The Mechanism of Long Non-Coding RNA Plasmacytoma Variant Translocation 1 Regulating Hepatoma Cells Proliferation and Apoptosis-Targeting the Transcription Factor Lymphoid Enhancer-Binding Factor 1 to Promote the Expression of Downstream Baculoviral IAP Repeat Containing 5

Long non-coding RNA (lncRNA) PVT1 has been reported to be involved in the development of hepatocellular carcinoma (HCC). The expression of anti-apoptosis protein baculoviral IAP repeat containing 5 (BIRC5) is also increased in hepatoma cells and can be activated by lymphoid enhancer binding factor 1 (LEF1), which is one of the potential markers for HCC. The objective of this study is to explore the relationship between PVT1, BIRC5, and LEF1, so as to uncover the pathways and mechanisms of PVT1 promoting HCC. BIRC5 and PVT1 expression in normal liver cells and hepatoma cells was analyzed by RT-qPCR and western blotting. PVT1 short hairpin (sh)-RNA plasmids were transfected into PLC/PRF5 hepatoma cells to knockdown PVT1 expression, and then cell proliferation, colony formation, apoptosis and expression of related proteins were assessed. Besides, the interaction between PVT1 and miR-409-5p together with LEF1 and miR-409-5p was detected by dual luciferase assay. Results showed that the expression of BIRC5 and PVT1 were significantly increased in hepatoma cells and was highest in PLC/PRF5 compared with other hepatoma cells. Knockdown of PVT1 obviously reduced the ability of PLC/PRF5 cell proliferation and colony formation, whereas enhanced cell apoptosis. The protein expression of BIRC5 and LEF1 was also decreased after PVT1 was knockdown. Moreover, miR- 409-5p level was increased after PVT1 silencing and it can interact with both PVT1 and LEF1. In conclusion, lncRNA PVT1 may exert its accelerative effect on HCC by targeting LEF1 in Hippo signaling pathway through miR-409-5p, thereby enhancing the expression of apoptosis inhibitor BIRC5.