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Series GSE133925 Query DataSets for GSE133925
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
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.
Overall design Sh-NC and sh-circMYBL2 MOLM-13 cells used
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
Phone 86-20-84111736
Organization name sun yat sen university
Department School of Life Sciences
Lab Key Laboratory of Gene Engineering of the Ministry of Education
Street address No. 135, Xingang Xi Road
City Guangzhou
State/province Guangdong
ZIP/Postal code 510275
Country China
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM3930171 Sh-NC rep1 (ribo)
GSM3930172 Sh-NC rep2 (ribo)
GSM3930173 Sh-cricMY1 rep1 (ribo)
BioProject PRJNA553142
SRA SRP213599

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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
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Raw data are available in SRA
Processed data are available on Series record

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