CRIF1 as a potential target to improve the radiosensitivity of osteosarcoma.

ABSTRACT: Resistance to ionizing radiation (IR), which is a conventional treatment for osteosarcoma that cannot be resected, undermines the efficacy of this therapy. However, the mechanism by which IR induces radioresistance in osteosarcoma is not defined. Here, we report that CR6-interacting factor-1 (CRIF1) is highly expressed in osteosarcoma and undergoes nuclear-cytoplasmic shuttling of cyclin-dependent kinase 2 (CDK2) after IR. Osteosarcoma cells lacking CRIF1 show increased sensitivity to IR, which is associated with delayed DNA damage repair, inactivated G1/S checkpoint, and mitochondrial dysfunction. CRIF1 interacts with the DNA damage checkpoint regulator CDK2, and CRIF1 and CDK2 colocalize in the nucleus after IR. Nuclear localization of CDK2 is associated with phosphorylation changes that

SUBMITTER: Ran Q 

PROVIDER: S-EPMC6789918 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature