SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3

Chen, Yanbing; Zhu, Ying; Sheng, Yanling; Xiao, Jianghong; Yu, Xiao; Cheng, Na; Chai, Yong; Wu, Xiaoping; Zhang, Shouhua; Xiang, Tianxin

doi:10.1016/j.yexcr.2019.06.011

Cited by 26 publications

(19 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This impairs SIRT1 deacetylase activity, resulting in increased NRF2 nuclear translocation and consequent transcriptional activity [72]. This is in line with several studies underlying the involvement of class III histone deacetylases in multiple processes of cancer initiation and progression and associating SIRT1 downregulation in RCCs with a poor prognosis [73][74][75].…”

Section: Mutations In Genes That Directly or Indirectly Affect Keap1-supporting

confidence: 73%

Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma

Clerici

Boletta

2020

Cancers

View full text Add to dashboard Cite

NRF2 is a transcription factor that coordinates the antioxidant response in many different tissues, ensuring cytoprotection from endogenous and exogenous stress stimuli. In the kidney, its function is essential in appropriate cellular response to oxidative stress, however its aberrant activation supports progression, metastasis, and resistance to therapies in renal cell carcinoma, similarly to what happens in other nonrenal cancers. While at the moment direct inhibitors of NRF2 are not available, understanding the molecular mechanisms that regulate its hyperactivation in specific tumor types is crucial as it may open new therapeutic perspectives. Here, we focus our attention on renal cell carcinoma, describing how NRF2 hyperactivation can contribute to tumor progression and chemoresistance. Furthermore, we highlight the mechanism whereby the many pathways that are generally altered in these tumors converge to dysregulation of the KEAP1-NRF2 axis.

show abstract

Section: Mutations In Genes That Directly or Indirectly Affect Keap1-supporting

confidence: 73%

Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma

Clerici

Boletta

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…However, it was also reported that SIRT1 expression was significantly lower in RCC than in normal tissues and high expression of SIRT1 was correlated with a better prognosis for RCC patients (8). SIRT1 overexpression inhibited RCC cell line proliferation by repressing FGB expression (9). In our study, the mRNA expression of SIRT1 was up-regulated in KIRC than in normal tissues.…”

Section: Discussionsupporting

confidence: 47%

“…Several studies have been conducted to explore the clinical significance of sirtuins in RCC, however, the results are inconsistent. The protein expression of SIRT1, SIRT3, and SIRT6 have been reported to be significantly lower in human RCC tissues compared with that in adjacent normal tissues, and high protein expression levels of SIRT1 and SIRT3 were found to be significantly associated with better survival in RCC patients (8,9). However, SIRT1 was also reported to be up-regulated in RCC and the expression of SIRT1 was significantly associated with poor prognosis in RCC patients (10).…”

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of Sirtuins and Their Prognostic Significance in Clear Cell Renal Cell Carcinoma

Tan

Peng

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Sirtuins, class III histone deacetylases, are involved in multiple biological processes in cancer initiation and progression. However, the diverse expression patterns and prognostic values of sirtuins in cancers have yet to be elucidated. In this study, we first evaluated the expression and prognostic values of sirtuins in multiple cancer cohorts using publicly available TCGA pan-cancer datasets. Pan-cancer survival analysis indicated that 6 out of 7 sirtuin family members were significant associated with prognosis of clear cell renal cell carcinoma (KIRC) patients. SIRT1, SIRT3, SIRT4, and SIRT5 were associated with favorable prognosis of KIRC patients, while SIRT6 and SIRT7 were associated with unfavorable prognosis. The expression levels of SIRT4 and SIRT5 in KIRC tissues were lower than that in normal tissues, while SIRT6 and SIRT7 were higher in KIRC tissues. The expression levels of SIRT1, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly correlated with tumor stage and histological grade. DNA methylation may contribute to the dysregulation of sirtuins. Finally, GSEA was conducted to predict the potential functions of sirtuins in KIRC. Our results may provide novel insights for the development of sirtuins-based cancer therapy in KIRC.

show abstract

“…Previous studies (38,39) have emphasized SIRT1 as a potential tumor suppressor protein to inhibit RCC tumorigenesis, but the role of SIRT1/AMPK signaling in RCC progression is yet to be clarified (40). The present study used western blotting and immunohistochemistry to detect the expression levels of SIRT1 in clinical samples, revealing lower SIRT1 expression (41)(42)(43).…”

Section: Discussionmentioning

confidence: 79%

Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells

Wang

Tuo

et al. 2021

Oncol Rep

View full text Add to dashboard Cite

Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates several bioactive substances, and the present study aimed to identify the role of SIRT1/AMP-activated protein kinase (AMPK) signaling in RCC progression. SIRT1 expression was detected in 100 patients with RCC using tissue microarray immunohistochemistry. SIRT1-knockdown and overexpression were performed via RNA interference and plasmid transfection. Inhibition of AMPK was used for the phenotypic rescue assays to verify whether AMPK was a downstream target of SIRT1. Reverse transcription-quantitative PCR was performed to verify transfection efficiency. Transwell, MTT and flow cytometry apoptosis assays were performed to evaluate the migration, invasion, proliferation and early apoptosis level of RCC cells. SIRT1 and AMPK protein expression in human RCC tissues and cell lines (786-O and ACHN) was detected using western blotting and immunofluorescence staining. The current results, combined with data from The Cancer Genome Atlas database, revealed that SIRT1 expression in RCC tissues was downregulated compared with in adjacent normal tissues. Additionally, high SIRT1 expression was associated with an improved prognosis in patients with RCC. Overexpression of SIRT1 inhibited the proliferation, migration and invasion of RCC cell lines and induced apoptosis, while inhibition of SIRT1 expression had the opposite effects. Further experiments indicated that SIRT1 may serve an anticancer role by upregulating the expression levels of downstream AMPK, thus revealing a potential therapeutic target for RCC.

show abstract

SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3

Cited by 26 publications

References 44 publications

Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma

Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma

Integrative Analysis of Sirtuins and Their Prognostic Significance in Clear Cell Renal Cell Carcinoma

Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells

Contact Info

Product

Resources

About