NUP205 Stabilized YAP1 Protein to Stimulate Growth of Hepatocellular Carcinoma Cells in vitro and in vivo.

[PURPOSE] Targeted therapy for hepatocellular carcinoma (HCC) is limited by drug resistance and other constraints, leaving treatments sub-optimal and making identification of new target genes urgent. Nuclear pore protein 205 (NUP205) is highly expressed in HCC and associated with poor prognosis but mechanisms of action remain unclear. The current study investigated functions of NUP205 in HCC.

[METHODS] Bioinformatics analyses of NUP205 expression in HCC samples from The Cancer Genome Atlas, Gene Expression Omnibus and Kaplan-Meier databases were conducted. Proliferation and apoptosis were measured in HCC LM3 and SK-Hep1 cells with NUP205 knockdown and overexpression and growth of HCC xenografts in a nude mouse model. The stability of Yes-associated protein (YAP1) mRNA and protein in cells with NUP205 knockdown and overexpression was assessed.

[RESULTS] NUP205 was overexpressed in HCC tissues and expression correlated with pathological grade and prognosis. NUP205 knockdown in vitro inhibited cell proliferation 2-3-fold, induced apoptosis 4-5-fold and suppressed in vivo tumor growth by 40%. Opposing effects were found for NUP205 overexpression. NUP205 acted via the ubiquitin-proteasome pathway to stabilize YAP1 protein.

[CONCLUSION] NUP205 stabilizes YAP1 and may be considered to act as an HCC oncogene. The NUP205-YAP1 axis may be a therapeutic target.