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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8744898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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