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Published on: June 9, 2023
Ubiquitin-specific protease 7 downregulation suppresses breast cancer in vitro
Taha Bartu Hayal1, Ayşegül DoĞan1, Hatice Burcu ŞİŞlİ1
1Yeditepe University, Department of Genetics and Bioengineering, Faculty of Engineering, İstanbul Turkey.
Abstract:
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, ubiquitin-specific protease 7 (USP7), which regulates various cellular pathways including Mdm2, p53, and NF-κB, 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.
Insights
Targeting ubiquitin-specific protease 7 (USP7) shows promise for breast cancer treatment. Suppressing USP7 reduces cancer cell proliferation and metastasis, offering a new molecular target for drug development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer presents complex challenges across pathological, histological, clinical, and molecular levels.
- Novel genetic targets are crucial for developing effective breast cancer treatments.
- Ubiquitin-specific protease 7 (USP7) regulates key cellular pathways relevant to cancer.
Purpose of the Study:
- To investigate ubiquitin-specific protease 7 (USP7) as a gene editing target for breast cancer.
- To evaluate the anticancer activity of USP7 suppression in vitro.
- To explore USP7's role in breast cancer proliferation and metastasis.
Main Methods:
- Utilized siRNA and shRNA for USP7 gene knockdown.
- Employed an allosteric small-molecule inhibitor (p5091) targeting USP7.
- Assessed effects on MCF7 and T47D human breast cancer cell lines.
- Analyzed cell proliferation, gene expression, cell cycle, sphere dissemination, and cell migration.
Main Results:
- USP7 suppression via siRNA/shRNA and inhibitor p5091 reduced cell proliferation and migration in both cell lines.
- USP7 inhibition decreased colony formation and sphere dissemination.
- Targeting USP7 enhanced apoptotic gene expression.
- Reduced metastatic potential was observed in treated breast cancer cells.
Conclusions:
- USP7 is a potential molecular target for suppressing breast cancer proliferation and metastasis.
- USP7 gene editing strategies show promise for novel breast cancer therapies.
- Targeting the ubiquitination pathway via USP7 could lead to new molecular drug research.
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