NEDD4L Regulates the Proliferation and Metastasis of Non-small-cell Lung Cancer by Mediating CPNE1 Ubiquitination

2021 ◽  
Author(s):  
Ruochen Zhang ◽  
Yuanyuan Zeng ◽  
Weijie Zhang ◽  
Yue Li ◽  
Jieqi Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Post Translational Modification ◽  
Small Cell Lung ◽  
Direct Role ◽  
Ubiquitin Proteasome ◽  
Proliferation And Metastasis ◽  
Ubiquitin Molecule

Abstract High expression of CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), suggesting that CPNE1 may be an effective target for the treatment of NSCLC. No direct role of post-translational modification of CPNE1 in NSCLC has been reported. This study confirms that CPNE1 is degraded by two pathways: the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. CPNE1 binds with the ubiquitin molecule via its K157 residue. Moreover, we determine that the ubiquitin ligase NEDD4L can mediate the ubiquitination of CPNE1 and promote its degradation. In addition, we find that NEDD4L knockout promotes the proliferation and metastasis of NSCLC cells by regulating CPNE1. This study aims to further investigate the mechanism of CPNE1 ubiquitination in the occurrence and development of NSCLC and provide a new potential target for NSCLC treatment.

scholarly journals The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ruochen Zhang ◽  
Weijie Zhang ◽  
Yuanyuan Zeng ◽  
Yue Li ◽  
Jieqi Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Post Translational Modification ◽  
Small Cell Lung ◽  
Direct Role ◽  
Micro Rnas ◽  
Ubiquitin Proteasome

AbstractOur previous studies revealed that oncogene CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), and it could be regulated by micro RNAs. But no direct role of post-translational modification of CPNE1 in NSCLC has been reported. This study confirms that CPNE1 is degraded by two pathways: the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. CPNE1 binds with the ubiquitin molecule via its K157 residue. Moreover, we determined that the ubiquitin ligase NEDD4L can mediate the ubiquitination of CPNE1 and promote its degradation. In addition, we find that NEDD4L knockdown promotes the proliferation and metastasis of NSCLC cells by regulating CPNE1 in vitro and vivo. This study aims to further investigate the mechanism of CPNE1 ubiquitination in the occurrence and development of NSCLC and provide a new potential target for NSCLC treatment.

The Rho-kinase inhibitor inhibits proliferation and metastasis of small cell lung cancer

2012 ◽  
Vol 66 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Xueying Yang ◽  
Jing Di ◽  
Yang Zhang ◽  
Suning Zhang ◽  
Jibin Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Small Cell ◽  
Small Cell Lung ◽  
Rho Kinase Inhibitor ◽  
Proliferation And Metastasis

MiR-760 suppresses non-small cell lung cancer proliferation and metastasis by targeting ROS1

2018 ◽  
Vol 25 (19) ◽  
pp. 18385-18391 ◽  
Author(s):  
Chunhua Yan ◽  
Wei Zhang ◽  
Xiaodong Shi ◽  
Jiaolin Zheng ◽  
Xiaoming Jin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Proliferation ◽  
Proliferation And Metastasis

scholarly journals Long noncoding RNA MIAT promotes non-small cell lung cancer proliferation and metastasis through MMP9 activation

Oncotarget ◽  
2017 ◽  
Vol 8 (58) ◽  
pp. 98148-98162 ◽  
Author(s):  
I-Lu Lai ◽  
Chin-An Yang ◽  
Pei-Chin Lin ◽  
Wen-Ling Chan ◽  
Ya-Ting Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Proliferation ◽  
Proliferation And Metastasis ◽  
Mmp9 Activation

scholarly journals Exosomal miR-3180-3p Inhibits Proliferation and Metastasis of Non-Small Cell Lung Cancer by Downregulating FOXP4

2020 ◽  
Author(s):  
Tengfei Chen ◽  
Yali Liu ◽  
Chang Li ◽  
Chun Xu ◽  
Cheng Ding ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Gene Assay ◽  
Proliferation And Metastasis

Abstract Background: Non-small cell lung cancer (NSCLC) is the most malignant cancers worldwide, but the pathogenesis is not completely known. In this study, we explored the function and mechanism of exosomes transferring miR-3180-3p in NSCLC progression.Method: The expression of miR-3180-3p of NSCLC tissues and para-carcinoma tissues was from the GEO database (GEO: GSE53882). The exosomes derived from A549 cells were identified. The proliferation, migration and invasion were measured after treatment with exosomal miR-3180-3p or transfected by miR-3180-3p mimics. The relationship between miR-3180-3p and forkhead box P4 (FOXP4) was predicted by bioinformatics tool and measured dual-luciferase reporter gene assay and western blotting. At last, mouse xenograft model of NSCLC cells was established to verify the function of exosomal miR-3180-3p in vivo.Results: We found that miR-3180-3p decreased in both NSCLC cell lines and patient tissues. Overexpression of miR-3180-3p or treatment with exosomal miR-3180-3p significantly repressed the cell proliferation and metastasis in NSCLC cell lines. Subsequently, we found miR-3180-3p performed function by downregulating FOXP4 protein expression. Furthermore, the volume and weight of nude mice tumor which expressed exosomal miR-3180-3p was significantly reduced. Conclusion: Exosomal miR-3180-3p suppresses NSCLC progression by downregulating FOXP4 expression.

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