Novel insights into noncanonical open reading frames in cancer.
Novel insights into noncanonical open reading frames in cancer.
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DOI：
10.1016/j.bbcan.2022.188755
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发表时间：
2022-06
期刊：
影响因子：
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通讯作者：
Yihan Liu;Shan Zeng;Minghua Wu
中科院分区：
文献类型：
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作者：
Yihan Liu;Shan Zeng;Minghua Wu
随着技术的进步，以前被忽视的非规范开放阅读框架（nORF）正引起越来越多的关注。然而，许多推定的nORF的翻译潜力仍然难以捉摸，和非经典肽的功能还没有系统的总结。此外，非经典肽和它们的对应蛋白质或RNA产物之间的关系仍然难以捉摸，并且尚未探索非经典肽的临床应用。在这篇综述中，我们强调了最近的技术进展，如核糖体分析，生物信息学方法和CRISPR/Cas9促进了非经典肽的研究。我们描绘了每个nORF类别的功能和nORF下的进化过程。最重要的是，我们总结了非经典肽在癌症中的多样化功能，基于它们的亚细胞位置，这反映了它们广泛参与癌细胞中的关键通路和必要的细胞活动。同时，在病理状态下，非经典肽与其相应的转录本或对应产物之间的平衡可能失调，这是它们在癌症中发挥作用所必需的。最后，我们探讨了它们在临床应用中作为诊断生物标志物和癌症治疗靶点的被低估的潜力。
With technological advances, previously neglected noncanonical open reading frames (nORFs) are drawing ever-increasing attention. However, the translation potential of numerous putative nORFs remains elusive, and the functions of noncanonical peptides have not been systemically summarized. Moreover, the relationship between noncanonical peptides and their counterpart protein or RNA products remains elusive and the clinical implementation of noncanonical peptides has not been explored. In this review, we highlight how recent technological advances such as ribosome profiling, bioinformatics approaches and CRISPR/Cas9 facilitate the research of noncanonical peptides. We delineate the features of each nORF category and the evolutionary process underneath the nORFs. Most importantly, we summarize the diversified functions of noncanonical peptides in cancer based on their subcellular location, which reflect their extensive participation in key pathways and essential cellular activities in cancer cells. Meanwhile, the equilibrium between noncanonical peptides and their corresponding transcripts or counterpart products may be dysregulated under pathological states, which is essential for their roles in cancer. Lastly, we explore their underestimated potential in clinical application as diagnostic biomarkers and treatment targets against cancer.