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Daiana D. Becker-Santos



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    MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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      MA21.10 - Large-Scale Discovery of Novel Human Oncofetal Transcripts in Lung (ID 13552)

      16:20 - 16:25  |  Author(s): Daiana D. Becker-Santos

      • Abstract
      • Presentation
      • Slides

      Background

      Oncofetal genes are those expressed during both embryogenesis and tumourigenesis, but silenced in normal adult tissues. Although most described oncofetal genes have been shown to play important roles in tumour development and display potential as diagnostic and prognostic markers, this area of research remains largely unexplored. The advent of high-throughput technologies has not only allowed for large-scale discovery of biomarkers, but has also highlighted the role of non-coding RNAs from tissue development to malignant transformation. Small non-coding RNAs (sncRNAs, e.g., miRNA, snoRNA, piRNA, snRNA) are key players in gene-regulatory networks, and have shown promise as fluid-based biomarkers. In this study, we performed a comprehensive characterization of the sncRNA transcriptome of fetal, non-malignant and tumour lung tissues to identify development-associated (oncofetal) sncRNAs with roles in lung cancer, including the discovery of previously unannotated miRNAs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Here, 209 paired non-malignant/tumour lung samples from two cohorts (BCCA, n=118 and TCGA, n=91) and 25 fetal lung samples were analyzed through the platform miRMaster. This platform aligns sequence reads to the hg38 genomic build, quantifies known sncRNA species and predicts novel miRNA candidates using the mirDeep2 algorithm. The sncRNA species that had no significant alterations in expression between fetal and tumours samples, but displayed significant differential expression between fetal/non-malignant and tumour/non-malignant tissues were classified as oncofetal sncRNAs. The biological relevance of the oncofetal sncRNAs and the novel miRNA candidates was investigated by gene-target prediction and pathway enrichment analyses, using mirDIP, IID and pathDIP databases.

      4c3880bb027f159e801041b1021e88e8 Result

      Our study provides the first large-scale characterization of the lung sncRNA transcriptome in fetal, non-malignant and tumour tissues. In particular, we discovered the expression of 464 novel miRNA candidates and identified a large subset of oncofetal sncRNAs. Target prediction analysis showed that the novel miRNA candidates discovered in all lung tissues are involved in cellular processes associated with cell proliferation, migration and survival, including the Wnt, MAPK and Notch signaling pathways, which are known to be associated with the development and progression of lung cancer. Additionally, oncofetal sncRNAs were found to be associated with cell cycle control and differentiation, highlighting the functional relevance of these molecules.

      8eea62084ca7e541d918e823422bd82e Conclusion

      We have not only expanded the lung sncRNA transcriptome, but also revealed the expression of a large number of sncRNAs relevant to lung tumourigenesis that are not expressed in normal adult tissues. Our results will aid in the development of more accurate fluid-based biomarkers for the early-detection of lung cancer.

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