Noncoding RNAs regulate alternative splicing in Cancer.
Noncoding RNAs regulate alternative splicing in Cancer.
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DOI：
10.1186/s13046-020-01798-2
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发表时间：
2021-01-06
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu Y;Liu X;Lin C;Jia X;Zhu H;Song J;Zhang Y
选择性剪接（alternative splicing，AS）是基因产生多种mRNA转录本以增加蛋白质多样性的基本过程。AS的缺陷影响包括癌症在内的许多疾病的发生和发展，并且经常被发现参与癌症生物学的各个方面，例如促进侵袭、转移、凋亡抗性和耐药性。非编码RNA（non coding RNA）是一类不编码蛋白质的RNA。NcRNA包括miRNA（microRNA）、lncRNA（长链非编码RNA）、circRNA（环状RNA）和snRNA（小核RNA），并且已被证明作为调节分子通过AS介导癌症过程。NcRNA可以直接或间接地影响大量的分子靶点，以在多个水平上调节顺式作用元件、反式作用因子或前mRNA转录，从而影响AS过程并产生选择性剪接异构体。因此，ncRNA介导的AS结果影响促进或抑制癌症进展的多种细胞信号传导途径。本文综述了ncRNA在肿瘤中调控AS的机制，并讨论了其作为生物标志物和治疗靶点的潜在临床应用。
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.
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