Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China; Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Biochim Biophys Acta Rev Cancer. 2022 Jul;1877(4):188755. doi: 10.1016/j.bbcan.2022.188755. Epub 2022 Jun 28.
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.
随着技术的进步，以前被忽视的非规范开放阅读框（nORF）正受到越来越多的关注。然而，大量假定的 nORF 的翻译潜力仍然难以捉摸，非规范肽的功能也没有得到系统的总结。此外，非规范肽与其对应蛋白或 RNA 产物之间的关系仍然难以捉摸，非规范肽的临床应用也尚未得到探索。在这篇综述中，我们强调了核糖体分析、生物信息学方法和 CRISPR/Cas9 等最近的技术进步如何促进非规范肽的研究。我们描述了每个 nORF 类别的特征和 nORFs 背后的进化过程。最重要的是，我们根据非规范肽在癌症中的亚细胞定位总结了它们在癌症中的多样化功能，这反映了它们在癌细胞中关键途径和基本细胞活动中的广泛参与。同时，在病理状态下，非规范肽与其相应的转录本或对应产物之间的平衡可能会失调，这对它们在癌症中的作用至关重要。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治疗癌症靶点的被低估的潜力。
