MYC and MYCN positively regulate expression of miR-9 (Ma et ...

created [InstanceEdit:9816162] Orlic-Milacic, Marija, 2022-09-01
dbId 9816163
displayName MYC and MYCN positively regulate expression of miR-9 (Ma et ...
literatureReference
modified [InstanceEdit:9932147] Orlic-Milacic, Marija, 2024-12-17
schemaClass Summation
text MYC and MYCN positively regulate expression of miR-9 (Ma et al. 2010; Liu et al. 2013; DA Silva Oliveira et al. 2017). When MYC is ectopically expressed in human mammary epithelial cell line HMLE, increase in MYC expression level correlates with an increase in the level of mature miR-9. miR-9 can be generated by the processing of any of three primary transcripts encoded by three distinct genes, MIR9-1, MIR9-2, and MIR9-3. Among the three encoding genes, the transcription of miR-9-3 is upregulated most strongly by the MYC transcription factor. When an inducible MYCN-ER fusion protein is expressed in human neuroblastoma cell line SHEP, miR-9 expression level increases comparable to the increase in the expression of the miR-17-92 positive control, whose expression is known to be activated by MYCN through direct promoter binding. MYC binding at the MIR9-3 locus is associated with elevated H3K4me3 at the MIR9-3 locus, a marker of transcriptionally active chromatin binding. While a peak for MYC binding was also observed at MIR9-1 and MIR9-2 loci, these two regions exhibited low occupancy by H3K4me3 (a mark of activated chromatin) and relatively high occupancy by H3K27me3 (a mark of repressed chromatin). Hence, among the three miR-9-encoding genes, the transcription of mir-9-3 is the most responsive to transcriptional activation by MYC/MYCN. In a group of over twenty stage 4 neuroblastoma tumors, tumors with MYCN gene amplification showed more than twofold upregulation of miR-9 expression relative to tumors with no MYCN gene amplification (Ma et al. 2010). Induced overexpression of MYC in human embryonic kidney cell line HEK293 leads to upregulation of miR-9 (Liu et al. 2013). In gastric cancer, MYC amplification correlates with overexpression of miR-9 (DA Silva Oliveira et al. 2017). MYC was also shown to be enriched on the promoter of the MIR9-1 gene by ChIP in human fibroblast cell lines HFL-1 and MRC-5 and to stimulate miR-9-1 expression in both mouse and human (Qin et al. 2022).
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