NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4

Butt, Ghazala; Yaylım, İlhan; Attar, Rukset; Aras, Aliye; Romero, Mirna Azalea; Qureshi, Muhammad Zahid; Purenović, Jelena; Farooqı, Ammad Ahmad

doi:10.1007/978-3-030-20301-6_19

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…WWP1 is frequently upregulated in multiple human malignancies, and has been found to play an important role in cell proliferation, apoptosis and invasion (Nourashrafeddin et al, 2015;Zhi & Chen, 2012;Chen et al, 2007a;Chen et al, 2007b;Chen & Zhang, 2018). WWP2 functions as an oncogene in liver cancer, breast cancer, endometrial cancer, gastric cancer, lung cancer, oral cancer, and ovarian cancer (Clements et al, 2015;Fang et al, 2020;Fukumoto et al, 2014;Jung et al, 2014;Butt et al, 2019;Sakashita et al, 2013;Wan et al, 2019). The expression of NEDL1 in benign neuroblastoma is higher than that in non-malignant neuroblastoma (Li et al, 2008a;Li et al, 2008b).…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer

Zhao

Mao

et al. 2021

PeerJ

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The members of the Nedd4-like E3 family participate in various biological processes. However, their role in clear cell renal cell carcinoma (ccRCC) is not clear. This study systematically analyzed the Nedd4-like E3 family members in ccRCC data sets from multiple publicly available databases. NEDD4L was identified as the only NEDD4 family member differentially expressed in ccRCC compared with normal samples. Bioinformatics tools were used to characterize the function of NEDD4L in ccRCC. It indicated that NEDD4L might regulate cellular energy metabolism by co-expression analysis, and subsequent gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A prognostic model developed by the LASSO Cox regression method showed a relatively good predictive value in training and testing data sets. The result revealed that NEDD4L was associated with biosynthesis and metabolism of ccRCC. Since NEDD4L is downregulated and dysregulation of metabolism is involved in tumor progression, NEDD4L might be a potential therapeutic target in ccRCC.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer

Zhao

Mao

et al. 2021

PeerJ

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“…For example, NEDD4 participates in cell migration in lung cancer through mediating EGFR signaling (20). NEDD4 mediates the reduction of CX43 regulated by fulvestrant in breast cancer cells (21). There are also studies demonstrating the regulatory role of NEDD4 in some of the symptoms of AS.…”

Section: Discussionmentioning

confidence: 99%

NEDD4 attenuates oxidized low‑density lipoprotein‑induced inflammation and dysfunction in vascular endothelial cells via regulating APEX1 expression

Tan

et al. 2023

Exp Ther Med

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Atherosclerosis chiefly results from inflammation as well as vascular endothelial cell dysfunction. Methylation levels of neuronally expressed developmentally downregulated 4 (NEDD4) were found to be fortified in atherosclerosis patients and NEDD4 deficiency enhanced vascular calcification. However, the exact function of NEDD4 in inflammation and vascular endothelial dysfunction remains to be elucidated. In the present study, CCK-8 assay was used to estimate cell viability. Reverse transcription-quantitative PCR was adopted to examine the expression of NEDD4, inflammation-associated enzymes and apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1). Western blotting was used to test NEDD4, endothelial nitric oxide synthase, inducible nitric oxide synthase and APEX1 protein levels. Cytotoxicity was detected by a lactate dehydrogenase (LDH) kit. Reactive oxygen species level was tested by a corresponding kit. Vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 contents were examined with ELISA. Cell adhesion assays evaluated the adhesion of endothelial cells. Co-immunoprecipitation assay was used to test the relationship between NEDD4 and APEX1. The data revealed that NEDD4 expression rapidly declined in oxidized low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs). Following NEDD4 overexpression, the active damage, inflammatory release and endothelial cell dysfunction in ox-LDL-induced HUVECs were attenuated. After co-transfection of APEX1 interference plasmids and NEDD4 overexpression plasmids, cell damage, inflammatory release and endothelial cell dysfunction in ox-LDL-induced HUVECs were improved again. Taken together, NEDD4 attenuated ox-LDL-induced inflammation and endothelial dysfunction by regulating APEX1 expression.

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“…NEDD4 is a type of ubiquitin-like protein, and its covalent bonding to a substrate is known as neddylation ( 28 ). An important physiological function of neddylation is to regulate E3 ubiquitin-ligating enzymes and promote the progression of the ubiquitination pathway ( 29 , 30 ). Furthermore, the family of cullin proteins includes the substrates on which NEDD4 primarily acts.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have reported that NEDD4 serves an important role in cancer development ( 29 , 30 ). NEDD4 is highly expressed in patients with breast ( 35 ) and lung cancer ( 36 ), where it was closely associated with clinical pathology ( 35 , 36 ).…”

Section: Introductionmentioning

confidence: 99%

NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development

et al. 2021

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The present study aimed to discuss the effects and relative mechanisms of NEDD4 E3 ubiquitin protein ligase (NEDD4) in cutaneous melanoma (CMM) occurrence and development. Clinical cancer and adjacent normal tissues samples were collected to analyze pathological changes and protein expression of NEDD4. Moreover, small interfering (si)RNA was used to knockdown NEDD4 expression in SK-MEL-2 and Malme-3M cells. Cellular proliferation, apoptosis, invasiveness and migration were examined using colony formation, flow cytometric, Transwell and wound-healing assays, respectively. In addition, the relative mRNA and protein expression levels of NEDD4, notch receptor 1 (Notch1) and PTEN were evaluated via reverse transcription-quantitative (RT-q) PCR and western blotting. It was found that NEDD4 mRNA and protein expression were significantly upregulated (both P<0.01). Following NEDD4-knockdown, colony number was significantly decreased, while the apoptotic rate was significantly increased, the invasive cell number was significantly inhibited and the wound-healing capacity was significantly decreased. Following si-NEDD4 transfection, RT-qPCR and western blotting revealed that NEDD4 and Notch1 mRNA and protein expression levels were significantly downregulated, while those of PTEN were significantly upregulated in the SK-MEL-2 and Malme-3M cell lines. Collectively, the current results suggest that NEDD4-knockdown effectively suppressed CMM biological activity by regulating the Notch1/PTEN pathway in vitro .

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NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4

Cited by 11 publications

References 33 publications

Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer

Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer

NEDD4 attenuates oxidized low‑density lipoprotein‑induced inflammation and dysfunction in vascular endothelial cells via regulating APEX1 expression

NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development

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