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| Status |
Public on May 16, 2014 |
| Title |
Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The long noncoding MALAT1 RNA is upregulated in cancer tissues and its elevated expression is associated with hyper-proliferation, but the underlying mechanism is poorly understood. We demonstrate that MALAT1 levels are regulated during normal cell cycle progression. Genome-wide transcriptome analyses in normal human diploid fibroblasts reveal that MALAT1 modulates the expression of cell cycle genes, and is required for G1/S and mitotic progression. Depletion of MALAT1 leads to activation of p53 and its target genes. The cell cycle defects observed in MALAT1-depleted cells are sensitive to p53 levels, indicating that p53 is a major downstream mediator of MALAT1 activity. Furthermore, MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing. In human cells, MALAT1 promotes cellular proliferation by modulating the expression and/or premRNA processing of cell cycle-regulated transcription factors. These findings provide mechanistic insights on the role of MALAT1 in regulating cellular proliferation.
Keywords: MALAT1; MALAT-1, NEAT2, ncRNA; E2F, alternative splicing; pre-mRNA splicing factors
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| Overall design |
WI38 cells (normal human diploid fibroblasts) were transfected with a control oligo (CTR) or antisense oligos to MALAT1 and RNA was isolated after 48 hr. Two antisense oligos were use for MALAT1 (AS-1 and AS-2). Arrays were done for 3 sets of samples in triplicate (control, AS-1 and AS-2).
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| Contributor(s) |
Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, Zhang Y, Gorospe M, Prasanth SG, Lal A, Prasanth KV |
| Citation(s) |
23555285 |
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| Submission date |
Feb 11, 2013 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA189230 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE44240_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| GSE44240_non-normalized.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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