DUSP4 promotes the carcinogenesis of CCRCC via negative regulation of autophagic death

2021 ◽  
Author(s):  
Xianyou Zeng ◽  
Changyan Zhu ◽  
Xianxin Zhu
Keyword(s):  
Clear Cell ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Cell Renal Cell Carcinoma ◽  
Total Death ◽  
Autophagic Activity ◽  
Lc3 Puncta ◽  
And Migration ◽  
Oncogenic Gene ◽  
Proliferation And Migration

Abstract DUSP4 is considered as an oncogenic gene. However, the effect of DUSP4 on the carcinogenesis of Clear cell Renal cell carcinoma (CCRCC) is still unclear. In this study, DUSP4 mRNA levels were significantly increased in CCRCC tissues and cell lines. Furthermore, DUSP4 overexpression promotes the proliferation, migration and tumorigenicity of CCRCC cells while DUSP4 silencing showed the opposite effects. Importantly, both of autophagic activity (LC3 conversion rate and LC3 puncta formation) and total death level promoted by DUSP4 silencing were reversed by treatment with 3-MA in CCRCC cells. Moreover, the proliferation and migration of CCRCC cells inhibited by DUSP4 silencing were also recovered by suppression of autophagy with 3-MA. In conclusion, DUSP4 serves as an oncogenic gene in CCRCC carcinogenesis due to its inhibitory effect on autophagic death, indicating the potential value of DUSP4 in the diagnosis and treatment of CCRCC.

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.

LncRNA SNHG3 promotes clear cell renal cell carcinoma proliferation and migration by upregulating TOP2A

2019 ◽  
Vol 384 (1) ◽  
pp. 111595 ◽  
Author(s):  
Chong Zhang ◽  
Yan Qu ◽  
Haibing Xiao ◽  
Wen Xiao ◽  
Jing Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Actin-binding protein profilin1 promotes aggressiveness of clear-cell renal cell carcinoma cells

2020 ◽  
Vol 295 (46) ◽  
pp. 15636-15649 ◽  
Author(s):  
Abigail Allen ◽  
David Gau ◽  
Paul Francoeur ◽  
Jordan Sturm ◽  
Yue Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Cell ◽  
Stromal Cells ◽  
Clear Cell ◽  
Actin Binding ◽  
Vascular Endothelial ◽  
Cell Renal Cell Carcinoma ◽  
And Migration ◽  
Proliferation And Migration

Clear-cell renal cell carcinoma (ccRCC), the most common subtype of renal cancer, has a poor clinical outcome. A hallmark of ccRCC is genetic loss-of-function of VHL (von Hippel–Lindau) that leads to a highly vascularized tumor microenvironment. Although many ccRCC patients initially respond to antiangiogenic therapies, virtually all develop progressive, drug-refractory disease. Given the role of dysregulated expressions of cytoskeletal and cytoskeleton-regulatory proteins in tumor progression, we performed analyses of The Cancer Genome Atlas (TCGA) transcriptome data for different classes of actin-binding proteins to demonstrate that increased mRNA expression of profilin1 (Pfn1), Arp3, cofilin1, Ena/VASP, and CapZ, is an indicator of poor prognosis in ccRCC. Focusing further on Pfn1, we performed immunohistochemistry-based classification of Pfn1 staining in tissue microarrays, which indicated Pfn1 positivity in both tumor and stromal cells; however, the vast majority of ccRCC tumors tend to be Pfn1-positive selectively in stromal cells only. This finding is further supported by evidence for dramatic transcriptional up-regulation of Pfn1 in tumor-associated vascular endothelial cells in the clinical specimens of ccRCC. In vitro studies support the importance of Pfn1 in proliferation and migration of RCC cells and in soluble Pfn1's involvement in vascular endothelial cell tumor cell cross-talk. Furthermore, proof-of-concept studies demonstrate that treatment with a novel computationally designed Pfn1–actin interaction inhibitor identified herein reduces proliferation and migration of RCC cells in vitro and RCC tumor growth in vivo. Based on these findings, we propose a potentiating role for Pfn1 in promoting tumor cell aggressiveness in the setting of ccRCC.

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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