Tano Keiko, Onoguchi-Mizutani Rena, Yeasmin Fouzia, Uchiumi Fumiaki, Suzuki Yutaka, Yada Tetsushi, Akimitsu Nobuyoshi
Isotope Science Center, The University of Tokyo, Tokyo, Japan.
Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken, Japan.
Front Genet. 2018 Mar 26;8:208. doi: 10.3389/fgene.2017.00208. eCollection 2017.
The MALAT1 long noncoding RNA is strongly linked to cancer progression. Here we report a MALAT1 function in repressing the promoter of tumor suppressor gene. and , 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 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 promoter activity, leading to influence the cell cycle progression.
MALAT1长链非编码RNA与癌症进展密切相关。在此我们报告MALAT1在抑制肿瘤抑制基因启动子方面的功能。在A549人肺腺癌细胞中，通过敲低MALAT1， 和 （著名的p53靶基因）的表达上调。我们发现这些上调是通过MALAT1缺失介导的p53转录激活实现的。此外，我们在 基因的P1启动子中鉴定出一个最小的MALAT1反应区域。流式细胞术分析显示，缺失MALAT1的细胞表现出G1期细胞周期阻滞。这些结果表明，MALAT1通过抑制 启动子活性影响p53靶基因的表达，进而影响细胞周期进程。
