a Department of Orthopaedic , The First Affiliated Hospital of Fujian Medical University , Fuzhou , Fujian Province , China.
Artif Cells Nanomed Biotechnol. 2018;46(sup3):S1004-S1010. doi: 10.1080/21691401.2018.1525391. Epub 2018 Nov 19.
EYA2 is the developmental transcription factor and phosphatase, playing an important role in numerous species in regulating cell death and differentiation. Recent studies showed that EYA2 is dysregulated and involved in the progression of various cancers. However, the expression and role of EYA2 in osteosarcoma remains unclear. Here, we found that EYA2 expression was evidently upregulated osteosarcoma (OS) tissue and cell lines. Next, we predicted EYA2-targeting miRNAs, which was further evaluated using a dual luciferase reporter assay. We found that miR-219a-5p significantly repressed EYA2 expression via binding to the 3'-UTR of EYA2. Furthermore, overexpressed miR-219a-5p significantly repressed OS cell invasion and migration, which was reversed by overexpressed EYA2. While silenced miR-219a-5p induced OS cell invasion and migration, which was reversed by silenced EYA2. In conclusion, our study revealed that miR-219a-5p function as tumour suppressor regulates OS cell invasiveness by repressing EYA2 expression.
EYA2 是发育转录因子和磷酸酶，在调节细胞死亡和分化方面在众多物种中发挥着重要作用。最近的研究表明，EYA2 失调并参与了各种癌症的进展。然而，EYA2 在骨肉瘤中的表达和作用尚不清楚。在这里，我们发现 EYA2 在骨肉瘤（OS）组织和细胞系中表达明显上调。接下来，我们预测了 EYA2 靶向的 miRNAs，然后使用双荧光素酶报告基因实验进行了进一步评估。我们发现 miR-219a-5p 通过与 EYA2 的 3'UTR 结合，显著抑制 EYA2 的表达。此外，过表达 miR-219a-5p 显著抑制 OS 细胞的侵袭和迁移，而过表达 EYA2 则逆转了这一作用。而沉默 miR-219a-5p 则诱导 OS 细胞的侵袭和迁移，而过表达 EYA2 则逆转了这一作用。总之，我们的研究表明，miR-219a-5p 通过抑制 EYA2 的表达，作为肿瘤抑制因子发挥作用，调节 OS 细胞的侵袭性。
