A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma

BACKGROUND: To understand the involvement of structural maintenance of chromosome 4 (SMC4) in the development and progression of hepatocellular carcinoma (HCC). METHODS: Real-time quantitative PCR and Western Blotting were applied to measure the expression of SMC4 in HCC samples and cell lines. The tumor-promoting effect of SMC4 was determined by WST-1, soft agar colony formation, cell motility and invasion assays. The SMC4 target signal pathway was identified by luciferase reporter and real-time quantitative PCR assays. RESULTS: The upregulation of SMC4 was frequently detected in HCC samples and cell lines. Functional assays demonstrated that SMC4 could effectively promote tumor cell growth rate, colony formation in soft agar, wound-healing and invasion. Further studies showed that increased miR-219 levels caused a significant decrease in the SMC4 expression, and SMC4 inhibitor downregulated JAK2/Stat3 expression at both the mRNA and protein levels. CONCLUSIONS: Our findings provide new insight into SMC4 function and the mechanisms of growth and invasion of HCC.