Journal
EXPERIMENTAL CELL RESEARCH
Volume 382, Issue 2-3, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.06.011
Keywords
Renal cell carcinoma; SIRT1,FGB,STAT3,ubiquitin-proteasome
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Funding
- National Natural Science Foundation of China [81760115]
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Renal cell carcinoma (RCC) is one of the common lethal urologic tumors. Recent studies revealed that SIRT1 might function as a tumor suppressor during the progression of RCC. In addition, studies showed that FGB expression was abnormally upregulated in RCC and related to the progress of RCC. This study aimed to define the function of SIRT1 and underlying mechanism in the RCC progression. The expression of SIRT1 and FGB in RCC specimens and cells were detected by immunoblotting and immunostaining. Luciferase reporter assay was performed to confirm FGB as the target gene of STAT3. Other methods including stable transfection, co-immunoprecipitation, Western blot, and in vitro and in vivo proliferation assays were also performed. Our results showed that SIRT1 expression was downregulated in RCC tissues compared to adjacent normal tissues and relatively high expression of SIRT1 conferred a better prognosis for patients. Next, we showed that SIRT1 overexpression inhibited RCC tumorigenesis both in vitro and in vivo. In addition, FGB expression was upregulated in RCC tissues and overexpressing SIRT1 reduced FGB expression levels. Furthermore, inhibition of RCC proliferation by SIRT1 overexpression was rescued by FGB overexpression, indicating that SIRT1 inhibited RCC proliferation by repressing FGB expression. Mechanistically, we confirmed that FGB was the target gene of STAT3, and SIRT1 repressed the expression of FGB by deacetylation of STAT3, leading to STAT3 destabilization and degradation. SIRT1 inhibited RCC tumorigenesis by downregulating FGB expression, and this novel SIRT1STAT3-FGB axis provided a potential target for RCC therapy.
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