Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343674 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2017-01-23 | GSE87149 | GEO
Project description:Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer mortality worldwide. Further improvements are needed for the treatment of CRC. The E3 ubiquitin ligase is an enzyme that plays an important role in regulating protein expression levels via posttranslational ubiquitin-mediated proteolysis, and it is reportedly involved in the progression of various cancers, making it a target of recent interest in anticancer therapy. In this study, using comprehensive expression analysis involving spatial transcriptomic analysis with single-cell RNA sequencing in clinical CRC datasets, we identified the ubiquitin-associated protein Shank-associated RH domain interactor (SHARPIN) as a putative driver gene located on amplified chromosome 8q. SHARPIN was overexpressed in tumor cells, and high expression of SHARPIN in tumor tissues was positively correlated with lymphatic invasion and was independently predictive of a poor prognosis in CRC patients. In vitro and in vivo analyses using SHARPIN-overexpressing or -knockout CRC cells revealed that SHARPIN upregulated MDM2, resulting in subsequent downregulation of p53, which inhibits tumor cell apoptosis and promotes tumor growth in CRC. Furthermore, SHARPIN overexpression and significant effects on survival were observed in various cancers. In conclusion, SHARPIN is a novel driver gene that potentially promotes tumor growth following apoptosis inhibition in part by inhibiting p53 expression via MDM2 upregulation; therefore, SHARPIN represents a potential therapeutic target for CRC.
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Project description:Versican has been reported to participate in carcinogenesis in several malignant tumors. However, the accurate role of Versican in hepatocellular carcinoma (HCC) remains an enigma. Our current study reveals that VersicanV1, a predominant isoform of Versican in liver, is significantly unregulated in HCC tissues and correlates with poor prognosis. Both in vitro and in vivo experiments show that knockdown of VersicanV1 in HCC cells attenuates cancer cells malignancy. Further studies identify the positive role of VersicanV1 in aerobic glycolysis. Mechanistic investigation discovers the activation of EGFR-PI3K-AKT pathway in HCC cells expressing high VersicanV1. Moreover, EGF-like motif is indispensable for VersicanV1 to promote Warburg effect of HCC cells and subsequently, proliferation, invasion and metastasis ability via activation of EGFR-PI3K-AKT axis. Taken together, our research highlights a novel role of VersicanV1 in the progression of HCC, suggesting that VersicanV1 is an indicator for prognosis and a potential therapeutic target of HCC.
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Project description:Massive studies have been applied in exploring the factors driving pathogenesis, progression and metastasis of hepatocellular carcinoma. However these studies were inefficient in disclosing the fundamental mechanism which promotes hepatocellular carcinoma. Zinc and zinc-finger proteins have been important in extensive biological processes for human. Supervised machine learning using bootstrapping algorithm on GEO and TCGA transcriptome data for hepatocellular carcinoma identified zinc-finger like protein ZFPL1 as potential hepatocellular carcinoma driver. Further studies validated ZFPL1 significantly promoted progression and metastasis of hepatocellular carcinoma. We performed RNA-seq on si-ZFPL1 xenograft tissue and identified CLDN3 as potential target gene for ZFPL1. Further experiments confirmed interaction between ZFPL1 and WNT signaling pathway markers. Conclusively, these studies indicated the effect and mechanism of ZFPL1 on promoting progression and metastasis of hepatocellular carcinoma and might gap the bridge between zinc-finger like proteins and hepatocellular carcinoma.
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