Department of Orthopaedics, Ningbo Hwa Mei Hospital, 74519University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
Hum Exp Toxicol. 2020 Dec;39(12):1607-1618. doi: 10.1177/0960327120937330. Epub 2020 Jul 7.
Osteosarcoma is characterized by high malignancy and high metastasis rate, resulting in high mortality and disability. MiR-663a has been reported in a variety of tumors to promote tumorigenesis. However, miR-663a has not been reported in the pathogenesis of osteosarcoma. Bioinformatics analysis and experiments including real-time quantitative polymerase chain reaction (RT-qPCR), luciferase reporter, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, RNA immunoprecipitation, and flow cytometry assay were applied to explore the function and mechanism of miR-663a in MG63, U2OS, Saos-2, SF-86, and hFOB1.19 cells. In this study, we found that miR-663a is highly expressed in osteosarcoma. At the same time, we discovered that miR-663a facilitates cell proliferation and migration, whereas suppresses cell apoptosis in osteosarcoma. Through a series of biological experiments, it was found that miR-663a regulates the cellular process in osteosarcoma by modulating the expression of MYL9. In addition, we also found that long noncoding RNA (lncRNA) GAS5 serves as a molecular sponge for miR-663a and regulates the progression of osteosarcoma via the ceRNA mechanism. We uncover that miR-663a promotes osteosarcoma development through targeting MYL9, which was regulated by lncRNA GAS5.
骨肉瘤具有高度恶性和高转移率的特点,导致高死亡率和残疾率。miR-663a 在多种肿瘤中被报道可促进肿瘤发生。然而,miR-663a 在骨肉瘤的发病机制中尚未被报道。本研究采用生物信息学分析和包括实时定量聚合酶链反应(RT-qPCR)、荧光素酶报告、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)比色法、Western blot、RNA 免疫沉淀和流式细胞术在内的实验,探讨了 miR-663a 在 MG63、U2OS、Saos-2、SF-86 和 hFOB1.19 细胞中的功能和作用机制。在本研究中,我们发现 miR-663a 在骨肉瘤中高表达。同时,我们发现 miR-663a 促进骨肉瘤细胞增殖和迁移,同时抑制细胞凋亡。通过一系列生物学实验,发现 miR-663a 通过调节 MYL9 的表达来调节骨肉瘤中的细胞过程。此外,我们还发现长链非编码 RNA(lncRNA)GAS5 作为 miR-663a 的分子海绵,并通过 ceRNA 机制调节骨肉瘤的进展。我们揭示了 miR-663a 通过靶向 MYL9 促进骨肉瘤的发展,而 MYL9 受 lncRNA GAS5 调控。