title: Krüppel-like factor 4 promotes high-mobility group box 1-induced chemotherapy resistance in osteosarcoma cells.
abstract: Osteosarcoma is the most common primary malignant bone tumor, and the frequent acquisition of chemoresistance is often an obstacle to achieving favorable outcomes during chemotherapy. Recently, Krüppel-like factor 4 (KLF4) has been shown to be associated with chemotherapy resistance in a few tumors; however, the involvement of KLF4 in chemotherapy resistance in osteosarcoma cells remains unknown. In this study, quantitative real-time PCR and western blot analysis revealed that KLF4 expression was significantly increased in response to cisplatin, methotrexate and doxorubicin treatment in osteosarcoma cells, and knockdown of KLF4 increased sensitivity to these anticancer drugs by decreasing cellular clonogenic ability and increasing apoptosis. Moreover, our data suggest that KLF4-regulated drug resistance might, at least partially, positively regulate high-mobility group box 1 (HMGB1), which was found to be a significant contributor to chemoresistance in osteosarcoma cells in our previous study. In summary, this study highlights the significance of KLF4/HMGB1 interaction in regulating chemotherapy resistance, and suggests that targeting KLF4/high-mobility group box 1 may be a therapeutic strategy for osteosarcoma chemotherapy.
authors.affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, The 2nd Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Deye
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Muliang
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First People's Hospital of Xiangtan City, Xiangtan, China.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Orthopaedics, The 2nd Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jiangdong
authors.initials: J
authors.lastname: Ni
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008727:Methotrexate / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate
keywords: Chemotherapy; Krüppel-like factor 4; drug resistance; high-mobility group box 1; osteosarcoma