Nucleostemin promotes hepatocellular carcinoma by regulating the function of STAT3.

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor in the liver and the second leading cause of cancer-related death worldwide. The collaborative function between Nucleostemin (NS) and STAT3 has been reported but not well studied in HCC. Here, we found a significant correlation between NS expression and STAT3 phosphorylation, not only in HCC cancers but also in HCC tissues. Patients with high expression of both NS and p-STAT3 show a very poor survival rate. High expression of both NS and p-STAT3 is also associated with tumor size and microvascular invasion. Knocking down the expression of NS greatly reduces the phosphorylation of STAT3. Conversely, overexpression of NS significantly promotes STAT3 phosphorylation. NS and p-STAT3 are located in the nucleus and physiologically interact with each other. Furthermore, NS greatly enhances cell migration and invasion by promoting the epithelial-mesenchymal transition (EMT). NS also supports cell proliferation and colony formation. The importance of NS in HCC was further demonstrated by evaluating tumor formation in vivo. Therefore, we demonstrate a critical collaborative function between NS and STAT3 in HCC, providing an invaluable insight into the mechanism of HCC. The concomitant expression of NS and p-STAT3 might be a potential prognostic indicator and therapeutic target in patients with HCC.