Unveiling a Ghost Proteome in the Glioblastoma Non-Coding RNAs

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Jan 10

PMID 35004666

Authors

Tristan Cardon

Isabelle Fournier

Michel Salzet

Affiliations

Soon will be listed here.

Abstract

Glioblastoma is the most common brain cancer in adults. Nevertheless, the median survival time is 15 months, if treated with at least a near total resection and followed by radiotherapy in association with temozolomide. In glioblastoma (GBM), variations of non-coding ribonucleic acid (ncRNA) expression have been demonstrated in tumor processes, especially in the regulation of major signaling pathways. Moreover, many ncRNAs present in their sequences an Open Reading Frame (ORF) allowing their translations into proteins, so-called alternative proteins (AltProt) and constituting the "ghost proteome." This neglected world in GBM has been shown to be implicated in protein-protein interaction (PPI) with reference proteins (RefProt) reflecting involvement in signaling pathways linked to cellular mobility and transfer RNA regulation. More recently, clinical studies have revealed that AltProt is also involved in the patient's survival and bad prognosis. We thus propose to review the ncRNAs involved in GBM and highlight their function in the disease.

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References

Huang J, Chen M, Chen D, Gao X, Zhu S, Huang H . A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Mol Cell. 2017; 68(1):171-184.e6. DOI: 10.1016/j.molcel.2017.09.015. View

Wen H, Li Z, Song S, Xu L, Tong X, Yan H . Silencing of lncRNA LBX2-AS1 suppresses glioma cell proliferation and metastasis through the Akt/GSK3β pathway in vitro. Acta Biochim Biophys Sin (Shanghai). 2021; 53(4):446-453. DOI: 10.1093/abbs/gmab011. View

Fouillot N, Tlouzeau S, Rossignol J . Translation of the hepatitis B virus P gene by ribosomal scanning as an alternative to internal initiation. J Virol. 1993; 67(8):4886-95. PMC: 237876. DOI: 10.1128/JVI.67.8.4886-4895.1993. View

Meng N, Chen M, Chen D, Chen X, Wang J, Zhu S . Small Protein Hidden in lncRNA Promotes "Cancerous" RNA Splicing and Tumorigenesis. Adv Sci (Weinh). 2020; 7(10):1903233. PMC: 7237858. DOI: 10.1002/advs.201903233. View

Li S . Regulation of Ribosomal Proteins on Viral Infection. Cells. 2019; 8(5). PMC: 6562653. DOI: 10.3390/cells8050508. View

Fang Y, Fullwood M . Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genomics Proteomics Bioinformatics. 2016; 14(1):42-54. PMC: 4792843. DOI: 10.1016/j.gpb.2015.09.006. View

Greene J, Baird A, Brady L, Lim M, Gray S, McDermott R . Circular RNAs: Biogenesis, Function and Role in Human Diseases. Front Mol Biosci. 2017; 4:38. PMC: 5459888. DOI: 10.3389/fmolb.2017.00038. View

Bazzini A, Johnstone T, Christiano R, Mackowiak S, Obermayer B, Fleming E . Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J. 2014; 33(9):981-93. PMC: 4193932. DOI: 10.1002/embj.201488411. View

DLima N, Ma J, Winkler L, Chu Q, Loh K, Corpuz E . A human microprotein that interacts with the mRNA decapping complex. Nat Chem Biol. 2016; 13(2):174-180. PMC: 5247292. DOI: 10.1038/nchembio.2249. View

10.

Shi M, Zhang X, Yu H, Xiang S, Xu L, Wei J . DDX11-AS1 as potential therapy targets for human hepatocellular carcinoma. Oncotarget. 2017; 8(27):44195-44202. PMC: 5546473. DOI: 10.18632/oncotarget.17409. View

11.

Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M . Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010; 17(1):98-110. PMC: 2818769. DOI: 10.1016/j.ccr.2009.12.020. View

12.

Ingolia N . Ribosome profiling: new views of translation, from single codons to genome scale. Nat Rev Genet. 2014; 15(3):205-13. DOI: 10.1038/nrg3645. View

13.

Murgoci A, Cardon T, Aboulouard S, Duhamel M, Fournier I, Cizkova D . Reference and Ghost Proteins Identification in Rat C6 Glioma Extracellular Vesicles. iScience. 2020; 23(5):101045. PMC: 7182720. DOI: 10.1016/j.isci.2020.101045. View

14.

Cardon T, Franck J, Coyaud E, Laurent E, DAmato M, Maffia M . Alternative proteins are functional regulators in cell reprogramming by PKA activation. Nucleic Acids Res. 2020; 48(14):7864-7882. PMC: 7641301. DOI: 10.1093/nar/gkaa277. View

15.

Cardon T, Herve F, Delcourt V, Roucou X, Salzet M, Franck J . Optimized Sample Preparation Workflow for Improved Identification of Ghost Proteins. Anal Chem. 2019; 92(1):1122-1129. DOI: 10.1021/acs.analchem.9b04188. View

16.

Liu W, Ma J, Cheng Y, Zhang H, Luo W, Zhang H . HMMR antisense RNA 1, a novel long noncoding RNA, regulates the progression of basal-like breast cancer cells. Breast Cancer (Dove Med Press). 2016; 8:223-229. PMC: 5125767. DOI: 10.2147/BCTT.S119997. View

17.

Chen M, Medarova Z, Moore A . Role of microRNAs in glioblastoma. Oncotarget. 2021; 12(17):1707-1723. PMC: 8378762. DOI: 10.18632/oncotarget.28039. View

18.

Minati L, Firrito C, Del Piano A, Peretti A, Sidoli S, Peroni D . One-shot analysis of translated mammalian lncRNAs with AHARIBO. Elife. 2021; 10. PMC: 7932693. DOI: 10.7554/eLife.59303. View

19.

Yanovich-Arad G, Ofek P, Yeini E, Mardamshina M, Danilevsky A, Shomron N . Proteogenomics of glioblastoma associates molecular patterns with survival. Cell Rep. 2021; 34(9):108787. DOI: 10.1016/j.celrep.2021.108787. View

20.

DeOcesano-Pereira C, Machado R, Chudzinski-Tavassi A, Sogayar M . Emerging Roles and Potential Applications of Non-Coding RNAs in Glioblastoma. Int J Mol Sci. 2020; 21(7). PMC: 7178171. DOI: 10.3390/ijms21072611. View