Department of Hand and Foot Microsurgery, Liaoyang Central Hospital, Liaoyang, Liaoning, China.
Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, China.
Cancer Biomark. 2018;23(3):315-322. doi: 10.3233/CBM-170906.
We analyzed the expression of miR-503 in osteosarcoma tissues (OS) and discussed the clinical significance of our findings. To provide a theoretical basis for clinical applications, prognosis prediction and treatment of osteosarcoma, we studied the biological function of miR-503 and its mechanism in MG63 osteosarcoma cells. Real-time polymerase chain reaction (PCR) was used to detect the expression of miR-503 in 45 OS tissues and 20 osteochondroma tumors, analyzing the relationship between clinical pathology and follow-up data. Cox multivariate analysis revealed the clinical and pathological features of the osteosarcoma index and the influence of miR-503 expression on OS prognosis. To observe the effect on cell proliferation and invasion, MG-63 cells were transfected with miR-503. The TargetScan and PicTar bioinformatics method was used to analyze the probable target gene of miR-503 and, combined with the function of the target genes, resulted in a final validation of related pathways. miR-503 was significantly down-regulated in primary OS samples (26/45, 57.8%). The median miR-503 expression level in osteosarcoma was two-fold lower than that in osteochondroma (median expression 6.4 and 13.09, respectively, P< 0.05). The less-expressed miR-503 was associated with Enneking stage (p= 0.004) and invasion (p= 0.015) of OC. Patients with low miR-503 expression had poorer overall survival time. In the multivariate analysis, miR-503 was a significant prognostic factor (P= 0.010). miR-503 can inhibit proliferation and invasion in the MG63 cell line. Using bioinformatics, VEGFA and Rictor were determined to be the likely downstream target genes of miR-503. VEGFA, Rictor, Akt and Erk1/2 were negatively regulated by the overexpression of miR-503. In conclusion, miR-503 has significant tumor-suppressor biological activity and is thus likely to become a new target for the treatment of osteosarcoma.
我们分析了 miR-503 在骨肉瘤组织（OS）中的表达，并讨论了我们研究结果的临床意义。为了为骨肉瘤的临床应用、预后预测和治疗提供理论基础，我们研究了 miR-503 在 MG63 骨肉瘤细胞中的生物学功能及其机制。实时聚合酶链反应（PCR）用于检测 45 例骨肉瘤组织和 20 例骨软骨瘤肿瘤中 miR-503 的表达，分析临床病理与随访资料的关系。Cox 多因素分析揭示了骨肉瘤指数的临床和病理特征以及 miR-503 表达对 OS 预后的影响。为了观察对细胞增殖和侵袭的影响，转染 miR-503 到 MG-63 细胞。TargetScan 和 PicTar 生物信息学方法用于分析 miR-503 的可能靶基因，并结合靶基因的功能，最终验证相关通路。miR-503 在原发性 OS 样本中明显下调（26/45，57.8%）。骨肉瘤中 miR-503 的中位表达水平比骨软骨瘤低两倍（中位表达分别为 6.4 和 13.09，P<0.05）。miR-503 表达较低与 Enneking 分期（p=0.004）和 OC 侵袭（p=0.015）相关。miR-503 低表达的患者总生存时间较差。在多因素分析中，miR-503 是一个显著的预后因素（P=0.010）。miR-503 可抑制 MG63 细胞系的增殖和侵袭。通过生物信息学方法，确定 VEGFA 和 Rictor 为 miR-503 的可能下游靶基因。VEGFA、Rictor、Akt 和 Erk1/2 被 miR-503 的过表达负调控。总之，miR-503 具有显著的肿瘤抑制生物活性，因此可能成为治疗骨肉瘤的新靶点。
