Role of microRNAs Located on Chromosome Arm 10q in Malignant Gliomas.

摘要: Deletions of chromosome arm 10q are found in most glioblastomas and subsets lower grade gliomas. Mutations the PTEN gene at 10q23.3 restricted to less than half 10q-deleted gliomas, suggesting additional glioma-associated tumor suppressors on 10q. We investigated 64 astrocytic gliomas different malignancy grades for aberrant expression 16 microRNAs (miRNAs) Thereby, we identified four miRNAs (miR-107, miR-146b-5p, miR-346, miR-1287-5p) whose was frequently down-regulated anaplastic astrocytomas and/or glioblastomas. DNA methylation analyses revealed 5'-CpG site hypermethylation miR-346 more two-thirds primary glioblastomas, while miR-146b-5p frequent IDH1-mutant secondary Overexpression either glioma cell lines reduced proliferation increased caspase-3/7 activity. Expression miRNA overexpressing cells 3'-untranslated region luciferase reporter assays evidence that these post-transcriptionally regulate glioma-relevant genes, including CDK6 (miR-107), EGFR (miR-146b-5p, miR-1287-5p), TERT SEMA6A (miR-346), all which overexpressed malignant situ. In summary, show 10q-located miR-107, miR-1287-5p thereby may support overexpression important growth-promoting genes.