Department of Orthopaedics, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2017 Nov;38(5):2993-3000. doi: 10.3892/or.2017.5983. Epub 2017 Sep 21.
An increasing number of studies have demonstrated that microRNAs participate in the development of osteosarcoma by acting as tumour suppressor or tumour-promoting genes. We investigated the role of miR-504 in the growth and metastasis of osteosarcoma. The expression of miR-504 in clinical osteosarcoma samples was higher than that in the adjacent normal tissue and correlated with tumour size and clinical stage. Tumour protein p53-inducible nuclear protein 1 (TP53INP1) was downregulated in the clinical osteosarcoma samples compared with the adjacent normal tissues and was consistently correlated with the clinical stage. The results of dual-luciferase reporter assay and western blot analysis demonstrated that the TP53INP1 gene is a direct target of miR-504. Altogether, the Cell Counting Kit-8 (CCK-8), the colony formation, the flow cytometry and the Transwell assay results demonstrated that miR-504 promoted osteosarcoma cell growth and metastasis in vitro. P73, P21, Bax, cleaved-caspase-3 and secreted protein acidic and rich in cysteine (SPARC) were associated with the suppressive role of miR-504/TP53INP1. The overexpression of miR-504 in osteosarcoma xenografts enhanced the tumour growth and increased the metastatic burden. Collectively, these results revealed that TP53INP1 is a target gene of miR-504 and that miR-504 enhances osteosarcoma growth and promotes distant metastases by targeting TP53INP1. Thus, miR-504/TP53INP1 may be associated with osteosarcoma size and clinical stage.
越来越多的研究表明，microRNAs 通过作为肿瘤抑制基因或肿瘤促进基因参与骨肉瘤的发生发展。我们研究了 miR-504 在骨肉瘤生长和转移中的作用。miR-504 在临床骨肉瘤样本中的表达高于相邻正常组织，且与肿瘤大小和临床分期相关。与相邻正常组织相比，肿瘤蛋白 p53 诱导核蛋白 1（TP53INP1）在临床骨肉瘤样本中下调，且与临床分期一致。双荧光素酶报告基因检测和 Western blot 分析结果表明，TP53INP1 基因是 miR-504 的直接靶基因。总之，细胞计数试剂盒-8（CCK-8）、集落形成、流式细胞术和 Transwell 检测结果表明，miR-504 促进骨肉瘤细胞在体外的生长和转移。p73、p21、Bax、cleaved-caspase-3 和富含半胱氨酸的酸性分泌蛋白（SPARC）与 miR-504/TP53INP1 的抑制作用有关。骨肉瘤异种移植中 miR-504 的过表达增强了肿瘤生长并增加了转移负担。总之，这些结果表明，TP53INP1 是 miR-504 的靶基因，miR-504 通过靶向 TP53INP1 增强骨肉瘤的生长并促进远处转移。因此，miR-504/TP53INP1 可能与骨肉瘤的大小和临床分期有关。
