Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2.

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

Deubiquitinase PSMD14 enhances hepatocellular carcinoma growth and metastasis by stabilizing GRB2

Abstract(#br)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

HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma

Background: Recent studies reveal that long non-coding RNAs (LncRNAs) play critical roles in the proliferation and migration of human cancer. Previous report has shown that LncRNA HOXA-AS2 was involved in carcinoma processes. However, the expression and biological function of HOXA-AS2 in hepatocellular carcinoma (HCC) are poorly understood. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of HOXA-AS2 in HCC tissues and cell lines. The relation between lncRNA HOXA-AS2 expression and clinicopathological characteristics was assessed by chi-square test. The prognosis was analyzed using Kaplan-Meier method, and compared differences between the two groups by log-rank test. The biological function of HOXA-AS2 on HCC cells were determined both in vitro and in vivo. Results: In the present study, we found that HOXA-AS2 expression was increased in HCC tissues and adjacent normal tissues and high HOXA-AS2 expression was associated with bigger tumor size, advanced tumor stage, and shorter survival time. Knockdown of HOXA-AS2 significantly inhibited HCC cell proliferation and invasion and resulted in an increase of apoptosis. Furthermore, inhibition of HOXA-AS2 in HCC cells significantly repressed tumorigenicity in nude mice. Conclusion: Our results indicated that the inhibition of HOXA-AS2 in HCC cells significantly inhibited cell proliferation in vitro and in vivo, which might provide a potential possibility for targeted therapy of HCC