Integrated analysis identified NPNT as a potential key regulator in tumor metastasis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the lethal malignancies worldwide. Tumor metastasis is the main cause of HCC related death. Although progress has been made in the mechanism study of HCC in the past decades, the underlying mechanism of HCC metastasis has not been fully illustrated. In the present study, bioinformatic analysis including weighted gene co-expression network analysis (WGCNA), differentially expressed gene analysis, and gene enrichment analysis were applied to discover genes correlated with HCC metastasis. Immunohistochemistry (IHC) assays were applied to detect the expression of NPNT in HCC samples. Cell transfection, wound healing, matrigel transwell assays, and western blot assays were utilized to evaluate the effects of NPNT on cell migration and invasion and signaling pathway variation. We found that NPNT was up-regulated in HCC tumor tissues compared with normal tissues. Especially, NPNT was highly expressed in metastatic tumor compared with non-metastatic HCC tumors. Down-regulation of NPNT via siRNA transfection inhibited cell migration, invasion, and FAK/PI3K/AKT signaling pathway in HCC. Our results demonstrate that NPNT is a potential key regulator in HCC metastasis.