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

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

doi:10.1016/j.omtn.2017.06.021

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

Mol Ther Nucleic Acids. 2017 Sep 15:8:291-299. doi: 10.1016/j.omtn.2017.06.021. Epub 2017 Jul 3.

Authors

Huazhang Wu¹, Ying Hu², Xiufang Liu², Wei Song², Pihai Gong², Kun Zhang³, Zhenxing Chen⁴, Menghan Zhou², Xiaohui Shen², Yanyan Qian², Hong Fan⁵

Affiliations

¹ 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.
² 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.
³ Third Affiliated Hospital of Harbin Medical University (Harbin Medical University Cancer Hospital), Harbin 150040, China.
⁴ Department of Pathophysiology, Medical School of Southeast University, Nanjing 210009, China.
⁵ 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. Electronic address: fanh@seu.edu.cn.

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.

Keywords: CDH1; SNAI1; TRERNA1; gastric cancer; metastasis.