Oncogenic MicroRNA-20a is downregulated by the HIF-1α/c-MYC pathway in IDH1 R132H-mutant glioma

Highlights: • MiR-20a is down-regulated in IDH1 R132H mutant-glioma. • IDH1 R132H mutation attenuates miR-20a expression via HIF-1α/c-MYC pathway. • The downregulated miR-20a contributes to the therapeutic sensitivity of IDH1 mutant gliomas. Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified as one of the earliest events in gliomagenesis, occurring in over 70% of low grade gliomas and are present in the vast majority of secondary glioblastoma (GBM) that develop from these low-grade lesions. The aim of this study was to investigate whether the IDH1 R132H mutation influences the expression of oncogenic miR-20a and shed light on the underlying molecular mechanisms. The findings of the current study demonstrate presence of the IDH1 R132H mutation in primary human glioblastoma cell lines with upregulated HIF-1α expression, downregulating c-MYC activity and resulting in a consequential decrease in miR-20a, which is responsible for cell proliferation and resistance to standard temozolomide treatment. Elucidating the mechanism of oncogenic miR-20a activity introduces its role among well-established signaling pathways (i.e. HIF/c-MYC) and may be a meaningful prognostic biomarker or target for novel therapies among patients with IDH1-mutant glioma.