LncRNA TRERNA1 Function as an Enhancer of SNAI1 Promotes Gastric Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition

LncRNA TRERNA1作为SNAI1的增强子通过调节上皮-间质转化促进胃癌转移

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作者:Huazhang Wu, Ying Hu, Xiufang Liu, Wei Song, Pihai Gong, Kun Zhang, Zhenxing Chen, Menghan Zhou, Xiaohui Shen, Yanyan Qian, Hong Fan

Abstract

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.

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