Department of Head and Neck and Neurosurgery, Hubei Cancer Hospital, Wuhan, Hubei, China.
Eur Rev Med Pharmacol Sci. 2018 Mar;22(5):1249-1257. doi: 10.26355/eurrev_201803_14465.
Chemoresistance is one of the obstacles for effective treatment of cancers, and recent evidence has shown that microRNAs play critical roles in drug resistance. In this study, we investigated the effect of miR-377 on cisplatin resistance in osteosarcoma (OS).
Tumor tissues from chemoresistant and control OS patients were subjected to Real-time polymerase chain reaction (PCR) to assess miR-377 expression. The effect and mechanism of miR-377 on cisplatin resistance were assessed using Cell Counting Kit (CCK) 8, flow cytometry, Western blot, and luciferase assays in cisplatin-resistant OS cells lines.
Down-regulation of miR-377 was found in chemoresistant OS tissues and cisplatin-resistant OS cell lines. Overexpression of miR-377 re-sensitizes cisplatin resistant OS cells to cisplatin-induced caspase-3 dependent apoptosis. MiR-377 directly represses X-linked inhibitor of apoptosis protein (XIAP) expression through binding to its 3' untranslated region (UTR) of mRNA. Overexpression of XIAP partially cancelled the cisplatin-sensitizing effect of miR-377.
These data uncovered an essential function of miR-377/XIAP signaling axis in regulating cisplatin resistance of OS. MiR-377 may have potential therapeutic values in tackling OS chemoresistance.
化学耐药性是癌症有效治疗的障碍之一，最近的证据表明 microRNAs 在耐药性中发挥关键作用。在这项研究中，我们研究了 miR-377 对骨肉瘤（OS）顺铂耐药性的影响。
用实时聚合酶链反应（PCR）检测化疗耐药和对照 OS 患者的肿瘤组织中 miR-377 的表达。使用细胞计数试剂盒（CCK）8、流式细胞术、Western blot 和荧光素酶测定法在顺铂耐药 OS 细胞系中评估 miR-377 对顺铂耐药性的影响及其机制。
在化疗耐药的 OS 组织和顺铂耐药的 OS 细胞系中发现 miR-377 下调。miR-377 的过表达使顺铂耐药 OS 细胞对顺铂诱导的 caspase-3 依赖性细胞凋亡重新敏感。miR-377 通过与其 mRNA 的 3'非翻译区（UTR）结合，直接抑制 X 连锁凋亡抑制蛋白（XIAP）的表达。XIAP 的过表达部分取消了 miR-377 的顺铂增敏作用。
这些数据揭示了 miR-377/XIAP 信号轴在调节 OS 顺铂耐药性中的重要功能。miR-377 可能在解决 OS 化疗耐药性方面具有潜在的治疗价值。
