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• W4323353642 abstract "Abstract Background USP51 is a deubiquitinase (DUB), which is involved in diverse cellular processes. Accumulating evidence has demonstrated that USP51 contributes to cancer development. However, its impact on non-small-cell lung carcinoma (NSCLC) cell malignancy is largely unknown. Methods In this study, we performed bioinformatics analysis on a TCGA (The Cancer Genome Atlas) dataset to determine the association between USP51 and cell stemness markers in NSCLC patients. RT-qPCR, western blotting, and flow cytometry were performed to examine the effects of USP51 depletion on stemness marker expression. Colony formation and tumor sphere formation assays were used to assess the stemness of the NSCLC cells. Time-course assays directed by cycloheximide and polyubiquitination experiments were carried out to analyze the effects of USP51 on the TWIST1 protein. TWIST1 was overexpressed in USP51 knockdown NSCLC cells to determine whether TWIST1 is required. The effect of USP51 on the in vivo growth of NSCLC cells was tested through subcutaneous injections in mice. Results We found that USP51 expression was positively correlated with several stemness markers in NSCLC patients. USP51 depletion attenuated the stemness marker RNA, protein, and cell surface expression and stemness of NSCLC cells. Ectopic USP51 expression potentiated the TWIST1 protein stability by mitigating its polyubiquitination. In addition, the TWIST1 re-expression in NSCLC cells rescued the stemness-inhibitory effect of USP51 knockdown. Furthermore, in vivo results confirmed the suppressive effect of USP51 depletion on NSCLC cell growth. Conclusions Our results showed that USP51 knockdown alleviated NSCLC cell stemness by deubiquitinating TWIST1." @default.
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• W4323353642 date "2023-03-07" @default.
• W4323353642 modified "2023-10-16" @default.
• W4323353642 title "USP51 promotes non-small-cell lung carcinoma cell stemness by deubiquitinating Twist1" @default.
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• W4323353642 doi "https://doi.org/10.21203/rs.3.rs-2622962/v1" @default.
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