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| Status |
Public on Jul 09, 2019 |
| Title |
CircMYBL2 Regulates FLT3-ITD FLT3AML Translation in AML |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
CircMYBL2 is more highly expressed in AML patients with FLT3-ITD mutations than in those without the FLT3-ITD mutation. We found that circMYBL2 knockdown specifically inhibits proliferation and promotes the differentiation of FLT3-ITD AML cells in vitro and in vivo. We used the ribosome profiling and RNA-seq libraries sequenced with Illumina HiSeq 2500 to identify the mRNA that circMYBL2 targeted. Interestingly, we found that circMYBL2 significantly influences the protein level of mutant FLT3 kinase, which contributes to the activation of FLT3-ITD-dependent signaling pathways. Mechanistically, circMYBL2 enhanced the translational efficiency of FLT3 kinase by increasing the binding of PTBP1 to FLT3 mRNA. Moreover, circMYBL2 knockdown impaired the cytoactivity of inhibitor-resistant FLT3-ITD-positive cells, with a significant decrease in FLT3 kinase expression, followed by the inactivation of its downstream pathways. In summary, we are the first to reveal a circRNA that specifically influences FLT3-ITD AML and regulates FLT3 kinase levels through translational regulation, suggesting that circMYBL2 may be a potential therapeutic target for FLT3-ITD AML.
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| Overall design |
Sh-NC and sh-circMYBL2 MOLM-13 cells used
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| Contributor(s) |
Chen Y, Sun Y, Wang W |
| Citation(s) |
31387917 |
| Submission date |
Jul 08, 2019 |
| Last update date |
Jan 21, 2020 |
| Contact name |
Wen-Tao Wang |
| E-mail(s) |
wangwt8@mail.sysu.edu.cn
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| Phone |
86-20-84111736
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| Organization name |
sun yat sen university
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| Department |
School of Life Sciences
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| Lab |
Key Laboratory of Gene Engineering of the Ministry of Education
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| Street address |
No. 135, Xingang Xi Road
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510275 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA553142 |
| SRA |
SRP213599 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE133925_circshMY_ribo_rpkm_ann.txt.gz |
807.4 Kb |
(ftp)(http) |
TXT |
| GSE133925_circshMY_rna_fpkm_ann.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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