HIF-1α-regulated Galectin-3 affords the vasculogenic mimicry and poor prognosis of hepatocellular carcinoma

In present study, we explore the role of HIF-1α-regulated Galectin-3 in VM and poor prognosis of HCC as well as the potential regulatory mechanism. Immunohistochemistry method was used to evaluate HIF-1α and CD31/PAS expression in HCC patients. Vitro experiments were conducted to reveal the molecular mechanisms that regulate Galectin-3 expression under hypoxia. Moreover, the effects of Galectin-3 on the biological function of HCC cells were investigated using MTS kit, wound-healing assay, cell transwell assay, flow cytometry assay and three-dimensional culture under hypoxia. HIF-1α expressions were significantly higher in HCC tissues than those in adjacent hepatic tissues in cirrhosis-free patients with HCC ( P  = 0.023). The patients with positive-HIF-1α expression had worse overall survival ( P  = 0.002). HIF-1α was positively correlated with Galectin-3 in HCC tumor tissues ( P  < 0.05). Higher expression of Galectin-3 linked to poor overall survival ( P  = 0.002). HIF-1α and Galectin-3 were correlated with VM of HCC ( P  < 0.05). Hypoxia promotes proliferation, migration, invasion and VM formation of HCC cells, and suppresses to apoptosis ( P  < 0.05). Galectin-3 is the target genes of HIF-1α transcription factor. Silencing Galectin-3 abolished effect of hypoxia microenvironment on the function of HCC cells. In conclusion, HIF-1α-regulated Galectin-3 contributes to the vasculogenic mimicry and poor prognosis of HCC.