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| Status |
Public on Mar 21, 2023 |
| Title |
RNA-seq analysis of shCTR and shSF3B1 NHD13-derived HSPC (cKIT+) cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
SF3B1 is the most mutated splicing factor (SF) in myelodysplastic syndromes (MDS), clonal hematopoietic disorders with variable risk of leukemic transformation. Although the tumorigenic effects of SF3B1 mutations have been defined, the role of “non-mutated” SF3B1 in cancer remains largely unresolved. Here we identify a conserved epitranscriptomic program that steers SF3B1 translation to counteract leukemogenesis. Our analysis of human and murine pre-leukemic MDS cells reveals a remarkable SF3B1 protein increase. Selective inhibition of SF3B1 upregulation accelerates MDS-to-leukemia progression in vivo. Mechanistically, ALKBH5-driven m6A demethylation within the SF3B1 5’ UTR fine-tunes SF3B1 translation to direct splicing of central DNA repair and epigenetic regulators during transformation. Loss of 5’ UTR m6A increases SF3B1 abundance, genome stability and delays leukemia progression in vivo, supporting integrative analysis of SF3B1 molecular signatures in humans that may predict tumor mutational burden and poor prognosis. These findings highlight a post-transcriptional gene expression nexus that unveils unanticipated SF3B1-dependent cancer vulnerabilities.
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| Overall design |
2 sets of samples including shCTR and shSF3B1 were included in the study. Each sample was prepared in the biologically indpendent, matched triplicates.
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| Contributor(s) |
Ciesla M, Thi Ngoc PC, Bellodi C |
| Citation(s) |
36944332 |
| |
| Submission date |
Mar 11, 2022 |
| Last update date |
Jun 24, 2023 |
| Contact name |
Phuong Cao Thi Ngoc |
| Organization name |
Lund University
|
| Street address |
BMC, B1222b, Klinikgatan 26
|
| City |
Lund |
| ZIP/Postal code |
SE-221 84 |
| Country |
Sweden |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE189586 |
m6A-driven translation control of SF3B1 steers splicing to direct genome integrity and leukemogenesis |
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| Relations |
| BioProject |
PRJNA815341 |
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