Open AccessCRIF1 as a potential target to improve the radiosensitivity of osteosarcoma
Author(s) -
Qian Ran,
Feng Jin,
Yang Xiang,
Lixin Xiang,
Qiushi Wang,
Fengjie Li,
Li Chen,
Yuan Zhang,
Chun Wu,
Luping Zhou,
Yanni Xiao,
Lili Chen,
Jiang Wu,
Jiang F. Zhong,
Shengwen Calvin Li,
Zhongjun Li
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1906578116
Subject(s) - radioresistance , osteosarcoma , radiosensitivity , cancer research , dna damage , cyclin dependent kinase 2 , dna repair , gene knockdown , g2 m dna damage checkpoint , biology , kinase , chemistry , dna , cell cycle checkpoint , cell cycle , microbiology and biotechnology , radiation therapy , cancer , medicine , apoptosis , protein kinase a , cell culture , biochemistry , genetics
Significance The mechanism of radioresistance in osteosarcoma is unknown. We analyze osteosarcoma patient tissues, combine in vitro and in vivo mouse osteosarcoma models, and determine that CR6-interacting factor-1 (CRIF1) drives radioresistance by regulating the activity of cyclin-dependent kinase 2 (CDK2). After ionizing radiation, CRIF1 promotes CDK2 nuclear translocation and phosphorylation on T14/T160, facilitating G1/S checkpoint activation and DNA damage repair. CRIF1 knockdown enhances the radiosensitivity of osteosarcoma in both in vitro and xenograft models. Our study sheds light on the role of tumor-specific biomarkers in identifying a therapeutic window to overcome radioresistance of osteosarcoma, pointing out a way to precision medicine for a particular patient.
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