Liu Shuheng, Meng Xianghai
Department of Spine Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, Shandong Province, People's Republic of China.
Trauma Center, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, Shandong Province, People's Republic of China.
Onco Targets Ther. 2020 Aug 10;13:7517-7530. doi: 10.2147/OTT.S256464. eCollection 2020.
Osteosarcoma (OS) is a frequently occurring malignancy in children and adolescents. In this study, we aimed to investigate the effects of the long non-coding RNA (lncRNA) LINC00662 (LINC00662) in OS and the underlying molecular mechanism.
The expression of LINC00662, microRNA-15a-5p (miR-15a-5p), and Notch2 in OS was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion of OS cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing, and transwell assay. The interactions among LINC00662, miR-15a-5p, and Notch2 were determined by dual-luciferase reporter assays. A tumor xenograft model was established in mice for evaluating tumor growth in vivo.
The expression of LINC00662 and Notch2 was found to be upregulated in OS, but the expression of miR-15a-5p was downregulated. The results demonstrated that LINC00662 knockdown attenuated the proliferation, migration, and invasion of OS cells and suppressed tumor growth in mice. The study further demonstrated that LINC00662 directly interacted with miR-15a-5p, and that Notch2 was a target of miR-15a-5p. The inhibition of miR-15a-5p or Notch2 overexpression markedly reversed the suppressive effect of sh-LINC00662 on the proliferation, migration, and invasion of OS cells.
The study demonstrated that LINC00662 could be a potential biomarker for OS therapy, and LINC00662 knockdown suppressed the proliferation, migration, and invasion of OS cells by regulating the miR-15a-5p/Notch2 axis.
骨肉瘤（OS）是儿童和青少年中常见的恶性肿瘤。在本研究中，我们旨在探讨长链非编码RNA（lncRNA）LINC00662在骨肉瘤中的作用及其潜在分子机制。
采用定量实时聚合酶链反应（qRT-PCR）检测骨肉瘤中LINC00662、微小RNA-15a-5p（miR-15a-5p）和Notch2的表达。通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）、伤口愈合和Transwell实验分析骨肉瘤细胞的增殖、迁移和侵袭能力。采用双荧光素酶报告基因实验确定LINC00662、miR-15a-5p和Notch2之间的相互作用。在小鼠中建立肿瘤异种移植模型以评估体内肿瘤生长情况。
发现骨肉瘤中LINC00662和Notch2的表达上调，但miR-15a-5p的表达下调。结果表明，敲低LINC00662可减弱骨肉瘤细胞的增殖、迁移和侵袭能力，并抑制小鼠肿瘤生长。该研究进一步表明，LINC00662直接与miR-15a-5p相互作用，且Notch2是miR-15a-5p的靶标。抑制miR-15a-5p或过表达Notch2可显著逆转sh-LINC00662对骨肉瘤细胞增殖、迁移和侵袭的抑制作用。
该研究表明LINC00662可能是骨肉瘤治疗的潜在生物标志物，敲低LINC00662通过调节miR-15a-5p/Notch2轴抑制骨肉瘤细胞的增殖、迁移和侵袭。
