Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
Department of Traditional Chinese Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
J Exp Clin Cancer Res. 2021 Jan 6;40(1):11. doi: 10.1186/s13046-020-01798-2.
AS (alternative splicing) is a fundamental process by which a gene can generate multiple distinct mRNA transcripts to increase protein diversity. Defects in AS influence the occurrence and development of many diseases, including cancers, and are frequently found to participate in various aspects of cancer biology, such as promoting invasion, metastasis, apoptosis resistance and drug resistance. NcRNAs (noncoding RNAs) are an abundant class of RNAs that do not encode proteins. NcRNAs include miRNAs (microRNAs), lncRNAs (long noncoding RNAs), circRNAs (circular RNAs) and snRNAs (small nuclear RNAs) and have been proven to act as regulatory molecules that mediate cancer processes through AS. NcRNAs can directly or indirectly influence a plethora of molecular targets to regulate cis-acting elements, trans-acting factors, or pre-mRNA transcription at multiple levels, affecting the AS process and generating alternatively spliced isoforms. Consequently, ncRNA-mediated AS outcomes affect multiple cellular signaling pathways that promote or suppress cancer progression. In this review, we summarize the current mechanisms by which ncRNAs regulate AS in cancers and discuss their potential clinical applications as biomarkers and therapeutic targets.
可变剪接（AS）是基因产生多种不同 mRNA 转录本以增加蛋白质多样性的一种基本过程。AS 的缺陷会影响许多疾病的发生和发展，包括癌症，并且经常发现其参与癌症生物学的各个方面，如促进侵袭、转移、抗凋亡和耐药性。ncRNAs（非编码 RNA）是一类丰富的不编码蛋白质的 RNA。ncRNAs 包括 miRNAs（microRNAs）、lncRNAs（长非编码 RNA）、circRNAs（环状 RNA）和 snRNAs（小核 RNA），已被证明作为调节分子通过 AS 介导癌症过程。ncRNAs 可以直接或间接地影响众多分子靶标，以在多个水平上调节顺式作用元件、反式作用因子或前体 mRNA 转录，影响 AS 过程并产生可变剪接异构体。因此，ncRNA 介导的 AS 结果会影响促进或抑制癌症进展的多种细胞信号通路。在这篇综述中，我们总结了 ncRNAs 在癌症中调节 AS 的现有机制，并讨论了它们作为生物标志物和治疗靶点的潜在临床应用。
