Dataset Information

Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.

ABSTRACT: Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-?B signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here we report novel mechanisms of HCC progression through Sharpin overexpression. In our study, Sharpin was upregulated in human HCC tissues. Increased Sharpin expression enhanced hepatoma cell invasion, whereas decrease in Sharpin expression by RNA interference inhibited invasion. Microarray analysis identified that Versican, a chondroitin sulfate proteoglycan that plays crucial roles in tumor progression and invasion, was also upregulated in Sharpin-expressing stable cells. Versican expression increased in the majority of HCC tissues and knocking down of Versican greatly attenuated hepatoma cell invasion. Sharpin expression resulted in a significant induction of Versican transcription synergistically with Wnt/?-catenin pathway activation. Furthermore, Sharpin-overexpressing cells had high tumorigenic properties in vivo. These results demonstrate that Sharpin promotes Versican expression synergistically with the Wnt/?-catenin pathway, potentially contributing to HCC development. A Sharpin/Versican axis could be an attractive therapeutic target for this currently untreatable cancer.

SUBMITTER: Tanaka Y

PROVIDER: S-EPMC5177774 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.

Tanaka Y Y Tateishi K K Nakatsuka T T Kudo Y Y Takahashi R R Miyabayashi K K Yamamoto K K Asaoka Y Y Ijichi H H Tateishi R R Shibahara J J Fukayama M M Ishizawa T T Hasegawa K K Kokudo N N Koike K K

Oncogenesis 20161212 12

Sharpin (Shank-associated RH domain-interacting protein, also known as SIPL1) is a multifunctional molecule that participates in various biological settings, including nuclear factor-κB signaling activation and tumor suppressor gene inhibition. Sharpin is upregulated in various types of cancers, including hepatocellular carcinoma (HCC), and is implicated in tumor progression. However, the exact roles of Sharpin in tumorigenesis and tumor progression remain largely unknown. Here we report novel m ...[more]

PMID: 27941932

Similar Datasets

Project description:BackgroundForkhead box M1 (FOXM1) is a proliferation-associated transcription factor of the forkhead box proteins superfamily, which includes four isoforms FOXM1a, b, c, and d. FOXM1 has been implicated in hepatocellular carcinoma (HCC) progression, but the underlying molecular mechanism remains elusive. In this study, we aim to clarify the molecular basis for FOXM1-mediated HCC progression.MethodsBioinformatic analysis was used to explore the differentially expressed genes predicting HCC proliferation. The expression of FOXM1 and kinesin family member (KIF)4A was confirmed by western blotting and immunohistochemistry in HCC tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of FOXM1 and KIF4A on HCC. The effect of FOXM1 on the regulation of KIF4A expression was studied in cell biology experiments. The interaction between KIF4A and FOXM1 was analyzed by chromatin immunoprecipitation and luciferase experiments. A series of experiments was performed to explore the functions of FOXM1/KIF4A in HCC progression, such as cell proliferation, cell growth, cell viability, and cell cycle. A xenograft mouse model was used to explore the regulatory effect of FOXM1-KIF4A axis on HCC tumor growth.ResultsFOXM1 and KIF4A were overexpressed in human primary HCC tissues compared to that in matched adjacent normal liver tissue and are significant risk factors for HCC recurrence and shorter survival. We found that KIF4A was dominantly regulated by FOXM1c among the four isoforms, and further identified KIF4A as a direct downstream target of FOXM1c. Inhibiting FOXM1 decreased KIF4A expression in HCC cells, whereas its overexpression had the opposite effect. FOXM1-induced HCC cell proliferation was dependent on elevated KIF4A expression as KIF4A knockdown abolished FOXM1-induced proliferation of HCC cells both in vitro and in vivo.ConclusionThe FOXM1-KIF4A axis mediates human HCC progression and is a potential therapeutic target for HCC treatment.

Dataset Information

Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.

Publications

Sharpin promotes hepatocellular carcinoma progression via transactivation of Versican expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets