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Abstract
<p class="first" id="d2602233e174">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 suggest that PSMD14
could serve as a novel promising therapeutic candidate for HCC.
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