Unknown,Transcriptomics,Genomics,Proteomics

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Long Noncoding RNA MALAT1 Controls Cell Cycle Progression by Regulating the Expression of Oncogenic Transcription Factor B-MYB

ABSTRACT: 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 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).

ORGANISM(S): Homo sapiens

SUBMITTER: Kevin Becker

PROVIDER: E-GEOD-44240 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB.

Tripathi Vidisha V Shen Zhen Z Chakraborty Arindam A Giri Sumanprava S Freier Susan M SM Wu Xiaolin X Zhang Yongqing Y Gorospe Myriam M Prasanth Supriya G SG Lal Ashish A Prasanth Kannanganattu V KV

PLoS genetics 20130321 3

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 ...[more]

PMID: 23555285

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