Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro

Turkish journal of biology

article

TAHA BARTU HAYAL¹  AYŞEGÜL DOĞAN¹  HATİCE BURCU ŞİŞLݹ  BİNNUR KIRATLI¹  FİKRETTİN ŞAHİN¹ 

[1] Yeditepe University, Department of Genetics and Bioengineering, Faculty of Engineering

关键词: Ubiquitination;    breast cancer;    USP7;    p5091;    gene editing;   

DOI  :  10.3906/biy-1912-83

学科分类：生物科学（综合）

来源: Scientific and Technical Research Council of Turkey - TUBITAK

【 摘 要 】

Because breast cancer is complicated at the pathological, histological, clinical, and molecular levels, identification of new genetic targets against carcinogenic pathways is required to generate clinically relevant treatment options. In the current study, ubiquitinspecific protease 7 (USP7), which regulates various cellular pathways including Mdm2, p53, and NFκB, was selected as a potential gene editing strategy for breast cancer in vitro. Anticancer activity of USP7 gene suppression has been evaluated through cell proliferation, gene expression, cell cycle, sphere dissemination, and cell migration analysis. Here, siRNA and shRNA strategies and an allosteric small-molecule inhibitor of USP7 were used to define potential anticancer activity against MCF7 and T47D human breast cancer cell lines. Both blockage of deubiquitination by p5091 and knockdown of USP7 reduced cell proliferation, cell migration, colony formation, and sphere dissemination for both MCF7 and T47D breast cancer cell lines. Restriction of USP7 activity strongly enhanced apoptotic gene expression and reduced metastatic ability of breast cancer cell lines. This study describes one potential molecular target for the suppression of breast cancer proliferation and metastasis. Identification of USP7 as a promising gene editing candidate might open up the possibility of new molecular drug research in targeting the ubiquitination pathway in cancer.

【 授权许可】

Unknown