R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma

: Hepatocellular carcinoma (HCC) is a leading cause of malignant disease-associated mortality, particularly in China. The RSPO2 (R-spondin 2) gene is evolutionarily conserved in vertebrates and is involved in developmental and physiological processes. Importantly, RSPO2 has been reported to be associated with colon cancer and potentiate the Wnt/β-catenin signaling pathway. In the present study, enhanced expression of RSPO2 in HCC was observed using tissue microarray. Similarly, the expression level of RSPO2 was higher in HepG2, Huh7 and Hep3B cells but lower in Bel7404 and QGY7703 cells compared with human normal QSG7701 liver cells. Subsequently, gain-of-function studies indicated that RSPO2 promotes the proliferation and migration of QGY7703 cells based on lentivirus-based gene delivery. Furthermore, it was revealed that p21 and leptin, rather than vascular endothelial growth factor-A, are involved in the function of RSPO2 in QGY7703 cells. Particularly, the signal transducer and activator of transcription 3 (STAT3) and Wnt/β-catenin signaling pathways are involved in this process. Overexpression of RSPO2 resulted in the elevated expression of phosphorylated STAT3, β-catenin and c-Myc. Therefore, the present study is beneficial to the understanding of RSPO2-involved liver cancer transformation and drug discovery.