Micropeptides Related to Tumors: Candidates for Tumor Targeted Therapies and Diagnostic Biomarkers

Volume 9, Issue 3, June 2024     |     PP. 67-78      |     PDF (284 K)    |     Pub. Date: October 30, 2024
DOI: 10.54647/biology180377    24 Downloads     1178 Views  

Author(s)

Zhang Taoyangshu, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong 637000, China
Li Dajiang, School of Pharmacy, North Sichuan Medical College, Nanchong 637000, China
Kang Aijia, School of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China
Tan Xiao, School of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China
Liu Hongmei, School of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China
Zhang Shuting, School of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, China
Yin Xinqiang, School of Pharmacy, North Sichuan Medical College, Nanchong 637000, China

Abstract
A number of RNAs, which have been annotated as non-coding RNA, encode proteins less than 100 amino acids. The ORFs less than 100 codes are called small open reading frames（sORFs）. sORFs encode proteins called micropeptides. Though many micropeptides have been identified in several species, there are gaps in mining micropeptides from thousands of ncRNAs. But developing technologies help us to find more and more sORFs and micropeptides. To date, micropeptides are found to involve in various cancers, and can be used as prognostic biomarkers and therapeutic targets. This review discusses the micropeptides which have been discovered in cancers. However, there are gaps that remain unclear. The resulting picture is micropeptides need to be deep-going. And in the future, the research of micropeptides related to cancers also will be a hot topic.

Keywords
sORFs, micropeptides, cancer, diagnostic biomarker, Targeted Therapies, ncRNAs

Cite this paper
Zhang Taoyangshu, Li Dajiang, Kang Aijia, Tan Xiao, Liu Hongmei, Zhang Shuting, Yin Xinqiang, Micropeptides Related to Tumors: Candidates for Tumor Targeted Therapies and Diagnostic Biomarkers , SCIREA Journal of Biology. Volume 9, Issue 3, June 2024 | PP. 67-78. 10.54647/biology180377

References

[ 1 ] Yin X.Q.; Jing, Y.Y.; Xu H.M. Mining for missed sORF-encoded peptides. Expert review of proteomics, 2019, 16(3): 257-266.
[ 2 ] Jing Y.Y.; Yin, X.Q. Micropeptides Identified from Human Genomes. J Proteome Res. 2022, 21(4):865- 873.
[ 3 ] Yeasmin F, Yada T, Akimitsu N. Micropeptides Encoded in Transcripts Previously Identified as Long Noncoding RNAs: A New Chapter in Transcriptomics and Proteomics. Front Genet. 2018. 9:144.
[ 4 ] Li, M.; Li, X.; Zhang, Y.; Wu, H.; Zhou, H; Ding, X.; Zhang, X.; Jin, X.; Wang, Y.; Yin, X.; Li, C.; Yang, P; Xu, H. Micropeptide MIAC Inhibits HNSCC Progression by Interacting with Aquaporin 2. J Am Chem Soc. 2020, 142(14):6708-6716.
[ 5 ] Li, M.; Liu, G.; Jin, X.; Guo, H.; Setrerrahmane, S.; Xu, X.; Li, T.; Lin, Y.; Xu, H. Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma. Mol Cancer, 2022, 21(1):181.
[ 6 ] Weintraub AS, Li CH, Zamudio AV, Sigova AA, Hannett NM, Day DS, Abraham BJ, Cohen MA, Nabet B, Buckley DL, Guo YE, Hnisz D, Jaenisch R, Bradner JE, Gray NS, Young RA. YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell. 2017, 171(7):1573-1588.e28.
[ 7 ] Wu, S.; Zhang, L.; Deng, J.; Guo, B.; Li, F.; Wang, Y.; Wu, R.; Zhang, S.; Lu, J.; Zhou, Y. A Novel Micropeptide Encoded by Y-Linked LINC00278 Links Cigarette Smoking and AR Signaling in Male Esophageal Squamous Cell Carcinoma. Cancer Res. 2020, 80(13):2790-2803. 
[ 8 ] Guo, B.; Wu, S.; Zhu, X.; Zhang, L.; Deng, J.; Li, F.; Wang, Y.; Zhang, S.; Wu, R.; Lu, J.; Zhou, Y. Micropeptide CIP2A-BP encoded by LINC00665 inhibits triple-negative breast cancer progression. EMBO Journal, 2020, 39(1): e102190.
[ 9 ] Polycarpou-Schwarz, M.; Groß, M.; Mestdagh, P.; Schott, J.; Grund, S.E.; Hildenbrand, C.; Rom, J.; Aulmann, S.; Sinn, H.P.; Vandesompele, J.; Diederichs, S. The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation. Oncogene, 2018, 37(34):4750-4768.
[ 10 ] Wu, S.; Guo, B.; Zhang, L.; Zhu, X.; Zhao, P.; Deng, J.; Zheng, J.; Li, F.; Wang, Y.; Zhang, S.; Zhang, Z.; Lu, J.; Zhou, Y. A micropeptide XBP1SBM encoded by lncRNA promotes angiogenesis and metastasis of TNBC via XBP1s pathway. Oncogene, 2022, 41(15):2163-2172. 
[ 11 ] Zhang, H.; Liao, Z.; Wang, W.; Liu, Y.; Zhu, H.; Liang, H.; Zhang, B.; Chen, X. A micropeptide JunBP regulated by TGF-β promotes hepatocellular carcinoma metastasis. Oncogene. 2023, 42(2):113-123.
[ 12 ] Zhong, C.; Xie, Z.; Shen, J.; Jia, Y.; Duan, S. LINC00665: An Emerging Biomarker for Cancer Diagnostics and Therapeutics. Cells. 2022, 11(9):1540. 
[ 13 ] Li YR, Zong RQ, Zhang HY, Meng XY, Wu FX. Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma. Front Genet. 2022. 13:861096.
[ 14 ] Xie, C.; Wang, F.Y.; Sang, Y.; Chen, B.; Huang, J.H.; He, F.J.; Li, H.; Zhu, Y.; Liu, X.; Zhuang, S.M.; Fang, J.H. Mitochondrial Micropeptide STMP1 Enhances Mitochondrial Fission to Promote Tumor Metastasis. Cancer Res. 2022, 82(13):2431-2443. 
[ 15 ] Sang, Y.; Liu, J.Y.; Wang, F.Y.; Luo, X.Y.; Chen, Z.Q.; Zhuang, S.M.; Zhu, Y. Mitochondrial micropeptide STMP1 promotes G1/S transition by enhancing mitochondrial complex IV activity. Molecular Therapy, 2022, 30(8):2844-2855.
[ 16 ] Ge, Q.; Jia, D.; Cen, D.; Qi, Y.; Shi, C.; Li, J.; Sang, L.; Yang, L.J.; He. J.; Lin, A.; Chen, S.; Wang, L. Micropeptide ASAP encoded by LINC00467 promotes colorectal cancer progression by directly modulating ATP synthase activity. J Clin Invest. 2021, 131(22): e152911.
[ 17 ] Huang, J. Z.; Chen, M.; Chen; Gao, X. C.; Zhu, S.; Huang, H.; Hu, M.; Zhu, H.; Yan, G. R. A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Molecular cell 2017,68 (1), 171-184.
[ 18 ] Liu F, Ma M, Gao A, Ma F, Ma G, Liu P, Jia C, Wang Y, Donahue K, Zhang S, Ong IM, Keles S, Li L, Xu W. PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability. EMBO J. 2021 Nov 15;40(22):e108065.
[ 19 ] Zhang Z, Deng X, Liu Y, Liu Y, Sun L, Chen F. PKM2, function and expression and regulation. Cell Biosci. 2019 Jun 26;9:52.
[ 20 ] Li, X.L.; Pongor, L.; Tang, W.; Das, S.; Muys, B.R.; Jones, M.F.; Lazar, S.B.; Dangelmaier, E.A.; Hartford, C.C.; Grammatikakis, I.; Hao, Q.; Sun, Q.; Schetter, A.; Martindale, J.L.; Tang, B.; Jenkins, L.M.; Robles, A.I.; Walker, R.L.; Ambs, S.; Chari, R.; Shabalina, S.A.; Gorospe, M.; Hussain, S.P.; Harris, C.C.; Meltzer, P.S.; Prasanth, K.V.; Aladjem, M.I.; Andresson, T.; Lal, A. A small protein encoded by a putative lncRNA regulates apoptosis and tumorigenicity in human colorectal cancer cells. Elife, 2020, 9: e53734.
[ 21 ] Li, H.; Gao, J.; Liu, L.; Zhang, S. LINC00958: A promising long non-coding RNA related to cancer. Biomed Pharmacother. 2022, 151:113087.
[ 22 ] Merino-Valverde, I.; Greco, E.; Abad, M. The microproteome of cancer: From invisibility to relevance. Exp Cell Res. 2020, 392(1):111997.
[ 23 ] Chen, B.J.; Byrne, F.L.; Takenaka, K.; Modesitt, S.C.; Olzomer, E.M.; Mills, J.D.; Farrell, R.; Hoehn, K.L.; Janitz, M. Transcriptome landscape of long intergenic non-coding RNAs in endometrial cancer. Gynecol Oncology, 2017, 147(3):654-662.
[ 24 ] Polenkowski, M.; Burbano, de Lara S.; Allister, A.B.; Nguyen, T.N.Q.; Tamura, T.; Tran, D.D.H. Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA. International Journal of Molecular Science, 2021, 23(1):58.
[ 25 ] Park, S.M.; Kang, T.I.; So, J.S. Roles of XBP1s in Transcriptional Regulation of Target Genes. Biomedicines, 2021, 9(7):791.
[ 26 ] Sun, L.; Wang, W.; Han, C.; Huang, W.; Sun, Y.; Fang, K.; Zeng, Z.; Yang, Q.; Pan, Q.; Chen, T.; Luo, X.; Chen, Y. The oncomicropeptide APPLE promotes hematopoietic malignancy by enhancing translation initiation. Mol Cell, 2021, 81(21):4493-4508.e9.
[ 27 ] Zhou, X.; Wu, X.; Lai, K.; Zhou, R.; Chen, Z.; Yang, Z.; Gao, X. Discovery of the hidden coding information in cancers: Mechanisms and biological functions. Int J Cancer. 2022, doi: 10.1002/ijc.34360. Epub ahead of print.
[ 28 ] Xiao, M.H.; Lin, Y.F.; Xie, P.P.; Chen, H.X.; Deng, J.W.; Zhang, W.; Zhao, N.; Xie, C.; Meng, Y.; Liu, X.; Zhuang, S.M.; Zhu, Y.; Fang, J.H. Downregulation of a mitochondrial micropeptide, MPM, promotes hepatoma metastasis by enhancing mitochondrial complex I activity. Mol Ther. 2022, 30(2):714-725.
[ 29 ] Ye, M.; Zhang, J.; Wei, M.; Liu, B.; Dong, K. Emerging role of long noncoding RNA-encoded micropeptides in cancer. Cancer Cell Int, 2020, 20:506.