Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Orthopedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China.
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Biomed Pharmacother. 2019 Jun;114:108819. doi: 10.1016/j.biopha.2019.108819. Epub 2019 Apr 2.
Osteosarcoma accounts for about 0.2% in human malignant solid tumors. The mortality and metastatic rates of osteosarcoma remain relatively high. MicroRNA (miRNA) is a kind of non-coding small-molecular RNA discovered in recent years. Various studies have identified the involvement of miRNA in the occurrence and development of tumor as an oncogene or tumor-suppressor gene. This study aims to investigate the effect of hsa-miR-889-3p on the progression of osteosarcoma and its underlying mechanism. Through the bioinformatics methods, we first found that hsa-miR-889-3p was upregulated in osteosarcoma, and it was a prognostic risk factor for osteosarcoma. Additionally, the gene set enrichment analysis (GSEA) revealed that hsa-miR-889-3p mainly affected cell cycle progression and proliferation of osteosarcoma. To verify the bioinformatics results, regulatory effects of hsa-miR-889-3p on osteosarcoma both in vitro and in vivo experiments were investigated. It is found that hsa-miR-889-3p could promote the proliferation of osteosarcoma cells though regulating cell cycle progression. Tumor size and growth rate of osteosarcoma were influenced by hsa-miR-889-3p in xenograft models. To further explore its potential mechanism, the target gene of hsa-miR-889-3p was predicted. Furthermore, hsa-miR-889-3p was confirmed to inhibit the expression of myeloid cell nuclear differentiation antigen (MNDA) in a targeted manner. In conclusion, hsa-miR-889-3p could promote the proliferation of osteosarcoma through inhibiting MNDA expression, which provides a potential therapeutic strategy in treatment for osteosarcoma.
骨肉瘤约占人类恶性实体肿瘤的 0.2%。骨肉瘤的死亡率和转移率仍然相对较高。微小 RNA（miRNA）是近年来发现的一种非编码小分子 RNA。各种研究已经确定 miRNA 作为癌基因或肿瘤抑制基因参与肿瘤的发生和发展。本研究旨在探讨 hsa-miR-889-3p 对骨肉瘤进展的影响及其潜在机制。通过生物信息学方法，我们首先发现 hsa-miR-889-3p 在骨肉瘤中上调，并且是骨肉瘤的预后危险因素。此外，基因集富集分析（GSEA）表明 hsa-miR-889-3p 主要影响骨肉瘤的细胞周期进展和增殖。为了验证生物信息学结果，我们在体外和体内实验中研究了 hsa-miR-889-3p 对骨肉瘤的调节作用。研究发现，hsa-miR-889-3p 可以通过调节细胞周期进程促进骨肉瘤细胞的增殖。异种移植模型中骨肉瘤的肿瘤大小和生长速度受到 hsa-miR-889-3p 的影响。为了进一步探讨其潜在机制，预测了 hsa-miR-889-3p 的靶基因。此外，hsa-miR-889-3p 被证实以靶向方式抑制髓样细胞核分化抗原（MNDA）的表达。总之，hsa-miR-889-3p 通过抑制 MNDA 的表达促进骨肉瘤的增殖，为骨肉瘤的治疗提供了一种潜在的治疗策略。
