Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance

Abstract The human genome harbors approximately twenty thousand protein-coding genes, and a significant portion of life science research focuses on elucidating their functions and the underlying mechanisms. Recent studies have revealed that small open reading frame (sORF), originating from non-codin...

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Main Authors: Tingting Zhang, Zhang Li, Jiao Li, Yong Peng
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Molecular Cancer
Online Access:https://doi.org/10.1186/s12943-025-02278-x
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author Tingting Zhang
Zhang Li
Jiao Li
Yong Peng
author_facet Tingting Zhang
Zhang Li
Jiao Li
Yong Peng
author_sort Tingting Zhang
collection DOAJ
description Abstract The human genome harbors approximately twenty thousand protein-coding genes, and a significant portion of life science research focuses on elucidating their functions and the underlying mechanisms. Recent studies have revealed that small open reading frame (sORF), originating from non-coding RNAs or the 5’ leader sequences of messenger RNAs, can be translated into small peptides called microproteins through cap-dependent or cap-independent mechanisms. These microproteins interact with diverse molecular partners to modulate gene expression at multiple regulatory levels, thereby playing critical roles in various biological processes. Notably, sORF-encoded microproteins exhibit aberrant expression patterns in cancer and are implicated in tumor initiation and progression, expanding our understanding of cancer biology. In this review, we introduce the translational mechanisms and identification methods of microproteins, summarize their dysregulation in cancer and their biological functions in regulating gene expression, and emphasize their roles in driving hallmark events of cancer. Furthermore, we discuss their clinical significance as diagnostic and prognostic biomarkers, as well as therapeutic targets.
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spelling doaj-art-71ec83d49d0541eca87d9ac95bdfcbb82025-08-20T02:25:34ZengBMCMolecular Cancer1476-45982025-04-0124112410.1186/s12943-025-02278-xSmall open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significanceTingting Zhang0Zhang Li1Jiao Li2Yong Peng3Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityCenter for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityCenter for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityCenter for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan UniversityAbstract The human genome harbors approximately twenty thousand protein-coding genes, and a significant portion of life science research focuses on elucidating their functions and the underlying mechanisms. Recent studies have revealed that small open reading frame (sORF), originating from non-coding RNAs or the 5’ leader sequences of messenger RNAs, can be translated into small peptides called microproteins through cap-dependent or cap-independent mechanisms. These microproteins interact with diverse molecular partners to modulate gene expression at multiple regulatory levels, thereby playing critical roles in various biological processes. Notably, sORF-encoded microproteins exhibit aberrant expression patterns in cancer and are implicated in tumor initiation and progression, expanding our understanding of cancer biology. In this review, we introduce the translational mechanisms and identification methods of microproteins, summarize their dysregulation in cancer and their biological functions in regulating gene expression, and emphasize their roles in driving hallmark events of cancer. Furthermore, we discuss their clinical significance as diagnostic and prognostic biomarkers, as well as therapeutic targets.https://doi.org/10.1186/s12943-025-02278-x
spellingShingle Tingting Zhang
Zhang Li
Jiao Li
Yong Peng
Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
Molecular Cancer
title Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
title_full Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
title_fullStr Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
title_full_unstemmed Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
title_short Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance
title_sort small open reading frame encoded microproteins in cancer identification biological functions and clinical significance
url https://doi.org/10.1186/s12943-025-02278-x
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