title: Targeting CDK11 in osteosarcoma cells using the CRISPR-Cas9 system.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Sarcoma Biology Laboratory, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, 02114, Boston, Massachusetts; Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Avenue, 430022, Wuhan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.forename: Slim
authors.initials: S
authors.lastname: Sassi
authors.forename: Jacson K
authors.initials: JK
authors.lastname: Shen
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Eiji
authors.initials: E
authors.lastname: Osaka
authors.forename: Jianming
authors.initials: J
authors.lastname: Zhang
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mankin
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology
chemical_list: C584437:CDK19 protein, human; D018844:Cyclin-Dependent Kinases
keywords: CDK11; CRISPR-Cas9; osteosarcoma