CRISPR-Cas9-Mediated Silencing of CD44 in Human Highly Metastatic Osteosarcoma Cells
| Autor: | Zuyun Yan, Francis J. Hornicek, Yong Liu, Henry J. Mankin, Tang Liu, Edwin Choy, Zhenfeng Duan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Databases Factual Physiology Genetic enhancement Cell Culture Techniques Bone Neoplasms Metastases lcsh:Physiology Metastasis lcsh:Biochemistry 03 medical and health sciences 0302 clinical medicine Gene therapy Cell Movement Cell Line Tumor medicine Humans Gene silencing lcsh:QD415-436 Neoplasm Metastasis CD44 neoplasms Osteosarcoma biology Cluster of differentiation lcsh:QP1-981 business.industry medicine.disease Meta-analysis Hyaluronan Receptors 030104 developmental biology Microscopy Fluorescence Cell culture Tumor progression 030220 oncology & carcinogenesis biology.protein Cancer research CRISPR-Cas Systems CRISPR-Cas9 business |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 46, Iss 3, Pp 1218-1230 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Metastasis is the major cause of death in patients with osteosarcoma. There is an urgent need to identify molecular markers that promote metastasis. Cluster of differentiation 44 is a receptor for hyaluronic acid (HA) and HA-binding has been proven to participate in various biological tumor activities, including tumor progression and metastasis. Methods: We performed a meta-analysis to investigate the relationship between CD44 expression, survival, and metastasis in patients with osteosarcoma. We then utilized the CRISPR-Cas9 system to specifically silence CD44 in highly metastatic human osteosarcoma cells (MNNG/HOS and 143B) and further determined the functional effects of CD44 knockout in these cells. Results: The meta-analysis demonstrated that a high level of CD44 may predict poor survival and higher potential of metastasis in patients with osteosarcoma. The expression of CD44 in highly metastatic human osteosarcoma cell lines was efficiently blocked by CRISPR-Cas9. When CD44 was silenced, the proliferation and spheroid formation of these osteosarcoma cells was inhibited under 3-D culture conditions. Furthermore, the migratory and invasive functions were also impaired in these highly metastatic osteosarcoma cells. Conclusion: These results suggest that developing new strategies to target CD44 in osteosarcoma may prevent metastasis and improve the clinical outcome of osteosarcoma patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|