Cao Yu, Lin Minglin, Bu Yiwen, Ling Hongyan, He Yingchun, Huang Chenfei, Shen Yi, Song Bob, Cao Deliang
Department of Medical Microbiology, Immunology and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
University of Missouri-Kansas City, Kansas City, MO 64108, USA.
Int J Oncol. 2017 May;50(5):1671-1682. doi: 10.3892/ijo.2017.3918. Epub 2017 Mar 20.
Long non-coding RNAs (lncRNAs) function in the development and progression of cancer, but only a small portion of lncRNAs have been characterized to date. A novel lncRNA transcript, 2.53 kb in length, was identified by transcriptome sequencing analysis, and was named p53-inducible cancer-associated RNA transcript 1 (PICART1). PICART1 was found to be upregulated by p53 through a p53-binding site at -1808 to -1783 bp. In breast and colorectal cancer cells and tissues, PICART1 expression was found to be decreased. Ectopic expression of PICART1 suppressed the growth, proliferation, migration, and invasion of MCF7, MDA-MB-231 and HCT116 cells whereas silencing of PICART1 stimulated cell growth and migration. In these cells, the expression of PICART1 suppressed levels of p-AKT (Thr308 and Ser473) and p-GSK3β (Ser9), and accordingly, β-catenin, cyclin D1 and c-Myc expression were decreased, while p21Waf/cip1 expression was increased. Together these data suggest that PICART1 is a novel p53-inducible tumor-suppressor lncRNA, functioning through the AKT/GSK3β/β-catenin signaling cascade.
长链非编码RNA（lncRNAs）在癌症的发生发展过程中发挥作用，但迄今为止只有一小部分lncRNAs得到了表征。通过转录组测序分析鉴定出一种长度为2.53 kb的新型lncRNA转录本，并将其命名为p53诱导的癌症相关RNA转录本1（PICART1）。发现PICART1通过位于-1808至-1783 bp处的p53结合位点被p53上调。在乳腺癌和结肠癌细胞及组织中，发现PICART1表达降低。PICART1的异位表达抑制了MCF7、MDA-MB-231和HCT116细胞的生长、增殖、迁移和侵袭，而PICART1的沉默则刺激了细胞生长和迁移。在这些细胞中，PICART1的表达抑制了p-AKT（Thr308和Ser473）和p-GSK3β（Ser9）的水平，相应地，β-连环蛋白、细胞周期蛋白D1和c-Myc的表达降低，而p21Waf/cip1的表达增加。这些数据共同表明，PICART1是一种新型的p53诱导的肿瘤抑制lncRNA，通过AKT/GSK3β/β-连环蛋白信号级联发挥作用。
