Novel genetic variants in <i>KIF16B</i> and <i>NEDD4L</i> in the endosome‐related genes are associated with nonsmall cell lung cancer survival

Yang, Sen; Tang, Dongfang; Zhao, Yu; Liu, Hongliang; Luo, Sheng; Stinchcombe, Thomas E.; Glass, Carolyn; Su, Li; Shen, Sipeng; Christiani, David C.; Wang, Qiming; Wei, Qingyi

doi:10.1002/ijc.32739

Cited by 10 publications

(14 citation statements)

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“…However, the detailed role of NEDD4-like proteins in LUAD pathogenesis is still unclear. Here, our integrated bioinformatics analysis demonstrated a prognostic value of NEDD4L in LUAD, which was consistent with the results observed by Yang et al in lung cancer [33]. GSEA results indicated that genes regulated by NEDD4L were enriched in the mTORC1 pathway (Figure 3A&3B).…”

Section: Discussionsupporting

confidence: 91%

Downregulation of NEDD4L by EGFR Signaling Promotes the Development of Lung Adenocarcinoma

Song

et al. 2021

Preprint

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Cumulative evidence indicates that the abnormal regulation of the NEDD4 family of E3-ubiquitin ligases participates in the tumorigenesis and development of cancer. However, their role in lung adenocarcinoma (LUAD) remains unclear. This study comprehensively analyzed the NEDD4 family in LUAD data sets from public databases and found only NEDD4L was associated with the overall survival of LUAD patients. Gene set enrichment analysis (GSEA) indicated that NEDD4L might be involved in the regulation of mTORC1 pathway. Both cytological and clinical assays showed that NEDD4L inhibited the activity of the mTOR signaling pathway. In vivo and in vitro experiments showed that NEDD4L could significantly inhibit the proliferation of LUAD cells. In addition, this study also found that the expression of NEDD4L was regulated by EGFR signaling. These findings firstly revealed that NEDD4L mediates an interplay between EGFR and mTOR pathways in LUAD, and suggest that NEDD4L held great potential as a novel biomarker and therapeutic target for LUAD.

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Section: Discussionsupporting

confidence: 91%

Downregulation of NEDD4L by EGFR Signaling Promotes the Development of Lung Adenocarcinoma

Song

et al. 2021

Preprint

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“…It suggested that NEDD4L acted as an anti-oncogene in BRCA, consistent with Lee's study [32]. Previous studies have shown that NEDD4L plays an anti-cancer role in carcinomas, such as glioma, lung cancer, and colorectal cancer [23,33,34]. Furthermore, we performed GO and KEGG analysis and found that the differential genes between the two subgroups enriched in the TGF-β pathway, which plays a vital role in the EMT and metastasis of BRCA [4].…”

Section: Discussionsupporting

confidence: 87%

E3 Ubiquitin Ligase NEDD4L Negatively Regulates Breast Cancer Metastasis By Downregulating SNAI2

Zuo¹,

Li²,

Li³

et al. 2021

Preprint

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Background Accumulating evidence demonstrated that the abnormal expression of E3-ubiquitin ligase NEDD4L plays an important role in the biological process of carcinomas. However, its role in breast cancer (BRCA) remains elusive. Methods The expression of NEDD4L was analyzed using BRCA datasets from public database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Both transwell assay and pulmonary metastasis model of BRCA were used to detect metastatic ability of cells. Western blotting, immunohistochemistry and immunofluorescence assay were used to detect the protein expression of target genes. The riskScore and nomogram were used to evaluate the prognosis of patients. Results NEDD4L was significantly downregulated in cancer tissues and positively correlated with the overall survival of patients. Knocking down NEDD4L could enhance the migration and metastasis ability of BRCA cells. SP1 promotes NEDD4L expression, resulting in SNAI2 downregulation in BRCA. A NEDD4L related to the prognostic model developed by LASSO Cox regression could be an independent predictive factor for BRCA. A nomogram combining riskScore and clinical indicators was established to evaluate the prognosis of BRCA quantitatively. Conclusions This study first reveals the role of the SP1/NEDD4L/SNAI2 axis in BRCA and establishes a reliable prognostic model, which provides a novel target and basis for clinical treatment and prognosis evaluation of breast cancer.

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“…Moreover, NEDD4L expression was appreciably link to the clinical outcome of CN-AML. Although it is the first report regarding the prognostic significance of NEDD4L expression in AML, several studies have shown the great correlations of NEDD4L expression with clinical outcome in solid tumors [ 9 – 16 ]. Reduced expression of NEDD4L correlated with adverse prognosis in non-small cell lung cancer, gastric cancer, hepatocellular carcinoma, ovarian cancer, and malignant glioma [ 9 – 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…NEDD4L is originally discovered in identifying for downregulated genes during the development of the central nervous system [ 7 , 8 ]. Recently, there is mounting evidence that showed the association of NEDD4L expression with prognosis in diverse human cancers [ 9 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia

et al. 2021

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Background There is mounting evidence that demonstrated the association of aberrant NEDD4L expression with diverse human cancers. However, the expression pattern and clinical implication of NEDD4L in acute myeloid leukemia (AML) remains poorly defined. Methods We systemically determined NEDD4L expression with its clinical significance in AML by both public data and our research cohort. Moreover, biological functions of NEDD4L in leukemogenesis were further tested by in vitro experiments. Results By the public data, we identified that low NEDD4L expression was correlated with AML among diverse human cancers. Expression of NEDD4L was remarkably decreased in AML compared with controls, and was confirmed by our research cohort. Clinically, low expression of NEDD4L was correlated with greatly lower age, higher white blood cells, and higher bone marrow/peripheral blood blasts. Moreover, NEDD4L underexpression was positively correlated with normal karyotype, FLT3 and NPM1 mutations, but negatively associated with complex karyotype and TP53 mutations. Importantly, the association between NEDD4L expression and survival was also discovered in cytogenetically normal AML patients. Finally, a number of 1024 RNAs and 91 microRNAs were identified to be linked to NEDD4L expression in AML. Among the negatively correlated microRNAs, miR-10a was also discovered as a microRNA that may directly target NEDD4L. Further functional studies revealed that NEDD4L exhibited anti-proliferative and pro-apoptotic effects in leukemic cell line K562. Conclusions Our findings indicated that NEDD4L underexpression, as a frequent event in AML, was associated with genetic abnormalities and prognosis in AML. Moreover, NEDD4L expression may be involved in leukemogenesis with potential therapeutic target value.

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Novel genetic variants in KIF16B and NEDD4L in the endosome‐related genes are associated with nonsmall cell lung cancer survival

Cited by 10 publications

References 50 publications

Downregulation of NEDD4L by EGFR Signaling Promotes the Development of Lung Adenocarcinoma

Downregulation of NEDD4L by EGFR Signaling Promotes the Development of Lung Adenocarcinoma

E3 Ubiquitin Ligase NEDD4L Negatively Regulates Breast Cancer Metastasis By Downregulating SNAI2

Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia

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