MicroRNA‐124 Negatively Regulates Nuclear Receptor Nur77

• DOI: 10.1096/fasebj.30.1_supplement.867.1
• Publication Date: 2023-11-26T16:51:37Z
• Authors: Alexa Farmer; Jordan A Beard; Apana Takwi; Yue‐ming Wang; Taosheng Chen

The nuclear receptor Nur77 is commonly upregulated in adult cancers and has oncogenic functions. an immediate‐early response gene that acts as a transcription factor to promote proliferation protect the cell from apoptosis. Conversely, can translocate mitochondria induce apoptosis upon treatment with various cytotoxic agents. Because cancer may have role progression, it of interest understand mechanism controlling its expression. MicroRNAs (miRNAs) are responsible for inhibiting translation their target genes by binding 3′UTR either degrading mRNA or preventing being translated into protein, thereby making these non‐coding endogenous RNAs vital regulators every cellular process. Several miRNAs been predicted Nur77; however, strong evidence showing regulation any miRNA lacking. In this study we used luciferase reporter assay containing screen 296 found miR‐124, most abundant brain promoting neuronal differentiation, caused greatest reduction activity. Interestingly, discovered inverse relationship Daoy medulloblastoma cells undifferentiated granule neuron precursors (GNPs) where miR‐124 downregulated. Further elevating levels exogenous expression increased viability, but knocking down via siRNA resulted opposite phenotype. Importantly, reduced expression, proliferation, tumor spheroid size 3D culture. all, be downregulated instances which upregulated, resulting proliferative state abets progression. This provides increasing potential therapy elevated Nur77. Support Funding Information work was supported American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children's Research Hospital, National Institutes Health [Grants RO1GM086415, RO1GM110034, & P30‐CA21765].