bims-micpro Biomed News
on Discovery and characterization of microproteins
Issue of 2024–08–11
two papers selected by
Thomas Farid Martínez, University of California, Irvine
  1. Discovery of high-expressing lncRNA-derived sORFs as potential tumor-associated antigens in hepatocellular carcinoma.
  2. The role of polypeptides encoded by ncRNAs in cancer.
  1. Genes Genomics. 2024 Aug 08.
    Discovery of high-expressing lncRNA-derived sORFs as potential tumor-associated antigens in hepatocellular carcinoma.
    Yooeun Kim, Hongseok Ha, Kwangsoo Kim.
       BACKGROUND: This study is based on deep mining of Ribo-seq data for the identification of lncRNAs that have highly expressed sORFs in HCC. In this paper, dynamic prospects associated with sORFs acting as newly defined tumor-specific epitopes are discussed with possible improvement in strategies for tumor immunotherapy.
    OBJECTIVE: Using ribosome profiling to identify and characterize sORFs within lncRNAs in HCC, identify potential therapeutic targets and tumor-specific epitopes applicable for immunotherapy.
    METHODS: MetamORF performed the identification of sORFs with deep analysis of the data of ribosome profiling in lncRNAs associated with HCC. The translation efficiency in these molecules was estimated, and epitope prediction was done by pVACbind. Peptide search was done to check the presence of micropeptides translated from these identified sORFs. validated translational activity and identified potential epitopes.
    RESULTS: Higher translation efficiency was noted in the case of lncRNAs associated with HCC compared to normal tissues. Of particular note is ORF3418981, which results in the highest expression and has supporting experimental evidence at the protein level. Epitope prediction identified a putative epitope at the C-terminus of ORF3418981.
    CONCLUSIONS: This study uncovers the as-yet-unknown potential of lncRNA-derived sORFs as sources of tumor antigens, shifting the research focus from protein-coding genes to non-coding RNAs also in the HCC context. Moreover, this study highlights the contribution of a subset of lncRNAs, especially LINC00152, to the development of tumors and modulation of the immune response by its sORFs.
    Keywords:  Hepatocellular carcinoma; Long non-coding RNAs; Ribo-seq; Small open reading frames; Translation efficiency; Tumor-specific antigens
    DOI:  https://doi.org/10.1007/s13258-024-01549-z
  2. Gene. 2024 Aug 03. pii: S0378-1119(24)00698-X. [Epub ahead of print]928 148817
    The role of polypeptides encoded by ncRNAs in cancer.
    Jiayuan Huang, Ping Yang, Wei Pan, Fan Wu, Jianhua Qiu, Zhongliang Ma.
      It was previously thought that ncRNA could not encode polypeptides, but recent reports have challenged this notion. As research into ncRNA progresses, it is increasingly clear that it serves roles beyond traditional mechanisms, playing significant regulatory roles in various diseases, notably cancer, which is responsible for 70% of human deaths. Numerous studies have highlighted the diverse regulatory mechanisms of ncRNA that are pivotal in cancer initiation and progression. The role of ncRNA-encoded polypeptides in cancer regulation has gained prominence. This article explores the newly identified regulatory functions of these polypeptides in three types of ncRNA-lncRNA, pri-miRNA, and circRNA. These polypeptides can interact with proteins, influence signaling pathways, enhance miRNA stability, and regulate cancer progression, malignancy, resistance, and other clinical challenges. Furthermore, we discuss the evolutionary significance of these polypeptides in the transition from RNA to protein, examining their emergence and conservation throughout evolution.
    Keywords:  cancer; circRNA; lncRNA; ncRNA; pri-miRNA; short peptides
    DOI:  https://doi.org/10.1016/j.gene.2024.148817
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