title: miR-22 targets the 3' UTR of HMGB1 and inhibits the HMGB1-associated autophagy in osteosarcoma cells during chemotherapy.
abstract: Osteosarcoma is the most common malignant bone tumor for children and adolescents, and the frequent acquisition of drug-resistant phenotypes and the occurrence of "secondary malignancies" are often associated with chemotherapy and are significant obstacles to achieving favorable outcomes. Thus, it is urgent to identify the molecular mechanisms underlying the chemoresistance of osteosarcoma. In this study, we showed that miR-22 and high-mobility group box 1 (HMGB1) were deregulated in osteosarcoma cells, post-chemotherapy; the upregulated HMGB1 mediated autophagy and contributed to chemotherapy resistance in osteosarcoma in vitro. However, possibly as a compensatory effect, miR-22 was also upregulated during the chemotherapy, and the overexpressed miR-22 targeted the 3' UTR of HMGB1 and inhibits the HMGB1-promoted autophagy. Our study suggests a complexity in the regulation of autophagy by miR-22 and HMGB1 during chemotherapy resistance in osteosarcoma. These results reveal novel potential role of miR-22 against chemotherapy resistance during the treatment of osteosarcoma.
authors.affiliation: Department of Anesthesiology, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.forename: Sijia
authors.initials: S
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Guifeng
authors.initials: G
authors.lastname: Liu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D024243:HMGB1 Protein; C548375:MIRN22 microRNA, human; D035683:MicroRNAs