Novel insights into noncanonical open reading frames in cancer

Yihan Liu; Shan Zeng; Minghua Wu

doi:10.1016/j.bbcan.2022.188755

Novel insights into noncanonical open reading frames in cancer

Biochim Biophys Acta Rev Cancer. 2022 Jul;1877(4):188755. doi: 10.1016/j.bbcan.2022.188755. Epub 2022 Jun 28.

Authors

Yihan Liu¹, Shan Zeng², Minghua Wu³

Affiliations

¹ 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.
² 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. Electronic address: zengshan2000@csu.edu.cn.
³ 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. Electronic address: wuminghua554@aliyun.com.

PMID: 35777601
DOI: 10.1016/j.bbcan.2022.188755

Abstract

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.

Keywords: Cancer; Micropeptide; Noncanonical open reading frame; Noncanonical peptide; circRNA.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Humans
Neoplasms* / genetics
Neoplasms* / metabolism
Open Reading Frames / genetics
Peptides / genetics
RNA
Ribosomes* / genetics

Substances

Peptides
RNA