CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats |
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| Institution: | 1. Breast Imaging Division, KFHU, Imam Abdulrahman Bin Faisal University, Saudi Arabia;2. Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia;3. Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza, Egypt;4. Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt;5. Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt;6. Department of Basic Sciences- Biology Division, Deanship of Preparatory Year, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia;7. Department of Genetics, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia |
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| Abstract: | BackgroundCancer is a life-threatening disease that affects approximately 18 million individuals worldwide. Breast cancer is the most common female neoplasm globally with more than 276,480 new cases of invasive breast cancer expected to be diagnosed in women in the U.S. alone in 2020. Genetic and epigenetic factors play role in the carcinogenesis and progression of this disease. In this study, MCF-7 adenocarcinoma cells were transfected with CRISPR/Cas9 plasmid to either knock out CDK11 or to activate CDH1. Treated cells were allografted into the mammary glands of female rats (150–190 g, 6–8 weeks) to evaluate the capability of these cells to control cancer progression and metastasis.ResultsqPCR data revealed a significant downregulation of CDK11 and upregulation of CDH1. Cell cycle analysis and apoptosis assays indicated the knockout of CDK11 and simultaneous activation of CDH1 resulted in cell cycle arrest at G2/M phase and accumulation of cells at G2. Meanwhile, the percentage of cells that underwent late apoptosis increased in both genome editing hits. Histopathological sectioning data indicated that untransfected MCF-7 cells were capable of developing tumors in the mammary gland and initiation g angiogenesis. Transfected cells significantly restricted cancer cell infiltration/invasion by minimally localizing tumors and inhibiting angiogenesis.ConclusionsAlthough further investigation is needed, the present data indicate the potentiality of using CRISPR/Cas9-based therapy as a promising approach to treat breast cancer. Impact: these data indicate targeting cancer-related genes via any genome editing tool might represent a novel approach to combat cancer.How to cite: Al-Mulhim F, Alqosaibi AI, Al-Muhnna A, et al. CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats. Electron J Biotechnol 2021;53. https://doi.org/10.1016/j.ejbt.2021.06.002 |
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| Keywords: | Activation of CDH1 Adenocarcinoma Breast Cancer CDH1 CDK11 CRISPR/Cas9 Genome editing technology KO Metastasis suppression Rats Therapy breast cancer |
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