Department of Orthopedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Cell Mol Med. 2019 Apr;23(4):2280-2292. doi: 10.1111/jcmm.14064. Epub 2019 Feb 5.
Although the application of multiple chemotherapy brought revolutionary changes to improve overall survival of osteosarcoma patients, the existence of multidrug resistance (MDR) has become a great challenge for successful osteosarcoma treatment in recent decades. Substantial studies have revealed various underlying mechanisms of MDR in cancers. As for osteosarcoma, evidence has highlighted that microRNAs (miRNAs) can mediate in the processes of DNA damage response, apoptosis avoidance, autophagy induction, activation of cancer stem cells, and signal transduction. Besides, these drug resistance-related miRNAs showed much promise for serving as candidates for predictive biomarkers of poor outcomes and shorter survival time, and therapeutic targets to reverse drug resistance and overcome treatment refractoriness. This review aims to demonstrate the potential molecular mechanisms of miRNAs-regulated drug resistance in osteosarcoma, and provide insight in translating basic evidence into therapeutic strategies.
尽管多种化疗药物的应用给改善骨肉瘤患者的总体生存率带来了革命性的变化,但近年来多药耐药(MDR)的存在已成为骨肉瘤治疗成功的巨大挑战。大量研究揭示了癌症中 MDR 的各种潜在机制。对于骨肉瘤,有证据表明 microRNAs(miRNAs)可以在 DNA 损伤反应、细胞凋亡逃避、自噬诱导、癌细胞干细胞激活和信号转导过程中发挥作用。此外,这些与耐药相关的 miRNA 作为不良预后和较短生存时间的预测生物标志物候选物,以及逆转耐药和克服治疗抵抗的治疗靶点,具有很大的应用前景。本综述旨在展示 miRNA 调控骨肉瘤耐药的潜在分子机制,并为将基础证据转化为治疗策略提供思路。