Oct 22, 2019

Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2

Cancer Letters
Jie LvZhenyu Yin

Abstract

Hepatocellular carcinoma (HCC) has emerged as one of the most common malignancies worldwide. It is associated with a high mortality rate, as evident from its increasing incidence and extremely poor prognosis. The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMD14 in HCC progression and the underlying mechanisms. We found that PSMD14 was significantly upregulated in HCC tissues. Overexpression of PSMD14 correlated with vascular invasion, tumor number, tumor recurrence, and poor tumor-free and overall survival of patients with HCC. Knockdown and overexpression experiments demonstrated that PSMD14 promoted proliferation, migration, and invasion in HCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, we identified PSMD14 as a novel post-translational regulator of GRB2. PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells. Furthermore, pharmacological inhibition of PSMD14 with O-phenanthroline (OPA) suppressed the malignant behavior of HCC cells in vitro and in vivo. In conclusion, our findings sug...Continue Reading

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Mentioned in this Paper

Study
In Vivo
Gene Knockdown Techniques
Liver Carcinoma
Neoplasms
Recurrent Tumor
Cell Proliferation
PSMD14
GRB2 gene
PSMD14 protein, human

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