SHARPIN regulates the development of clear cell renal cell carcinoma by promoting von Hippel‐Lindau protein ubiquitination and degradation

Yin, Rusha; Liu, Shuai

doi:10.1111/cas.15096

Cited by 8 publications

(10 citation statements)

References 48 publications

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Section: Discussionmentioning

confidence: 97%

“…Moreover, KEGG analysis was mainly concentrated on protein digestion and absorption, the cAMP signaling pathway, the calcium signaling pathway, and the Ras signaling pathway. The abnormal function of protein digestion and absorption following NPEPL1 expression dysregulation promoted invasion, migration, and drug resistance in ccRCC [ 35 , 36 ]. With the in-depth understanding of the mechanism of ccRCC development, cAMP and the Ras signaling pathway played a crucial role in regulating biological behaviors [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma

Wei¹,

Zhou

et al. 2023

Journal of Oncology

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Aminopeptidase-like 1 (NPEPL1) is a member of the aminopeptidase group that plays a role in the development and progression of various diseases. Expression of NPEPL1 has been reported to be involved in prostate, breast, and colorectal cancers. However, the role and mechanism of NPEPL1 in clear cell renal cell carcinoma (ccRCC) are unclear. The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases were used to predict the relationship between clinicopathological features and NPEPL1 expression. Changes in immune status and drug sensitivity with NPEPL1 expression were analyzed by the “CIBERSORT” function in R software. The results found that NPEPL1 expression was upregulated in ccRCC tissues, with expression progressively increasing with ccRCC stage and grade. Patients with high NPEPL1 expression presented with a poor prognosis across different clinicopathological features. Univariate and multivariate Cox regression analyses indicated that aberrant NPEPL1 expression was an independent risk factor for ccRCC. The nomogram showed that NPEPL1 expression improved the accuracy of predicting the prognosis of ccRCC patients. The Gene Ontology (GO) term enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that NPEPL1 may be involved in the development of ccRCC through the voltage-gated calcium channel complex, channel activity, cAMP signaling pathway, and oxytocin signaling pathway. The coexpression analysis found that NPEPL1 altered tumor characteristics by interacting with related genes. The “CIBERSORT” analysis showed that elevated NPEPL1 expression was followed by an enrichment of regulatory T cells and follicular helper T cells in the microenvironment. The drug sensitivity analysis found patients with high NPEPL1 expression had a higher benefit from axitinib, cisplatin, and GSK429286A. In conclusion, upregulation of NPEPL1 expression was involved in ccRCC prognosis and treatment. NPEPL1 could be used as a therapeutic target to guide clinical dosing.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma

Wei¹,

Zhou

et al. 2023

Journal of Oncology

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“…Alternatively, overexpression of SHARPIN in Chinese hamster ovarian cells can promote cell migration and cell proliferation ( 25 ). At present, several gene expression analyses targeting tumor biopsy tissue are underway, and the human SHARPIN gene is upregulated in tumorigenesis in various human cancers such as breast cancer, esophageal cancer and renal cell carcinoma ( Table 1 ) ( 96 – 98 ).…”

Section: The Pathophysiological Functions Of Sharpinmentioning

confidence: 99%

“…Overexpression of SHARPIN leads to elevated intracellular HIF2α in patients with Renal cell carcinoma. SHARPIN can promote polyubiquitination of pVHL and thus degradation by the proteasome, which causes HIF-2α to escape the fate of ubiquitination and successfully transfer into the nucleus to control gene expression ( 98 ). Therefore, SHARPIN promotes the development of renal cell carcinoma via enhancing the degradation of the tumor suppressor pVHL.…”

Section: The Pathophysiological Functions Of Sharpinmentioning

confidence: 99%

Advances in the Structural and Physiological Functions of SHARPIN

Wang

2022

Front. Immunol.

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SHARPIN was initially found as a SHANK-associated protein. SHARPIN can be used as an important component to form the linear ubiquitin chain assembly complex (LUBAC) with HOIL-1L, HOIP to produce a linear ubiquitin chain connected N-terminal Met1, playing a critical role in various cellular processes including NF-κB signaling, inflammation, embryogenesis and apoptosis. SHARPIN alone can also participate in many critical physiological activities and cause various disorders such as chronic dermatitis, tumor, and Alzheimer’s disease. Mice with spontaneous autosomal recessive mutations in the SHARPIN protein mainly exhibit chronic dermatitis and immunodeficiency with elevated IgM. Additionally, SHARPIN alone also plays a key role in various cellular events, such as B cells activation and platelet aggregation. Structural studies of the SHARPIN or LUBAC have been reported continuously, advancing our understanding of it at the molecular level. However, the full-length structure of the SHARPIN or LUBAC was lagging, and the molecular mechanism underlying these physiological processes is also unclear. Herein, we summarized the currently resolved structure of SHARPIN as well as the emerging physiological role of SHARPIN alone or in LUBAC. Further structural and functional study of SHARPIN will provide insight into the role and underlying mechanism of SHARPIN in disease, as well as its potential application in therapeutic.

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“…Previous studies have shown that the LUBAC contributes to the regulation of numerous physiological and pathological processes, such as inflammation [ 4 ], autoimmunity [ 5 – 7 ], and the cell cycle [ 8 ], which are relevant to cancer progression. The LUBAC plays important roles in cancer development and progression, including those of prostate [ 9 ], renal [ 10 ], and breast cancers [ 11 ]. A previous study reported that SHARPIN facilitates HCC development [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

RBCK1 promotes hepatocellular carcinoma metastasis and growth by stabilizing RNF31

Chen

Zhao

et al. 2022

Cell Death Discov.

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RNF31 (HOIP), RBCK1 (HOIL-1L), and SHARPIN are subunits of the linear ubiquitin chain assembly complex. Their function and specific molecular mechanisms in hepatocellular carcinoma (HCC) have not been reported previously. Here, we investigated the role of RNF31 and RBCK1 in HCC. We showed that RNF31 and RBCK1 were overexpressed in HCC and that upregulation of RNF31 and RBCK1 indicated poor clinical outcomes in patients with HCC. RNF31 overexpression was significantly associated with more satellite foci and vascular invasion in patients with HCC. Additionally, RBCK1 expression correlated positively with RNF31 expression in HCC tissues. Functionally, RBCK1 and RNF31 promote the metastasis and growth of HCC cells. Moreover, the RNF31 inhibitor gliotoxin inhibited the malignant behavior of HCC cells. Mechanistically, RBCK1 interacted with RNF31 and repressed its ubiquitination and proteasomal degradation. In summary, the present study revealed an oncogenic role and regulatory relationship between RBCK1 and RNF31 in facilitating proliferation and metastasis in HCC, suggesting that they are potential prognostic markers and therapeutic targets for HCC.

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SHARPIN regulates the development of clear cell renal cell carcinoma by promoting von Hippel‐Lindau protein ubiquitination and degradation

Cited by 8 publications

References 48 publications

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma

Comprehensive Analysis of Transcriptomic Profiles Identified the Prediction of Prognosis and Drug Sensitivity of Aminopeptidase-Like 1 (NPEPL1) for Clear Cell Renal Cell Carcinoma

Advances in the Structural and Physiological Functions of SHARPIN

RBCK1 promotes hepatocellular carcinoma metastasis and growth by stabilizing RNF31

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