Jin Chi, Feng Yongjian, Ni Yongjian, Shan Zhonglin
The Third Department of Orthopaedics, Central Hospital of Cangzhou City, Cangzhou, Hebei, China.
The Fourth Department of Orthopaedics, Central Hospital of Cangzhou City, Cangzhou, Hebei, China.
Oncotarget. 2017 Apr 11;8(34):56174-56184. doi: 10.18632/oncotarget.17045. eCollection 2017 Aug 22.
Osteosarcoma is the most frequent primary bone tumor affects adolescents and young adults. Recently, microRNAs (miRNAs) are short, non-coding and endogenous RNAs that played as important roles in the initiation and progression of tumors. In this study, we try to explore the biological function and expression of miR-610 in the osteosarcoma. We showed that miR-610 expression was downregulated in the osteosarcoma tissues and cell lines. Elevated expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cycle, invasion and EMT program. Moreover, overexpression of miR-610 increased sensitivity of MG-63 and U2OS cells to cisplatin. Twist1 was identified as a direct target gene of miR-610 in the osteosarcoma cell. Furthermore, we demonstrated that Twist1 was upregulated in the osteosarcoma tissues and cell lines. The expression of Twist1 was negatively associated with the expression of miR-610 expression in the osteosarcoma tissues. Ectopic expression of Twist1 inhibited the sensitivity of miR-610-overexpressing MG-63 cells to cisplatin. We also showed that overexpression of Twist1 increased the proliferation and invasion of miR-610-overexpressing MG-63 cells. These data indicated that ectopic expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cylce, invasion and increased the sensitivity of osteosarcoma cells to cisplatin through targeting the Twist1 expression.
骨肉瘤是最常见的原发性骨肿瘤,好发于青少年和年轻成年人。最近,微小RNA(miRNA)是短的、非编码的内源性RNA,在肿瘤的发生和发展中发挥着重要作用。在本研究中,我们试图探讨miR-610在骨肉瘤中的生物学功能和表达。我们发现miR-610在骨肉瘤组织和细胞系中的表达下调。miR-610表达的升高抑制了骨肉瘤细胞的增殖、细胞周期、侵袭和上皮-间质转化程序。此外,miR-610的过表达增加了MG-63和U2OS细胞对顺铂的敏感性。Twist1被确定为骨肉瘤细胞中miR-610的直接靶基因。此外,我们证明Twist1在骨肉瘤组织和细胞系中上调。Twist1的表达与骨肉瘤组织中miR-610的表达呈负相关。Twist1的异位表达抑制了miR-610过表达的MG-63细胞对顺铂的敏感性。我们还表明,Twist1的过表达增加了miR-610过表达的MG-63细胞的增殖和侵袭。这些数据表明,miR-610的异位表达通过靶向Twist1的表达抑制了骨肉瘤细胞的增殖、细胞周期、侵袭,并增加了骨肉瘤细胞对顺铂的敏感性。