Identification of NPAC as a novel biomarker and regulator for hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) has a high morbidity and mortality around the world, yet the effective therapeutic option for HCC is still limited. NPAC, also known as glyoxylate reductase 1 homolog, is a new nuclear protein recently implicated in tumor biology. However, the role of NPAC in HCC remains unclear. The present study aimed to evaluate the clinical significance and potential role of NPAC in HCC. The NPAC expression in HCC tissues and matched adjacent normal tissues was detected by real-time polymerase chain reaction, immunohistochemistry (IHC), and Western blot analysis. The clinical significance of the expression of NPAC in HCC was assessed by the Kaplan-Meier survival curve and the Cox regression model. In addition, we established a doxiline-induced overexpression of the NPAC system. The effects of NPAC on HCC cell proliferation, migration, and apoptosis were checked by CCK-8 proliferation assays, transwell, and flow cytometry, respectively. The NPAC expression was significantly downregulated in HCC tissues and HCC cell lines. NPAC reduction was significantly correlated with poorer survival among patients with HCC, and the multivariate analysis confirmed its independent prognostic value. Furthermore, overexpression of NPAC dramatically suppressed the proliferation of HCC cells and promoted HCC cells apoptosis. Besides, the levels of phosphorylation of janus kinase 2 (JAK2) and signal transduction and activator 3 (STAT3) were significantly reduced after overexpression of NPAC in HCC cell lines. These results suggest that NPAC may play an important role in the development and progression of HCC, and can act as a novel potential prognostic biomarker and therapeutic target for HCC.