Wu Huazhang, Hu Ying, Liu Xiufang, Song Wei, Gong Pihai, Zhang Kun, Chen Zhenxing, Zhou Menghan, Shen Xiaohui, Qian Yanyan, Fan Hong
Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, China; School of Life Science, Bengbu Medical College, Bengbu 233030, China.
Department of Medical Genetics and Developmental Biology, Medical School of Southeast University, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing 210009, China.
Mol Ther Nucleic Acids. 2017 Sep 15;8:291-299. doi: 10.1016/j.omtn.2017.06.021. Epub 2017 Jul 3.
Long noncoding RNA (lncRNA) has been implicated in cancer, but little is known about the role of lncRNAs as regulators of tumor metastasis. In the present study, we demonstrate that lncRNA TRERNA1 acts like an enhancer of SNAI1 to promote cell invasion and migration and to contribute to metastasis of gastric cancer (GC). TRERNA1 is significantly unregulated in GCs and GC cell lines. Increased TRERNA1 is positively correlated with lymph node metastasis of GCs. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays revealed that TRERNA1 functions as a scaffold to recruit EZH2 to epigenetically silence epithelial-mesenchymal transition marker CDH1 by H3K27me3 of its promoter region. TRERNA1 knockdown markedly reduced GC cell migration, invasion, tumorigenicity, and metastasis. Depletion of TRERNA1 reduced cell metastasis of GCs in vivo. Taken together, our findings indicated that TRERNA1 serves as a critical effector in GC progression by regulating CDH1 at the transcription level. It is implied that TRERNA1/CDH1 is a new potential target for GC therapy.
长链非编码RNA(lncRNA)与癌症相关,但lncRNA作为肿瘤转移调节因子的作用却知之甚少。在本研究中,我们证明lncRNA TRERNA1作为SNAI1的增强子,促进细胞侵袭和迁移,并促进胃癌(GC)转移。TRERNA1在GC组织和GC细胞系中显著上调。TRERNA1表达增加与GC的淋巴结转移呈正相关。RNA免疫沉淀(RIP)和染色质免疫沉淀(ChIP)分析表明,TRERNA1作为支架招募EZH2,通过其启动子区域的H3K27me3使上皮-间质转化标志物CDH1发生表观遗传沉默。敲低TRERNA1显著降低了GC细胞的迁移、侵袭、致瘤性和转移能力。在体内,TRERNA1的缺失减少了GC细胞的转移。综上所述,我们的研究结果表明,TRERNA1通过在转录水平调节CDH1,在GC进展中起关键作用。这意味着TRERNA1/CDH1是GC治疗的一个新的潜在靶点。