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Review
. 2024 Apr 15;24(1):134.
doi: 10.1186/s12935-024-03281-w.

Micropeptides: potential treatment strategies for cancer

He Zhou  1   2 , Yan Wu  1   2 , Ji Cai  1   2 , Dan Zhang  3 , Dongfeng Lan  1   2 , Xiaofang Dai  1   2 , Songpo Liu  1   2 , Tao Song  1   2 , Xianyao Wang  1   2 , Qinghong Kong  4 , Zhixu He  5 , Jun Tan  6 , Jidong Zhang  7   8   9
Affiliations
Review

Micropeptides: potential treatment strategies for cancer

He Zhou et al. Cancer Cell Int. .

Abstract

Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although noncoding RNAs (ncRNAs) have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies have revealed that ncRNA-derived micropeptides exhibit regulatory functions in the development of many tumours. Although some of these micropeptides inhibit tumour growth, others promote it. Understanding the role of ncRNA-encoded micropeptides in cancer poses new challenges for cancer research, but also offers promising prospects for cancer therapy. In this review, we summarize the types of ncRNAs that can encode micropeptides, highlighting recent technical developments that have made it easier to research micropeptides, such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. Furthermore, based on the distribution of micropeptides in different subcellular locations, we explain the biological functions of micropeptides in different human cancers and discuss their underestimated potential as diagnostic biomarkers and anticancer therapeutic targets in clinical applications, information that may contribute to the discovery and development of new micropeptide-based tools for early diagnosis and anticancer drug development.

Keywords: Cancer; Micropeptide; Noncoding RNAs; Subcellular localization.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Several techniques for the identification of micropeptides. (A) Ribosome sequencing: identifying sORFs with coding potential. (B) Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides reliable evidence for the presence of sORF-encoded peptides (SEPs). (C) CRISPR-Cas9: Determining the function of micropeptides by knocking down the sORF of non-canonical peptides. (D) In vitro translation: assessing the encoding capacity of Sorf. (E) Bioinformatics analysis: algorithmic analysis and database search to obtain potential micropeptides. (F) Western Blot:Perform micropeptide coding and functional validation
Fig. 2
Fig. 2
Subcellular localization and mechanism of action of micropeptides in cells. Distribution of micropeptides in cell membrane(SMIM30, MIAC), cytoplasm(CIP2A-BP, YY1BM, AKT3-174AA, KRASM, NoBody, ASRPS), endoplasmic reticulum(FORCP, APPLE), and mitochondria(MP31, miPEP133)
Fig. 3
Fig. 3
Subcellular localization and mechanism of action of micropeptides in cell nucleus
Fig. 4
Fig. 4
The role of micropeptides in different types of cancer, red indicates tumor suppressor microproteins with potential pharmacological activity, while green indicates cancer-promoting peptides that can be clinically targeted.HNSCC, head and neck squamous cell carcinoma; HCC, hepatocellular carcinoma; GBM, glioblastoma; BC, breast cancer; TNBC, triple-negative breast cancer; CRC, colorectal cancer; EC, endometrial cancer
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