Department of Orthopaedics, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5713-5721. doi: 10.3892/mmr.2017.7249. Epub 2017 Aug 14.
MicroRNAs (miRNAs/miRs) have been implicated in the development and progression of osteosarcoma. miR-448 is emerging as a tumor-associated miRNA in many human cancers. However, the role of miR‑448 in osteosarcoma remains unknown. The present study aimed to identify the potential role of miR‑448 in osteosarcoma. It was demonstrated that miR‑448 was significantly downregulated in osteosarcoma cell lines, as detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). miR‑448 mimics were transfected into osteosarcoma cells to overexpress miR‑448. Overexpression of miR‑448 markedly inhibited cell proliferation and invasion in osteosarcoma cells. Bioinformatics and luciferase reporter assays demonstrated that astrocyte elevated gene‑1 (AEG‑1) was a target gene of miR‑448. RT‑qPCR and western blot analysis revealed that miR‑448 inhibited AEG‑1 expression. Further data revealed that miR‑448 overexpression impeded the Wnt and nuclear factor‑κB signaling pathways. However, restoration of AEG‑1 expression could abolish the miR‑448‑mediated antitumor effects. Taken together, these findings suggested that miR‑448 may inhibit osteosarcoma development by targeting AEG‑1, providing a novel candidate miRNA for development of miRNA‑targeted therapies for osteosarcoma.
微小 RNA(miRNAs/miRs)已被牵涉到骨肉瘤的发生和发展中。miR-448 作为一种肿瘤相关 miRNA 已在许多人类癌症中显现出来。然而,miR-448 在骨肉瘤中的作用仍不清楚。本研究旨在确定 miR-448 在骨肉瘤中的潜在作用。研究表明,miR-448 在骨肉瘤细胞系中显著下调,这通过逆转录-定量聚合酶链反应(RT-qPCR)检测到。将 miR-448 模拟物转染到骨肉瘤细胞中以过表达 miR-448。miR-448 的过表达显著抑制骨肉瘤细胞的增殖和侵袭。生物信息学和荧光素酶报告基因检测表明,星形细胞瘤上调基因 1(AEG-1)是 miR-448 的靶基因。RT-qPCR 和 Western blot 分析显示 miR-448 抑制 AEG-1 的表达。进一步的数据表明 miR-448 过表达阻碍了 Wnt 和核因子-κB 信号通路。然而,AEG-1 表达的恢复可以消除 miR-448 介导的抗肿瘤作用。综上所述,这些发现表明 miR-448 可能通过靶向 AEG-1 抑制骨肉瘤的发展,为骨肉瘤的 miRNA 靶向治疗提供了一个新的候选 miRNA。