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miR-744-5p 通过靶向转化生长因子-β 1 抑制骨肿瘤的发生和转移。

MicroRNA-744-5p suppresses tumorigenesis and metastasis of osteosarcoma through the p38 mitogen-activated protein kinases pathway by targeting transforming growth factor-beta 1.

机构信息

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.

出版信息

Bioengineered. 2022 May;13(5):12309-12325. doi: 10.1080/21655979.2022.2072619.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c8/9276001/3d1b8b2e997f/KBIE_A_2072619_UF0001_B.jpg

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