Cao Riliang, Shao Jianli, Zhang Wencai, Lin Yongxin, Huang Zerong, Li Zhizhong
Department of Orthopedics, First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Tianhe District, Guangzhou, 510630, China.
Discov Oncol. 2021 Jun 1;12(1):18. doi: 10.1007/s12672-021-00412-x.
High expression of long intergenic non-protein coding RNA 987 (LINC00987) is strongly associated with low overall survival of osteosarcoma; however, its role in osteosarcoma remains unclear. This study explored the biological function and underlying mechanism of LINC00987 in osteosarcoma. In this study, LINC00987 expression in osteosarcoma cells was analyzed using Cancer Cell Line Encyclopedia and qRT-PCR. The proliferation and migration and invasion in osteosarcoma cells were evaluated using Cell Counting Kit-8 and Transwell assays, respectively. Bioinformatic analysis was used to predict the LINC00987-bound miRNAs and miR-376a-5p-bound mRNAs. Dual-luciferase reporter assays were used to assess the interaction between miR-376a-5p, LINC00987, and forming-binding protein 1 (FNBP1). FNBP1 expression was measured by western blotting. LINC00987 was found to be upregulated in osteosarcoma cells. LINC00987 silencing suppressed proliferation, migration, and invasion of osteosarcoma cells. Additionally, miR-376a-5p expression was downregulated in osteosarcoma cells. miR-376a-5p knockdown reversed the effect of LINC00987 silencing on the biological function of osteosarcoma cell. miR-376a-5p was found to target LINC00987 and FNBP1. FNBP1protein level was increased in osteosarcoma cells; however, it was inhibited by silencing LINC00987 and enhanced by silencing miR-376a-5p. In conclusions, this study suggests LINC00987 silencing inhibits osteosarcoma cell proliferation, migration, and invasion by sponging miR-376a-5p to regulate FNBP1 expression. LINC00987 as a potential therapeutic target for osteosarcoma.
长链基因间非编码RNA 987（LINC00987）的高表达与骨肉瘤患者的低总生存率密切相关；然而，其在骨肉瘤中的作用仍不清楚。本研究探讨了LINC00987在骨肉瘤中的生物学功能及潜在机制。在本研究中，使用癌症细胞系百科全书和qRT-PCR分析了骨肉瘤细胞中LINC00987的表达。分别使用细胞计数试剂盒-8和Transwell实验评估骨肉瘤细胞的增殖、迁移和侵袭能力。利用生物信息学分析预测与LINC00987结合的miRNA以及与miR-376a-5p结合的mRNA。采用双荧光素酶报告基因实验评估miR-376a-5p、LINC00987和成束蛋白1（FNBP1）之间的相互作用。通过蛋白质免疫印迹法检测FNBP1的表达。研究发现LINC00987在骨肉瘤细胞中表达上调。沉默LINC00987可抑制骨肉瘤细胞的增殖、迁移和侵袭。此外，骨肉瘤细胞中miR-376a-5p的表达下调。敲低miR-376a-5p可逆转LINC00987沉默对骨肉瘤细胞生物学功能的影响。研究发现miR-376a-5p靶向LINC00987和FNBP1。骨肉瘤细胞中FNBP1蛋白水平升高；然而，沉默LINC00987可抑制其表达，而沉默miR-376a-5p则可增强其表达。总之，本研究表明，沉默LINC00987可通过吸附miR-376a-5p来调节FNBP1的表达，从而抑制骨肉瘤细胞的增殖、迁移和侵袭。LINC00987有望成为骨肉瘤的潜在治疗靶点。
