期刊
JOURNAL OF ORTHOPAEDIC RESEARCH
卷 33, 期 2, 页码 199-207出版社
WILEY
DOI: 10.1002/jor.22745
关键词
osteosarcoma; CRISPR-Cas9; CDK11
类别
资金
- Sarcoma Foundation of America
- National Cancer Institute/National Institutes of Health [UO1 CA 151452-01]
- Sarcoma SPORE/NIH
- Academic Enrichment MGH Orthopaedics
- National Science Foundation China [81101375]
Osteosarcoma is the most common type primary malignant tumor of bone. Patients with regional osteosarcoma are routinely treated with surgery and chemotherapy. In addition, many patients with metastatic or recurrent osteosarcoma show poor prognosis with current chemotherapy agents. Therefore, it is important to improve the general condition and the overall survival rate of patients with osteosarcoma by identifying novel therapeutic strategies. Recent studies have revealed that CDK11 is essential in osteosarcoma cell growth and survival by inhibiting CDK11 mRNA expression with RNAi. Here, we apply the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system, a robust and highly efficient novel genome editing tool, to determine the effect of targeting endogenous CDK11 gene at the DNA level in osteosarcoma cell lines. We show that CDK11 can be efficiently silenced by CRISPR-Cas9. Inhibition of CDK11 is associated with decreased cell proliferation and viability, and induces cell death in osteosarcoma cell lines KHOS and U-2OS. Furthermore, the migration and invasion activities are also markedly reduced by CDK11 knockout. These results demonstrate that CRISPR-Cas9 system is a useful tool for the modification of endogenous CDK11 gene expression, and CRISPR-Cas9 targeted CDK11 knockout may be a promising therapeutic regimen for the treatment of osteosarcoma. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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