Genomics

Dataset Information

0

MiR-204 blocks MYCN expression and is a novel a tumor suppressor in neuroblastoma tumorigenesis


ABSTRACT: Neuroblastoma is a pediatric cancer of the sympathetic nervous system. MYCN amplification is a key indicator of poor prognosis for the disease, however, mechanisms by which MYCN promotes neuroblastoma tumorigenesis are not fully understood. In this study, we analyzed global miRNA and mRNA expression profiles of tissues at different stages of tumorigenesis from TH-MYCN transgenic mice, a model of MYCN-driven neuroblastoma. Based on a Bayesian learning network model in which we compared pre-tumor ganglia from TH-MYCN+/+ mice to age-matched wild-type controls, we devised a predicted miRNA-mRNA interaction network. Among the miRNA-mRNA interactions operating during human neuroblastoma tumorigenesis, we identified that miR-204 is a tumor suppressor miRNA that inhibits a subnetwork of oncogenes strongly associated with MYCN-amplified neuroblastoma and poor patient outcome. Accordingly, we found that MYCN was bound to the miR-204 promoter and repressed miR-204 transcription, while in contrast, miR-204 directly bound MYCN mRNA and repressed MYCN expression. In support of a tumor suppressor role, miR-204 overexpression significantly inhibited neuroblastoma cell proliferation in vitro and tumorigenesis in vivo. Together these findings identify novel tumorigenic miRNA gene networks and miR-204 as a tumor suppressor that regulates MYCN expression in neuroblastoma tumorigenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100658 | GEO | 2018/06/01

REPOSITORIES: GEO

Similar Datasets

| PRJNA392443 | ENA
2017-04-01 | GSE89740 | GEO
2019-09-30 | PXD007640 | Pride
| E-GEOD-43419 | biostudies-arrayexpress
2017-09-15 | GSE72678 | GEO
| E-GEOD-55248 | biostudies-arrayexpress
2017-04-01 | GSE89739 | GEO
| E-GEOD-28401 | biostudies-arrayexpress
2016-06-01 | PXD003596 | Pride
| E-GEOD-42548 | biostudies-arrayexpress