Li Xuefeng, Wang Sijia, Chen Yan, Liu Guifeng, Yang Xiaoyu
Department of Anesthesiology, China-Japan Union Hospital, Jilin University, Changchun, China.
Tumour Biol. 2014 Jun;35(6):6021-8. doi: 10.1007/s13277-014-1797-0. Epub 2014 Mar 9.
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.
骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤，频繁获得耐药表型和“继发性恶性肿瘤”的发生通常与化疗相关，并且是实现良好预后的重大障碍。因此，迫切需要确定骨肉瘤化疗耐药的分子机制。在本研究中，我们发现miR-22和高迁移率族蛋白B1（HMGB1）在化疗后的骨肉瘤细胞中表达失调；上调的HMGB1介导自噬并在体外导致骨肉瘤的化疗耐药。然而，可能作为一种补偿效应，miR-22在化疗期间也上调，并且过表达的miR-22靶向HMGB1的3'UTR并抑制HMGB1促进的自噬。我们的研究表明在骨肉瘤化疗耐药期间miR-22和HMGB1对自噬的调节具有复杂性。这些结果揭示了miR-22在骨肉瘤治疗期间对抗化疗耐药的新潜在作用。
