期刊
CANCERS
卷 12, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cancers12051066
关键词
bladder cancer; SIRT7; EMT
类别
资金
- Research Center of the Portuguese Oncology Institute of Porto [CI-IPOP-FBGEBC-27, PI 74-CI-IPOP-19-2016]
- Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/112673/2015, SFRH/BD/92786/2013, IF/00601/2012]
- Fundo Europeu de Desenvolvimento Regional (FEDER) [IPO/ESTIMANORTE01-0145-FEDER-000027, COMPETE/FEDER/FCT_CI-IPOP-BPD/UID/DTP/00776/2013]
- Fundação para a Ciência e a Tecnologia [UID/DTP/00776/2013, SFRH/BD/112673/2015, SFRH/BD/92786/2013] Funding Source: FCT
Sirtuins are emerging players in cancer biology and other age-related disorders, and their putative role in bladder cancer (BlCa) remains elusive. Further understanding of disease biology may allow for generation of more effective pathway-based biomarkers and targeted therapies. Herein, we aimed to illuminate the role of sirtuins' family in BlCa and evaluate their potential as disease biomarkers and therapeutic targets. SIRT1-7 transcripts and protein levels were evaluated in a series of primary BlCa and normal bladder mucosa tissues. SIRT7 knockdown was performed through lentiviral transduction in MGHU3, 5637 and J82 cells and its functional role was assessed. SIRT1, 2, 4 and 5 expression levels were significantly lower in BlCa, whereas SIRT6 and 7 were overexpressed, and these results were corroborated by TCGA cohort analysis. SIRT7 transcript levels were significantly decreased in muscle-invasive vs. papillary BlCa. In vitro studies showed that SIRT7 downregulation promoted cells migration and invasion. Accordingly, increased EMT markers expression and decreased E-Cadherin (CDH1) was observed in those BlCa cells. Moreover, increased EZH2 expression and H3K27(me3) deposition in E-Cadherin promoter was found in sh-SIRT7 cells. We demonstrated that sirtuins are globally deregulated in BlCa, and specifically SIRT7 downregulation is implicated in EMT, fostering BlCa invasiveness through EZH2-CDH1 axis.
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