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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.<\/jats:p>","DOI":"10.1073\/pnas.1906578116","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T20:36:18Z","timestamp":1569270978000},"page":"20511-20516","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["CRIF1 as a potential target to improve the radiosensitivity of osteosarcoma"],"prefix":"10.1073","volume":"116","author":[{"given":"Qian","family":"Ran","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion, Laboratory of Radiation Biology, The Second Affiliated Hospital, Third Military Medical University, 400037 Chongqing, China;"},{"name":"Division of Periodontology, Diagnostic Sciences and Dental Hygiene and Biomedical Sciences, Ostrow School of 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