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Title: Sirt2 suppresses glioma cell growth through targeting NF-κB–miR-21 axis

Highlights: •Sirt2 expression is down-regulated in human glioma tissues and cell lines. •Sirt2 regresses glioma cell growth and colony formation via inducing apoptosis. •miR-21 is essential for the functions of Sirt2 in glioma cells. •Sirt2 deacetylates p65 to decrease miR-21 expression. -- Abstract: Sirtuins are NAD{sup +}-dependent deacetylases that regulate numerous cellular processes including aging, DNA repair, cell cycle, metabolism, and survival under stress conditions. The roles of sirtuin family members are widely studied in carcinogenesis. However, their roles in glioma remain unclear. Here we report that Sir2 was under expressed in human glioma tissues and cell lines. We found that Sirt2 overexpression decreased cell proliferation and colony formation capacity. In addition, Sirt2 overexpression induced cellular apoptosis via up-regulating cleaved caspase 3 and Bax, and down-regulating anti-apoptotic protein Bcl-2. Sirt2 knockdown obtained opposing results. We showed that Sirt2 overexpression inhibited miR-21 expression, and Sirt2 was not sufficient to reduce cell proliferation and colony formation as well as to induce apoptosis when miR-21 was knocked down in glioma cells. Mechanically, we demonstrated that Sirt2 deacetylated p65 at K310 and blocked p65 binding to the promoter region of miR-21, thus regressing the transcription of miR-21. In summary, Sirt2 is critical in humanmore » glioma via NF-κB–miR-21 pathway and Sirt2 activator may serve as candidate drug for glioma therapy.« less
Authors:
;  [1] ; ;  [2] ;  [3] ;  [1]
  1. Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai (China)
  2. Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai (China)
  3. Department of Rheumatology, Changzheng Hospital, Second Military Medical University, Shanghai (China)
Publication Date:
OSTI Identifier:
22242198
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 441; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; CARCINOGENESIS; CELL CYCLE; CELL PROLIFERATION; COLONY FORMATION; DNA REPAIR; DRUGS; GLIOMAS; METABOLISM; NAD; PROMOTERS; PROTEINS; TRANSCRIPTION