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| Status |
Public on Oct 03, 2024 |
| Title |
Drosha loss drives pineoblastoma by upregulating Ccnd2 [miR-eCLIP] |
| Organism |
Mus musculus |
| Experiment type |
Other
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| 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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| Overall design |
We used miR-eCLIP to identify transcripts targeted by microRNAs in pineal tumor cells (IPRb1).
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| Contributor(s) |
Fraire CR, Desai K, Mendyka L, Obalaparum U, Sebastian T, Rajaram V, Chen KS |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Feb 15, 2024 |
| Last update date |
Oct 03, 2024 |
| Contact name |
Kenneth S Chen |
| E-mail(s) |
kenneth.chen@utsouthwestern.edu
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| Organization name |
UT Southwestern
|
| Department |
Pediatrics
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| Street address |
5323 Harry Hines Blvd
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| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE255914 |
Drosha loss drives pineoblastoma by upregulating Ccnd2 |
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| Relations |
| BioProject |
PRJNA1077084 |
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