新型的非编码 RNA（ncRNA），具有共价闭合环结构，被认为是在真核生物中以组织/发育特异性模式大量表达的稳定、保守分子。基于不断积累的证据，CRC 组织、细胞、外泌体和 CRC 患者的血液中存在 circRNA 的异常表达。此外，许多 circRNA 已被鉴定为癌基因或肿瘤抑制因子，可介导 CRC 中的肿瘤发生、转移和化学放射抵抗。尽管 circRNA 生物发生和功能的调节机制仍相当难以捉摸，但在研究 CRC 时已获得有趣的结果。特别是，circRNA 在 CRC 中的表达受到多种因素的综合调控，如剪接因子、转录因子、特定酶和顺式作用元件。更重要的是，circRNA 通过多种机制对 CRC 发挥关键作用，包括充当 miRNA 海绵或诱饵、与 RNA 结合蛋白相互作用，甚至翻译功能性肽。最后，circRNA 可能作为有前途的诊断和预后生物标志物以及 CRC 临床实践中的潜在治疗靶点。在本综述中，我们讨论了 circRNA 在 CRC 中的失调、功能和临床意义，并进一步讨论了 circRNA 发挥功能的分子机制及其表达如何受到调控。基于本综述，我们希望揭示 circRNA 在癌症发生和进展中的功能，并强调靶向 circRNA 在癌症研究中的未来策略。
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