scholarly journals Ubiquitin-specific protease 44 inhibits cell proliferation and migration via inhibition of JNK pathway in clear cell renal cell cancer

2019 ◽  
Author(s):  
Jiangqiao Zhou ◽  
Tianyu Wang ◽  
Tao Qiu ◽  
Zhongbao Chen ◽  
Xiaoxiong Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Cell Renal Cell Carcinoma ◽  
Jnk Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Ccrcc Cell ◽  
Proliferation And Migration

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. USP44 has been reported to be involved in various cancers. This study aimed to investigate the function role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from TCGA data portal and GSO database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. The function of USP44 in cell proliferation and migration was assessed by cellular and molecular analysis. Results: USP44 was lowly expressed in the ccRCC cancer tissues compared to the normal tissue. Further, USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression significantly inhibited tumor cell proliferation and migration of 786-O cell as well as Caki-1 cell. In addition, USP44 overexpression also prohibited cell proliferation by up-regulating P21, down-regulating Cyclin D1 expression, and inhibited cell migration by up-regulating MMP2 and MMP9 expression. In contrast, USP44 knockdown enhances ccRCC cell proliferation and migration. Furthermore, the USP44 function in inhibiting ccRCC cell proliferation and migration is associated with the phosphorylation level of JNK. Conclusion: In summary, this study showed that USP44 may be a marker in predicting the ccRCC progression and USP44 inhibits ccRCC cell proliferation and migration dependent on the JNK pathway.

scholarly journals Ubiquitin-specific protease 44 inhibits cell proliferation and migration via inhibition of JNK pathway in clear cell renal cell cancer

2019 ◽  
Author(s):  
Jiangqiao Zhou ◽  
Tianyu Wang ◽  
Tao Qiu ◽  
Zhongbao Chen ◽  
Xiaoxiong Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Cell Renal Cell Carcinoma ◽  
Jnk Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Ccrcc Cell ◽  
Proliferation And Migration

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. USP44 has been reported to be involved in various cancers. This study aimed to investigate the function role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from TCGA data portal and GSO database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. The function of USP44 in cell proliferation and migration was assessed by cellular and molecular analysis. Results: USP44 was lowly expressed in the ccRCC cancer tissues compared to the normal tissue. Further, USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression significantly inhibited tumor cell proliferation and migration of 786-O cell as well as Caki-1 cell. In addition, USP44 overexpression also prohibited cell proliferation by up-regulating P21, down-regulating Cyclin D1 expression, and inhibited cell migration by up-regulating MMP2 and MMP9 expression. In contrast, USP44 knockdown enhances ccRCC cell proliferation and migration. Furthermore, the USP44 function in inhibiting ccRCC cell proliferation and migration is associated with the phosphorylation level of JNK. Conclusion: In summary, this study showed that USP44 may be a marker in predicting the ccRCC progression and USP44 inhibits ccRCC cell proliferation and migration dependent on the JNK pathway.

scholarly journals BATF Inhibits Cell Proliferation and Migration via PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Ming Li ◽  
Jun Jin ◽  
Zhihui Yang ◽  
Xiaoli Chen ◽  
Yongzhong Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Mtor Signaling Pathway ◽  
Cell Renal Cell Carcinoma ◽  
And Migration ◽  
Ccrcc Cell ◽  
Proliferation And Migration

Abstract Background Previous studies reported that BATF played an important role in the progression of various cancers, but no report had been found on clear cell renal cell carcinoma(ccRCC). So we investigated the effects of BATF on the progression of ccRCC. Methods In this study, using TCGA-KIRC database from the Cancer Genome Atlas to analyze the differential genes of BATF in ccRCC ; using immunohistochemistry to detect BATF expression in 75 ccRCC tumorous and 28 nontumorous tissues, and investigate its relationship with clinicopathological parameters. Moreover, we constructed the cell lines of BATF overexpression and knockout in Caki-1and 786-0 ccRCC cell lines and confirmed by western blot. CCK8 assay was used to evaluated the cell viability and using EdU staining to detect cell proliferation; using Transwell experiment to investigate the affection of BATF in ccRCC cell migration. Westernblot was used to detect the phosphorylation of PI3K/AKT/mTOR. Results These results revealed that BATF expression in ccRCC tumorous was significantly higher compared with that in adjacent nontumorous tissues and was significantly correlated with T stage, Fuhrman grade, Tumor necrosis and status. In addiditon, BATF overexpression significantly inhibited the viability, proliferation and migration of the two cell lines. More importantly, using westernblot showed that silencing BATF significantly increased the level of phosphorylated AKT, PI3K and mTOR, while BATF overexpression decreased phosphorylation that involved in the PI3K/Akt/mTOR signaling pathway. Conclusions Our findings demonstrate that BATF plays an important role in the progression of ccRCC and it may act as an tumor supressor gene to inhibit the progression of ccRCC through regulating the PI3K/Akt/mTOR signaling pathway.

scholarly journals Neuropilin 1 and Neuropilin 2 Gene Invalidation or Pharmacological Inhibition Reveals Their Relevance for the Treatment of Metastatic Renal Cell Carcinoma

2020 ◽  
Author(s):  
Aurore Dumond ◽  
Etienne Brachet ◽  
Jérôme Durivault ◽  
Valérie Vial ◽  
Anna K. Puszko ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Dependent Manner ◽  
Cell Renal Cell Carcinoma ◽  
Immunodeficient Mice ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Despite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent ®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analysed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.Methods: We correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for the NRP1 and NRP2 genes by a CRISPR/Cas9 method. Their proliferation and migration were evaluated by XTT or impedance tests and by wound closure. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were performed in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking on both NRPs was performed.Results: Invalidation of the NRP1 and NRP2 genes inhibited cell proliferation and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell proliferation and migration more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice in a reverse dose dependent manner. Such inhibition was associated with a decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that NRP2, more than NRP1 correlates with tumor aggressiveness only in metastatic patients.Conclusion: Our study strongly suggests that inhibiting NRP is a good therapeutic strategy for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.

scholarly journals Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

Oncotarget ◽  
2014 ◽  
Vol 5 (14) ◽  
pp. 5320-5334 ◽  
Author(s):  
Christina A. von Roemeling ◽  
Laura A. Marlow ◽  
Derek C. Radisky ◽  
Austin Rohl ◽  
Hege E. Larsen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Clear Cell ◽  
Tumor Cell Proliferation ◽  
Cell Renal Cell Carcinoma ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Carcinoma Tumor ◽  
Proliferation And Migration

scholarly journals Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Jiangqiao Zhou ◽  
Tianyu Wang ◽  
Tao Qiu ◽  
Zhongbao Chen ◽  
Xiaoxiong Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Jnk Pathway ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells).Results: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by upregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK).Conclusion: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.

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