LncRNA TRERNA1 facilitates hepatocellular carcinoma metastasis by dimethylating H3K9 in the CDH1 promoter region via the recruitment of the EHMT2/SNAI1 complex.

OBJECTIVES:Long non-coding RNAs (LncRNAs) play an important role in hepatocellular carcinoma development, however, as a crucial driver of hepatocellular carcinoma (HCC) metastasis, their functions in tumour metastasis remain largely unknown. MATERIALS AND METHODS:The lncRNA expression levels were detected in HCC by quantitative real-time PCR (qPCR). The function of Tduanyu1795NA1 was examined by wound-healing assays, transwell assays and tail vein injection experiments. The potential regulatory mechanisms of Tduanyu1795NA1 on its target genes were explored by ChIP, RIP, IP and WB assays. RESULTS:Elevated Tduanyu1795NA1 levels promoted HCC cell migration and invasion in vitro and in vivo. Tduanyu1795NA1 recruited EHMT2 to dimethylate H3K9 in the CDH1 promoter region. Furthermore, EHMT2 bound to SNAI1 to suppress CDH1 expression in HCC cells. After inhibiting the expression level of CDH1 was restored and was involved in the regulation of the EHMT2/SNAI1 complex. The level of Tduanyu1795NA1 was positively correlated with tumour metastasis and was negatively correlated with the expression of CDH1 in HCC tissues. CONCLUSIONS:For the first time, the current study reveals that Tduanyu1795NA1 promotes cell metastasis and the invasion of HCC via the recruitment of EHMT2 and/or the EHMT2/SNAI1 complex to suppress CDH1. These data identify a novel mechanism that regulates Tduanyu1795NA1 in metastatic HCC and provides a potential targeted therapy for HCC patients.

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