Kurozumi Akira, Lupold Shawn E
The James Buchanan Brady Urologic Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
The Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Asian J Urol. 2021 Oct;8(4):407-415. doi: 10.1016/j.ajur.2021.05.014. Epub 2021 Jun 6.
To review alternative polyadenylation (APA) as a mechanism of gene regulation and consider potential roles for APA in prostate cancer (PCa) biology and treatment.
An extensive review of mRNA polyadenylation, APA, and PCa literature was performed. This review article introduces APA and its association with human disease, outlines the mechanisms and components of APA, reviews APA in cancer biology, and considers whether APA may contribute to PCa progression and/or produce novel biomarkers and therapeutic targets for PCa.
Eukaryotic mRNA 3'-end cleavage and polyadenylation play a critical role in gene expression. Most human genes encode more than one polyadenylation signal, and produce more than one transcript isoform, through APA. Polyadenylation can occur throughout the gene body to generate transcripts with differing 3'-termini and coding sequence. Differences in 3'-untranslated regions length can modify post-transcriptional gene regulation by microRNAs and RNA binding proteins, and alter mRNA stability, translation efficiency, and subcellular localization. Distinctive APA patterns are associated with human diseases, tissue origins, and changes in cellular proliferation rate and differentiation state. APA events may therefore generate unique mRNA biomarkers or therapeutic targets in certain cancer types or phenotypic states.
The full extent of cancer-associated and tissue-specific APA events have yet to be defined, and the mechanisms and functional consequences of APA in cancer remain incompletely understood. There is evidence that APA is active in PCa, and that it may be an untapped resource for PCa biomarkers or therapeutic targets.
综述可变聚腺苷酸化（APA）作为一种基因调控机制，并探讨APA在前列腺癌（PCa）生物学及治疗中的潜在作用。
对mRNA聚腺苷酸化、APA及PCa相关文献进行广泛综述。本文介绍了APA及其与人类疾病的关联，概述了APA的机制和组成部分，回顾了APA在癌症生物学中的情况，并探讨了APA是否可能促进PCa进展和/或产生PCa的新型生物标志物及治疗靶点。
真核生物mRNA 3'端切割和聚腺苷酸化在基因表达中起关键作用。大多数人类基因编码多个聚腺苷酸化信号，并通过APA产生不止一种转录本异构体。聚腺苷酸化可发生在整个基因体内，以产生具有不同3'末端和编码序列的转录本。3'非翻译区长度的差异可通过微小RNA和RNA结合蛋白改变转录后基因调控，并改变mRNA稳定性、翻译效率和亚细胞定位。独特的APA模式与人类疾病、组织来源以及细胞增殖速率和分化状态的变化相关。因此，APA事件可能在某些癌症类型或表型状态中产生独特的mRNA生物标志物或治疗靶点。
与癌症相关的和组织特异性的APA事件的全貌尚未明确，且APA在癌症中的机制和功能后果仍未完全了解。有证据表明APA在PCa中具有活性，并且它可能是PCa生物标志物或治疗靶点的未开发资源。
