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Drosha loss drives pineoblastoma by upregulating Ccnd2 [RNAseq of ceritinib treatment]

GSE255910 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/10/03 Platform GPL30172
Summary
Mutations in the microRNA processing genes DICER1 and DROSHA drive childhood cancers such as pineoblastoma, a brain tumor that resembles undifferentiated precursors of the pineal gland. To understand how microRNAs regulate proliferation of these progenitors, we developed a mouse model of pineoblastoma by ablating Drosha or Dicer1 in the developing pineal gland. The tumors that arise in these models resemble proliferative, undifferentiated embryonic progenitors. They are marked by loss of microRNAs, including the let-7 family, and de-repression of let-7 target genes. One upregulated let-7 target gene is the oncofetal transcription factor Plagl2, which activates expression of key pro-growth genes Igf2 and Ccnd2, and we show that small molecules targeting these two drivers block tumor growth. Thus, our results demonstrate that tumors driven by loss of microRNA processing may be therapeutically targeted by inhibiting downstream drivers of proliferation.
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Also filed as BioProject PRJNA1077083 and SRA study SRP490108. Searching any of these in the dataset finder brings you back here.

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