Integrated Dissection of lncRNA-Perturbated Triplets Reveals Novel Prognostic Signatures Across Cancer Types
Autor: | Dianjing Guo, Yunzhen Wei, Yingzhang Huang, Limeng Zhou |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
congenital
hereditary and neonatal diseases and abnormalities pan-cancer analysis Lung Neoplasms Datasets as Topic macromolecular substances Computational biology Adenocarcinoma Biology Article Catalysis Conserved sequence Inorganic Chemistry lcsh:Chemistry lncRNA Trinucleotide Repeats lncRNA-perturbated triplets Neoplasms Cancer genome microRNA Biomarkers Tumor medicine Humans Gene Regulatory Networks RNA Messenger Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Messenger RNA prognostic signatures Gene Expression Profiling Organic Chemistry Cancer Genomics General Medicine Prognosis medicine.disease Long non-coding RNA Computer Science Applications Gene Expression Regulation Neoplastic MicroRNAs lcsh:Biology (General) lcsh:QD1-999 A549 Cells Potential biomarkers RNA Long Noncoding Transcriptome |
Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6087, p 6087 (2020) International Journal of Molecular Sciences Volume 21 Issue 17 |
ISSN: | 1661-6596 1422-0067 |
Popis: | Long noncoding RNA (lncRNA)/microRNA(miRNA)/mRNA triplets contribute to cancer biology. However, identifying significative triplets remains a major challenge for cancer research. The dynamic changes among factors of the triplets have been less understood. Here, by integrating target information and expression datasets, we proposed a novel computational framework to identify the triplets termed as &ldquo lncRNA-perturbated triplets&rdquo We applied the framework to five cancer datasets in The Cancer Genome Atlas (TCGA) project and identified 109 triplets. We showed that the paired miRNAs and mRNAs were widely perturbated by lncRNAs in different cancer types. LncRNA perturbators and lncRNA-perturbated mRNAs showed significantly higher evolutionary conservation than other lncRNAs and mRNAs. Importantly, the lncRNA-perturbated triplets exhibited high cancer specificity. The pan-cancer perturbator OIP5-AS1 had higher expression level than that of the cancer-specific perturbators. These lncRNA perturbators were significantly enriched in known cancer-related pathways. Furthermore, among the 25 lncRNA in the 109 triplets, lncRNA SNHG7 was identified as a stable potential biomarker in lung adenocarcinoma (LUAD) by combining the TCGA dataset and two independent GEO datasets. Results from cell transfection also indicated that overexpression of lncRNA SNHG7 and TUG1 enhanced the expression of the corresponding mRNA PNMA2 and CDC7 in LUAD. Our study provides a systematic dissection of lncRNA-perturbated triplets and facilitates our understanding of the molecular roles of lncRNAs in cancers. |
Databáze: | OpenAIRE |
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