He Xuezhi, Wang Jing, Chen Jin, Han Liang, Lu Xiyi, Miao Dengshun, Yin Dandan, Geng Qinghe, Zhang Erbao
Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Mol Ther Nucleic Acids. 2019 Dec 6;18:605-616. doi: 10.1016/j.omtn.2019.09.024. Epub 2019 Oct 1.
Dysregulated expression of long non-coding RNAs (lncRNAs) has been reported in many types of cancers, indicating that it has important regulatory roles in human cancer biology. Recently, lncRNA urothelial cancer-associated 1 (UCA1) was shown to be dysregulated in many cancer types, but the detailed mechanisms remain largely unknown. In our study, we found that upregulated UCA1 is associated with poor prognosis in gastric cancer patients. Further experiments revealed that UCA1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. Moreover, RNA sequencing (RNA-seq) analysis revealed that UCA1 knockdown preferentially affected genes that are linked to cell proliferation, cell cycle, and cell migration. Mechanistically, UCA1 promotes cell proliferation progression through repressing p21 and Sprouty RTK signaling antagonist 1 (SPRY1) expression by binding to EZH2. We found that UCA1 could mediate the trimethylation of H3K27 in promoters of p21 and SPRY1. To our knowledge, this is the first report showing the global gene profile of downstream targets of UCA1 in the progression of gastric cancer. Collectively, our data reveal the important roles of UCA1 in gastric cancer (GC) oncogenesis.
已有报道称，多种类型的癌症中均存在长链非编码RNA（lncRNA）表达失调的情况，这表明其在人类癌症生物学中具有重要的调控作用。最近，有研究表明，lncRNA尿路上皮癌相关1（UCA1）在多种癌症类型中表达失调，但其详细机制仍不清楚。在我们的研究中，我们发现UCA1表达上调与胃癌患者的不良预后相关。进一步的实验表明，敲低UCA1在体外和体内均能显著抑制细胞增殖和迁移。此外，RNA测序（RNA-seq）分析显示，敲低UCA1优先影响与细胞增殖、细胞周期和细胞迁移相关的基因。从机制上来说，UCA1通过与EZH2结合抑制p21和Sprouty RTK信号拮抗剂1（SPRY1）的表达，从而促进细胞增殖进程。我们发现UCA1可以介导p21和SPRY1启动子区域H3K27的三甲基化。据我们所知，这是第一份展示UCA1下游靶点在胃癌进展中的整体基因图谱的报告。总的来说，我们的数据揭示了UCA1在胃癌（GC）发生发展中的重要作用。
