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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-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 mechanisms of HCC progression through Sharpin overexpression. 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 stably Sharpin-expressing 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87149 | GEO | 2017/01/23

SECONDARY ACCESSION(S): PRJNA343674

REPOSITORIES: GEO

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Project description:Baicalein, a purified flavonoid compound with defined chemical structure extracted from the dry roots of Scutellaria radix that is a broadly used herb in China, has been proved to possess significant anti-hepatoma activity by inhibiting cell proliferation, invasion, metastasis and inducing apoptosis, autophagy via several cancer-related signaling molecules. In recent years, emerging studies have demonstrated that Chinese medicinal herbs can exert their anti-tumor effects through targeting lncRNAs，such as curcumin, camptothecin, resveratrol，paclitaxel. However, there is still no related report about the effects of baicalein on lncRNA expression profile when it exerts its inhibition on hepatoma tumor growth. To investigate whether the antitumor effect of baicalein is related to its modulation of lncRNA expression in hepatocellular carcinoma (HCC), we profiled the lncRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using lncRNA microarray and detected the changes by comparing the lncRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of lncRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations. To investigate whether the antitumor effect of baicalein is related to its modulation of lncRNA expression in hepatocellular carcinoma (HCC), we profiled the miRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using miRNA microarray and detected the changes by comparing the lncRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of lncRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations.

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Sharpin promotes hepatocellular carcinoma progression via transactivation of versican expression

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