SOX12 upregulation is associated with metastasis of hepatocellular carcinoma and increases CDK4 and IGF2BP1 expression.

OBJECTIVE

In this study, we studied the expression profile of SOX12 gene in different pathological stages of hepatocellular carcinoma (HCC) and explored the possible downstream genes related to its regulation of HCC invasion and migration.

MATERIALS AND METHODS

Bioinformatic data mining was performed in liver cancer cohort in TCGA. HepG2 cells were used as in vitro cell model to assess the effect of SOX12 on CDK4 and IGF2BP1 expression. The association between the expression of SOX12, CDK4 or IGF2BP1 and survival time in HCC patients was also assessed based on the data in TCGA.

RESULTS

The regional lymph node metastasis (N1) and distant metastasis (M1) cases had significantly increased SOX12 expression than the lymph node negative (N0) and distant metastasis negative (M0) cases respectively. CDK4 and IGF2BP1 were among the top 20 SOX12 co-upregulated genes in HCC, which have well characterized enhancing the effect on HCC cell growth, invasion, and metastasis. In HepG2 cells, knockdown of SOX12 reduced IGF2BP1 and CDK4 expression, while enforced SOX12 expression significantly enhanced their expression. Low SOX12 or CDK4 expression was associated with significantly better 3-year survival and better 5-year survival. Low IGF2BP1 expression was associated with significantly better 3-year survival in HCC patients.

CONCLUSIONS

SOX12 upregulation is associated with regional and distant metastasis of HCC. SOX12 can increase the expression of CDK4 and IGF2BP1, which confer malignant phenotypes to HCC. The expression of SOX12, IGF2BP1 or CDK4 might be potential clinical prognostic markers for HCC.