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Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA

Identification of cancer-specific target molecules and biomarkers may be useful in the development of novel treatment and immunotherapeutic strategies. We have recently demonstrated that the expression of long noncoding (lnc) RNAs can be cancer-type specific due to abnormal chromatin remodeling and...

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Autores principales: Polenkowski, Mareike, Burbano de Lara, Sebastian, Allister, Aldrige Bernardus, Nguyen, Thi Nhu Quynh, Tamura, Teruko, Tran, Doan Duy Hai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744898/
https://www.ncbi.nlm.nih.gov/pubmed/35008483
http://dx.doi.org/10.3390/ijms23010058
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author Polenkowski, Mareike
Burbano de Lara, Sebastian
Allister, Aldrige Bernardus
Nguyen, Thi Nhu Quynh
Tamura, Teruko
Tran, Doan Duy Hai
author_facet Polenkowski, Mareike
Burbano de Lara, Sebastian
Allister, Aldrige Bernardus
Nguyen, Thi Nhu Quynh
Tamura, Teruko
Tran, Doan Duy Hai
author_sort Polenkowski, Mareike
collection PubMed
description Identification of cancer-specific target molecules and biomarkers may be useful in the development of novel treatment and immunotherapeutic strategies. We have recently demonstrated that the expression of long noncoding (lnc) RNAs can be cancer-type specific due to abnormal chromatin remodeling and alternative splicing. Furthermore, we identified and determined that the functional small protein C20orf204-189AA encoded by long intergenic noncoding RNA Linc00176 that is expressed predominantly in hepatocellular carcinoma (HCC), enhances transcription of ribosomal RNAs and supports growth of HCC. In this study we combined RNA-sequencing and polysome profiling to identify novel micropeptides that originate from HCC-specific lncRNAs. We identified nine lncRNAs that are expressed exclusively in HCC cells but not in the liver or other normal tissues. Here, DNase-sequencing data revealed that the altered chromatin structure plays a key role in the HCC-specific expression of lncRNAs. Three out of nine HCC-specific lncRNAs contain at least one open reading frame (ORF) longer than 50 amino acid (aa) and enriched in the polysome fraction, suggesting that they are translated. We generated a peptide specific antibody to characterize one candidate, NONHSAT013026.2/Linc013026. We show that Linc013026 encodes a 68 amino acid micropeptide that is mainly localized at the perinuclear region. Linc013026-68AA is expressed in a subset of HCC cells and plays a role in cell proliferation, suggesting that Linc013026-68AA may be used as a HCC-specific target molecule. Our finding also sheds light on the role of the previously ignored ’dark proteome’, that originates from noncoding regions in the maintenance of cancer.
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spelling pubmed-87448982022-01-11 Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA Polenkowski, Mareike Burbano de Lara, Sebastian Allister, Aldrige Bernardus Nguyen, Thi Nhu Quynh Tamura, Teruko Tran, Doan Duy Hai Int J Mol Sci Article Identification of cancer-specific target molecules and biomarkers may be useful in the development of novel treatment and immunotherapeutic strategies. We have recently demonstrated that the expression of long noncoding (lnc) RNAs can be cancer-type specific due to abnormal chromatin remodeling and alternative splicing. Furthermore, we identified and determined that the functional small protein C20orf204-189AA encoded by long intergenic noncoding RNA Linc00176 that is expressed predominantly in hepatocellular carcinoma (HCC), enhances transcription of ribosomal RNAs and supports growth of HCC. In this study we combined RNA-sequencing and polysome profiling to identify novel micropeptides that originate from HCC-specific lncRNAs. We identified nine lncRNAs that are expressed exclusively in HCC cells but not in the liver or other normal tissues. Here, DNase-sequencing data revealed that the altered chromatin structure plays a key role in the HCC-specific expression of lncRNAs. Three out of nine HCC-specific lncRNAs contain at least one open reading frame (ORF) longer than 50 amino acid (aa) and enriched in the polysome fraction, suggesting that they are translated. We generated a peptide specific antibody to characterize one candidate, NONHSAT013026.2/Linc013026. We show that Linc013026 encodes a 68 amino acid micropeptide that is mainly localized at the perinuclear region. Linc013026-68AA is expressed in a subset of HCC cells and plays a role in cell proliferation, suggesting that Linc013026-68AA may be used as a HCC-specific target molecule. Our finding also sheds light on the role of the previously ignored ’dark proteome’, that originates from noncoding regions in the maintenance of cancer. MDPI 2021-12-21 /pmc/articles/PMC8744898/ /pubmed/35008483 http://dx.doi.org/10.3390/ijms23010058 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Polenkowski, Mareike
Burbano de Lara, Sebastian
Allister, Aldrige Bernardus
Nguyen, Thi Nhu Quynh
Tamura, Teruko
Tran, Doan Duy Hai
Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA
title Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA
title_full Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA
title_fullStr Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA
title_full_unstemmed Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA
title_short Identification of Novel Micropeptides Derived from Hepatocellular Carcinoma-Specific Long Noncoding RNA
title_sort identification of novel micropeptides derived from hepatocellular carcinoma-specific long noncoding rna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744898/
https://www.ncbi.nlm.nih.gov/pubmed/35008483
http://dx.doi.org/10.3390/ijms23010058
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