Wu Xiangkun, Yan Lihua, Liu Yongxi, Xian Wenfeng, Wang Liuyu, Ding Xunmeng
Department of Orthopaedic Surgery, Nanyang Second People's Hospital, Nanyang, Henan, China.
Department of Medical Oncology, Nanyang Second People's Hospital, Nanyang, Henan, China.
PLoS One. 2017 Jun 12;12(6):e0175553. doi: 10.1371/journal.pone.0175553. eCollection 2017.
Osteosarcoma is the most common type of malignant bone tumor, often affecting adolescents and children. MicroRNAs (miRNAs) are a group of small, non-protein coding, endogenous RNAs that play critical roles in osteosarcoma tumorigenesis. In our study, we demonstrated that miR-448 expression was downregulated in osteosarcoma tissues and cell lines. Overexpression of miR-448 suppressed osteosarcoma cell proliferation, colony formation and migration. Moreover, we found that EPHA7 was a direct target gene of miR-448 in osteosarcoma cells. We further demonstrated that the EPHA7 expression level was upregulated in osteosarcoma tissues. Interestingly, the expression level of EPHA7 was inversely correlated with the expression level of miR-448 in osteosarcoma tissues. In addition, elevated expression of miR-448 suppressed osteosarcoma cell proliferation and invasion through targeting EPHA7. Taken together, these findings suggest that miR-448 functioned as a tumor suppressor gene in the development of osteosarcoma through targeting EPHA7.
骨肉瘤是最常见的恶性骨肿瘤类型，常影响青少年和儿童。微小RNA（miRNA）是一类小的、非蛋白质编码的内源性RNA，在骨肉瘤的肿瘤发生过程中发挥关键作用。在我们的研究中，我们证明了miR-448在骨肉瘤组织和细胞系中的表达下调。miR-448的过表达抑制了骨肉瘤细胞的增殖、集落形成和迁移。此外，我们发现EPH A7是骨肉瘤细胞中miR-448的直接靶基因。我们进一步证明，EPH A7在骨肉瘤组织中的表达水平上调。有趣的是，在骨肉瘤组织中，EPH A7的表达水平与miR-448的表达水平呈负相关。此外，miR-448的表达升高通过靶向EPH A7抑制了骨肉瘤细胞的增殖和侵袭。综上所述，这些发现表明miR-448在骨肉瘤的发生发展过程中通过靶向EPH A7发挥肿瘤抑制基因的作用。
