Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Department of orthopedics, Huizhou Municipal Central Hospital, Huizhou, Guangdong Province, China.
Bioengineered. 2022 May;13(5):12309-12325. doi: 10.1080/21655979.2022.2072619.
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Accumulating evidence has revealed that microRNAs (miRNAs) play a crucial role in the progression of OS. In this study, we found that miR-744-5p was the least expressed miRNA in patients with OS by analyzing GSE65071 from the GENE EXPRESSION OMNIBUS (GEO) database. Through real-time quantitative PCR (qRT-PCR), western blotting, colony formation assay, 5-Ethynyl-2-Deoxyuridine (EdU) incorporation assay, transwell migration, and invasion assays, we demonstrated its ability to inhibit the proliferation, migration, and invasion of OS cells in . According to the luciferase reporter assay, transforming growth factor-β1 (TGFB1) was negatively regulated by miR-744-5p and reversed the effects of miR-744-5p on OS. Subcutaneous tumor-forming animal models and tail vein injection lung metastatic models were used in animal experiments, and it was found that miR-744-5p negatively regulated tumor growth and metastasis in . Furthermore, rescue assays verified that miR-744-5p regulates TGFB1 expression in OS. Further experiments revealed that the p38 MAPK signaling pathway is involved in the miR-744-5p/TGFB1 axis. Generally, this study suggests that miR-744-5p is a negative regulator of TGFB1 and suppresses OS progression and metastasis via the p38 MAPK signaling pathway.
骨肉瘤(OS)是儿童和青少年中最常见的恶性骨肿瘤。越来越多的证据表明,microRNAs(miRNAs)在 OS 的进展中起着关键作用。在这项研究中,我们通过分析 GENE EXPRESSION OMNIBUS(GEO)数据库中的 GSE65071 发现,miR-744-5p 是 OS 患者中表达最低的 miRNA。通过实时定量 PCR(qRT-PCR)、western blot、集落形成实验、5-Ethynyl-2-Deoxyuridine(EdU)掺入实验、Transwell 迁移和侵袭实验,我们证明了它能够抑制 OS 细胞的增殖、迁移和侵袭。根据荧光素酶报告基因实验,转化生长因子-β1(TGFB1)受 miR-744-5p 负调控,并逆转了 miR-744-5p 对 OS 的作用。在动物实验中使用皮下肿瘤形成动物模型和尾静脉注射肺转移模型,发现 miR-744-5p 负调控 OS 中的肿瘤生长和转移。此外,挽救实验验证了 miR-744-5p 调节 OS 中 TGFB1 的表达。进一步的实验表明,p38 MAPK 信号通路参与了 miR-744-5p/TGFB1 轴。总的来说,这项研究表明,miR-744-5p 是 TGFB1 的负调节剂,通过 p38 MAPK 信号通路抑制 OS 的进展和转移。