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| Status |
Public on Mar 01, 2015 |
| Title |
Gene expression profiling of human neuroblastoma BE(2)-C cells with MEIS2 depletion |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis.
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| Overall design |
Affymetrix microarray assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of BE(2)-C cells infected with lentiviruses expressing either shGFP or shMEIS2-43 for 48 hours.
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| Contributor(s) |
Ding H, Zha Y |
| Citation(s) |
25210800 |
| |
| Submission date |
Mar 18, 2014 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Justin Choi |
| E-mail(s) |
jeochoi@gmail.com
|
| Phone |
1-706-721-6757
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| Organization name |
Georgia Regents University
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| Department |
Cancer Center
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| Street address |
1410 Laney Walker Blvd.
|
| City |
Augusta |
| State/province |
GA |
| ZIP/Postal code |
30912 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA242141 |
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