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TitleSirtuins’ deregulation in bladder cancer: SIRT7 is implicated in tumor progression through epithelial to mesenchymal transition promotion
Author(s)Monteiro-Reis, Sara
Lameirinhas, Ana
Miranda-Gonçalves, Vera
Felizardo, Diana
Dias, Paula C.
Oliveira, Jorge
Graça, Inês
Gonçalves, Celine Saraiva
Costa, Bruno Marques
Henrique, Rui
Jerónimo, Carmen
Keywordsbladder cancer
Issue date25-Apr-2020
PublisherMultidisciplinary Digital Publishing Institute
CitationMonteiro-Reis, S.; Lameirinhas, A.; Miranda-Gonçalves, V.; Felizardo, D.; Dias, P.C.; Oliveira, J.; Graça, I.; Gonçalves, C.S.; Costa, B.M.; Henrique, R.; Jerónimo, C. Sirtuins’ Deregulation in Bladder Cancer: SIRT7 Is Implicated in Tumor Progression through Epithelial to Mesenchymal Transition Promotion. Cancers 2020, 12, 1066.
Abstract(s)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<sup>me3</sup> 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.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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