Zhu Liangjun, Zhang Chongguo, Xue Jiao, He Xuezhi, Yin Dandan, Zhu Qingqing, Shu Yongqian, De Wei
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, PR China.
Department of Radiation Oncology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, PR China.
J Cancer. 2021 Oct 17;12(23):7069-7078. doi: 10.7150/jca.63415. eCollection 2021.
It was recently demonstrated that long noncoding RNAs (lncRNAs) have key regulation functions in the biology of human cancer. The current study aimed to determine the expression, clinicopathological characteristics and functional roles of lncRNA PCAT18 in gastric cancer (GC). By analysis of (Gene Expression Omnibus) GEO and TCGA data, following experimental verification, we identified the function role and molecular mechanism of PCAT18 in tumorigenesis of GC. We discovered that PCAT18 is significantly decreased in paired GC tissues and correlates with a poor outcome. Mechanistic studies found that suppression of the expression of EZH2 could prevent its binding to the PCAT18's promoter region and decrease H3K27's trimethylation modification. In addition, PCAT18 could adjust cell proliferation of GC as well as . Further mechanism research revealed that PCAT18 could regulate the expression of p16 by interacting with miR-570a-3p, thus inhibiting cell proliferation of GC. Our results have shown that the histone modification-mediated epigenetic suppression of PCAT18 and its essential role of PCAT18 in GC oncogenesis, which could provide a theoretical basis for GC therapy.
最近有研究表明，长链非编码RNA（lncRNAs）在人类癌症生物学中具有关键调控功能。本研究旨在确定lncRNA PCAT18在胃癌（GC）中的表达、临床病理特征及功能作用。通过对基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据进行分析，并经实验验证，我们确定了PCAT18在GC肿瘤发生中的功能作用及分子机制。我们发现，在配对的GC组织中PCAT18显著降低，且与不良预后相关。机制研究发现，抑制EZH2的表达可阻止其与PCAT18启动子区域结合，并降低H3K27的三甲基化修饰。此外，PCAT18还可调节GC的细胞增殖。进一步的机制研究表明，PCAT18可通过与miR-570a-3p相互作用来调节p16的表达，从而抑制GC的细胞增殖。我们的研究结果表明，组蛋白修饰介导的PCAT18表观遗传抑制及其在GC肿瘤发生中的重要作用，可为GC治疗提供理论依据。
