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miR-663a 通过靶向 MYL9 促进骨肉瘤的发展,受 lncRNA GAS5 调控。

MiR-663a, regulated by lncRNA GAS5, contributes to osteosarcoma development through targeting MYL9.

机构信息

Department of Orthopaedics, Ningbo Hwa Mei Hospital, 74519University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.

出版信息

Hum Exp Toxicol. 2020 Dec;39(12):1607-1618. doi: 10.1177/0960327120937330. Epub 2020 Jul 7.

Abstract

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.

摘要

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。

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