Background and Aims: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in clinical practice. Invasion, metastasis and postoperative recurrence are the main causes of death for HCC patients. At present, the dysregulation of long non-coding RNAs (lncRNA) is considered to be related to the occurrence and metastasis of various cancers. Studies have showed that lncRNA SNHG12 expression is increased in HCC tissue, but its specific function is still unclear. Therefore, this study was conducted to investigate the action of lncRNA SNHG12 in HCC cells and the mechanism. 
Methods: The gene expressions of SNHG12 as well as the predicted targeted miRNA and gene (miR-199a-5p and FZD6) in HCC cell lines HepG2 and human intrahepatic bile duct cell line HIBEC were detected by qRT-PCR method. The effects of down-regulation of SNHG12 on the proliferation, invasion and the expressions of proteins associated with epithelial-mesenchymal transition (EMT) in HepG2 cells were observed. The association between SNHG12 and miR-199a-5p was analyzed by miRanda and Dual luciferase reporter gene assay, and then, the effects of down-regulation of miR-199a-5p on the proliferation, invasion and EMT in HepG2 cells as well as the influences of SNHG12 exerted by miR-199a-5p were analyzed. The relationship between miR-199a-5p and FZD6 was analyzed by the TargetScan and Dual luciferase reporter gene assay, and then, the effects of up-regulation and down-regulation of FZD6 on the proliferation, invasion and EMT in HepG2 cells as well as the effects of SNHG12 and miR-199a-5p on FZD6 expression were detected.
Results: The expression level of SNHG12 was significantly increased, miR-199a-5p was significantly decreased and FZD6 was significantly increased in HepG2 cells compared with those in HIBEC cells (all P<0.01). In HepG2 cells, the proliferation, invasion and EMT were significantly inhibited after down-regulation of SNHG12, while its overexpression resulted in opposite effects (all P<0.05). The 3'UTR of SNHG12 was targeted by miR-199a-5p. The proliferation, invasion and EMT of HepG2 cells were augmented by down-regulation of miR-199a-5p, and were suppressed by its overexpression (all P<0.05). The effects of miR-199a-5p overexpression on HepG2 cells were partially reversed by the simultaneous overexpression of SNHG12 (all P<0.05). The miR-199a-5p were targeted by FZD6. The proliferation, invasion and EMT of HepG2 cells were inhibited by down-regulation of FZD6, while were increased by up-regulation of FZD6 (all P<0.05). Down-regulation of SNHG12 inhibited FZD6 gene and protein expressions, while down-regulation of miR-199a-5p promoted FZD6 expression (all P<0.01). Compared with down-regulation of miR-199a-5p alone, the FZD6 expression was significantly decreased by both SNHG12 and miR-199a-5p down-regulations (P<0.01).
Conclusion: Upregulation of lncRNA SNHG12 in HCC cells can promote the proliferation, invasion and EMT process of HCC cells through influencing the miR-199a-5p/FZD6 axis.