| Autor: |
Dingwen Gui, Zhufeng Dong, Wei Peng, Weidong Jiang, Geng Huang, Gang Liu, Zhihua Ye, Yang Wang, Zuwei Xu, Jinlun Fu, Shuai Luo, Yunfei Zhao |
| Rok vydání: |
2020 |
| Popis: |
Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignant diseases in the urinary system with more than 140,000 related deaths annually. The lack of effective tumor biomarkers and understanding of the molecular mechanisms of this disease make the difficulty in the diagnosis and treatment. Ubiquitination-deubiquitination homeostasis is an important factor in ccRCC progression, ubiquitin specific peptidase 53 (USP53) belongs to the family of deubiquitinating enzymes, but its functions are rarely reported. Methods Databases obtained from GEO and TCGA were analyzed to reveal the role of USP53 in ccRCC. CCK-8/BrdU and EDU assays were used to detect the proliferation of ccRCC after USP53 overexpression or knockdown. Tumor xenograft experiment was used to verify the effect of clone formation of ccRCC after USP53 knockdown. Transwell assays were used to detect the metastasis of ccRCC after USP53 overexpression or knockdown. RNA sequencing and western blot analysis were employed to detect the change of genes after USP53 overexpression and knockdown. Results USP53 expression was down-regulated in ccRCC tissues and USP53 expression was significantly negative correlated with the tumor progression and clinical prognosis. The ability of growth and metastasis of ccRCC was inhibited after USP53 overexpression. And USP53 knockdown promoted ccRCC growth and metastasis. Moreover USP53 knockdown promoted the ability of clone formation of ccRCC in vivo . NF-κB signaling pathway significantly enriched and down regulated in USP53 overexpressed cells. And genes in the NF-κB pathway (such as IL1B, CXCL1-3, RELA, RELB, etc.) were obviously down regulated in USP53 overexpressed cells. USP53 overexpression decreased the phosphorylation of IKKβ and P65 in both Caki-1 and 786-O cells. And the expression of IκBα was increased. Phosphorylation of IKKβ and P65 was increased in both Caki-1 and 786-O cells after USP53 knockdown. Conclusion In summary, our data showed that USP53 inhibit ccRCC proliferation and metastasis through NF-κB pathway inactivation. The overexpression of USP53 is accompanied by changes in many inflammatory genes in the NF pathway. These findings may help better understand the pathogenesis of ccRCC and introduce new potential therapeutic targets for kidney cancer patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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