MicroRNA 218 acts as a tumor suppressor by targeting multiple cancer phenotype associated genes in medulloblastoma

作者: Sujatha Venkataraman , Diane K. Birks , Ilango Balakrishnan , Irina Alimova , Peter S. Harris

DOI: 10.1074/JBC.M112.396762

关键词:

摘要: Aberrant expression of microRNAs has been implicated in many cancers. We recently demonstrated differential several medulloblastoma. In this study, the regulation and function microRNA 218 (miR-218), which is significantly underexpressed medulloblastoma, was evaluated. Re-expression miR-218 resulted a significant decrease medulloblastoma cell growth, colony formation, migration, invasion, tumor sphere size. used C17.2 neural stem cells as model to show that increased results differentiation also decreased malignant transformation when transfected with oncogene REST. These suggest acts suppressor MicroRNAs by down-regulating translation target mRNAs. Targets are determined imperfect base pairing 3′-UTR mRNA. To comprehensively identify actual targets, overexpressing control were subjected high throughput sequencing RNA isolated cross-linking immunoprecipitation, technique identifies mRNAs bound RNA-induced silencing complex component protein Argonaute 2. High identified 618 genes targets included both previously validated not predicted computationally. Additional work further confirmed CDK6, RICTOR, CTSB (cathepsin B) examined functional role one these Background: differentially expressed Results: MicroRNA suppresses phenotype cells. Unbiased HITS-CLIP analysis multiple oncogenic targets. Conclusion: inhibits targeting oncogenes. Significance: miR-218-regulated pathways important pathogenesis.

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