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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [mRNA]

ABSTRACT: Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [mRNA]

PROVIDER: PRJNA870488 | ENA |

REPOSITORIES: ENA

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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias

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Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [mRNA]

Project description:Background: Neuroendocrine neoplasms (NENs) are mutationally quiet, and epigenetic mechanisms drive their development and progression. We aim to comprehensively characterize the microRNA (miRNA) profile of NENs, and explore downstream targets and their epigenetic modulation. Material and Methods: In total, 84 cancer-related miRNAs were analyzed in 84 NEN samples from lung and gastroenteropancreatic GEP origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N=63) and methylomics (N=30) were performed to predict miRNA target genes, signaling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas (TCGA) cohorts and in NEN cell lines. Results: We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signaling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. Conclusion: In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patient.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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microRNA profiling in different grading of gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

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