CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats
| Autor: | Adaugo C Isichei, Afnan Al-Muhnna, Amany I. Alqosaibi, Hamdy Rizk, Abdelbary Prince, Shaimaa Abdel-Ghany, Khalid Farid, Fatma Al-Mulhim, Hussein Sabit |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
CDH1
Angiogenesis QH301-705.5 Mammary gland Cancer Biology Adenocarcinoma medicine.disease medicine.disease_cause Applied Microbiology and Biotechnology Metastasis Activation of CDH1 Breast cancer medicine.anatomical_structure Cancer cell Breast Cancer Cancer research medicine Biology (General) Carcinogenesis CRISPR/Cas9 TP248.13-248.65 CDK11 Biotechnology |
| Zdroj: | Electronic Journal of Biotechnology, Vol 53, Iss, Pp 54-60 (2021) |
| ISSN: | 0717-3458 |
| Popis: | Background: Cancer 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. Results: qPCR 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. Conclusions: Although 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. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tabla normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0cm; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} |
| Databáze: | OpenAIRE |
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