Abstract
The MALAT1 long noncoding RNA is strongly linked to cancer progression. Here we report a MALAT1 function in repressing the promoter of p53 (TP53) tumor suppressor gene. p21 and FAS, well-known p53 targets, were upregulated by MALAT1 knockdown in A549 human lung adenocarcinoma cells. We found that these upregulations were mediated by transcriptional activation of p53 through MALAT1 depletion. In addition, we identified a minimal MALAT1-responsive region in the P1 promoter of p53 gene. Flow cytometry analysis revealed that MALAT1-depleted cells exhibited G1 cell cycle arrest. These results suggest that MALAT1 affects the expression of p53 target genes through repressing p53 promoter activity, leading to influence the cell cycle progression.
Highlights
Recent large-scale transcriptome analyses have revealed that transcription is spread throughout the mammalian genome (>90%), including in noncoding regions
We showed that upregulation of both p21 and FAS in Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)- depleted A549 lung adenocarcinoma cells was repressed by knockdown of p53 and inhibition of p53 activity by PFT-α
We examined whether the p53 target genes were upregulated through p53 activity in MALAT1-knockdown cells
Summary
Recent large-scale transcriptome analyses have revealed that transcription is spread throughout the mammalian genome (>90%), including in noncoding regions. We showed that upregulation of both p21 and FAS in MALAT1- depleted A549 lung adenocarcinoma cells was repressed by knockdown of p53 and inhibition of p53 activity by PFT-α. This is the first report showing that MALAT1 affects expression of p53 target genes through negative regulation of specific elements in the p53 promoter. We found that upregulation of p21 and FAS in MALAT1-knockdown cells was repressed by siRNA-mediated p53 depletion (Figure 1A).
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