长链非编码 RNA SNHG12 的下调通过靶向 miR-195-5p 逆转 IGF1R 诱导的骨肉瘤转移和增殖。

Downregulation of lncRNA SNHG12 reversed IGF1R-induced osteosarcoma metastasis and proliferation by targeting miR-195-5p.

机构信息

Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng St, Nangang, Harbin, Heilongjiang 150001, China.

出版信息

Gene. 2020 Feb 5;726:144145. doi: 10.1016/j.gene.2019.144145. Epub 2019 Nov 16.

DOI:10.1016/j.gene.2019.144145

PMID:31743769

Abstract

Long non-coding RNA SNHG12 (lncSNHG12) plays important roles in the onset and progression of various cancers. However, the role of lncSNHG12 in osteosarcoma (OS) remains unclear. Therefore, the aim of the present study was to determine the function of lncSNHG12 in OS. A bioinformatics website was used to predict the downstream targets of lncSNHG12. In addition, qRT-PCR was employed to assess lncSNHG12 expression in OS cells. Cell migration and proliferation in vitro were verified using the transwell migration, clone formation, and CCK8 assays. Tumor metastasis and xenograft formation were monitored in nude mice with or without downregulation of lncSNHG12. The results show that lncSNHG12 was upregulated in OS cell lines. Downregulation lncSNHG12 suppressed the metastasis and proliferation both in vitro and in vivo. Also, lncSNHG12 downregulation suppressed the expression of insulin growth factor 1 receptor (IGF1R) expression through sponging miR-195-5p, which was verified with the luciferase reporter assay and rescue experiments. These findings suggest that downregulation of lncSNHG12 may suppress aggressive OS phenotypes. Moreover, lncSNHG12 silencing inhibited OS metastasis and growth by targeting the miR-195-5p/IGF1R axis, which represents a candidate marker and target for OS treatment and management.

摘要

长链非编码 RNA SNHG12（lncSNHG12）在各种癌症的发生和发展中发挥重要作用。然而，lncSNHG12 在骨肉瘤（OS）中的作用尚不清楚。因此，本研究旨在确定 lncSNHG12 在 OS 中的功能。使用生物信息学网站预测 lncSNHG12 的下游靶标。此外，使用 qRT-PCR 评估 OS 细胞中 lncSNHG12 的表达。通过 Transwell 迁移、克隆形成和 CCK8 测定体外验证细胞迁移和增殖。使用下调 lncSNHG12 的裸鼠监测肿瘤转移和异种移植形成。结果表明，lncSNHG12 在 OS 细胞系中上调。下调 lncSNHG12 抑制了体外和体内的转移和增殖。此外，通过荧光素酶报告基因测定和挽救实验证实，lncSNHG12 下调通过海绵吸附 miR-195-5p 抑制胰岛素生长因子 1 受体（IGF1R）的表达。这些发现表明下调 lncSNHG12 可能抑制侵袭性 OS 表型。此外，lncSNHG12 沉默通过靶向 miR-195-5p/IGF1R 轴抑制 OS 转移和生长，这代表 OS 治疗和管理的候选标志物和靶标。