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MTHFD1L as a folate cycle enzyme correlates with prognostic outcome and its knockdown impairs cell invasive behaviors in osteosarcoma via mediating the AKT/mTOR pathway
Journal of Receptors and Signal Transduction ( IF 2.8 ) Pub Date : 2020-05-26 , DOI: 10.1080/10799893.2020.1769658
Lei Wang 1 , Ya Yang 2 , Xiu-Mei Wang 3 , Cheng-Qun Wang 1 , Yuan-Min Zhang 1 , Bing-Liang Li 1
Affiliation  

Abstract Osteosarcoma (OS) is the most frequent primary malignancy initially in bone with multiple genomic aberrations. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is linked with the progression of diverse tumors. However, its function in OS is not understood completely. The expression pattern and prognostic significance of MTHFD1L in OS tissues were analyzed based on GEO database. The expression level of MTHFD1L in OS cell lines was explored by qRT-PCR. The cell proliferation, colony formation ability, invasion as well as migration in OS cells after MTHFD1L knockdown were determined using cell counting kit 8 (CCK-8) assay, colony formation and transwell methods. GSEA analysis was performed to predict the underlying mechanisms of MTHFD1L in OS development. Furthermore, the western blot was utilized to study the influence of MTHFD1L on AKT/mTOR pathway. Our results indicated that MTHFD1L expression was significantly up-regulated in OS tissues and cells compared with normal tissues and cells. High expression of MTHFD1L could lead to poor prognosis of OS patients. Cell proliferation, colony formation ability, migration and invasion were blocked because of reduced MTHFD1L in vitro. Moreover, cell cycle and AKT/mTOR pathway were all associated with MTHFD1L expression. In conclusion, the findings revealed that MTHFD1L might promote the development of OS via mediating cell cycle and AKT/mTOR pathway, indicating that MTHFD1L might act as a promising therapeutic target for OS treatment.

中文翻译:

MTHFD1L 作为一种叶酸循环酶与预后结果相关,其敲低通过介导 AKT/mTOR 通路损害骨肉瘤中的细胞侵袭行为

摘要 骨肉瘤 (OS) 是最常见的原发性恶性肿瘤,最初发生在骨骼中,具有多种基因组畸变。亚甲基四氢叶酸脱氢酶 1 样 (MTHFD1L) 与多种肿瘤的进展有关。然而,它在操作系统中的功能尚未完全了解。基于GEO数据库分析MTHFD1L在OS组织中的表达模式和预后意义。通过 qRT-PCR 探索 MTHFD1L 在 OS 细胞系中的表达水平。使用细胞计数试剂盒 8 (CCK-8) 测定、集落形成和 transwell 方法测定 MTHFD1L 敲低后 OS 细胞中的细胞增殖、集落形成能力、侵袭和迁移。进行 GSEA 分析以预测 MTHFD1L 在 OS 开发中的潜在机制。此外,利用蛋白质印迹研究MTHFD1L对AKT/mTOR通路的影响。我们的结果表明,与正常组织和细胞相比,MTHFD1L 在 OS 组织和细胞中的表达显着上调。MTHFD1L的高表达可能导致OS患者预后不良。由于体外 MTHFD1L 减少,细胞增殖、集落形成能力、迁移和侵袭被阻断。此外,细胞周期和 AKT/mTOR 通路都与 MTHFD1L 表达相关。总之,研究结果表明 MTHFD1L 可能通过介导细胞周期和 AKT/mTOR 通路促进 OS 的发展,表明 MTHFD1L 可能作为 OS 治疗的有希望的治疗靶点。我们的结果表明,与正常组织和细胞相比,MTHFD1L 在 OS 组织和细胞中的表达显着上调。MTHFD1L的高表达可能导致OS患者预后不良。由于体外 MTHFD1L 减少,细胞增殖、集落形成能力、迁移和侵袭被阻断。此外,细胞周期和 AKT/mTOR 通路都与 MTHFD1L 表达相关。总之,研究结果表明 MTHFD1L 可能通过介导细胞周期和 AKT/mTOR 通路促进 OS 的发展,表明 MTHFD1L 可能作为 OS 治疗的有希望的治疗靶点。我们的结果表明,与正常组织和细胞相比,MTHFD1L 在 OS 组织和细胞中的表达显着上调。MTHFD1L的高表达可能导致OS患者预后不良。由于体外 MTHFD1L 减少,细胞增殖、集落形成能力、迁移和侵袭被阻断。此外,细胞周期和 AKT/mTOR 通路都与 MTHFD1L 表达相关。总之,研究结果表明 MTHFD1L 可能通过介导细胞周期和 AKT/mTOR 通路促进 OS 的发展,表明 MTHFD1L 可能作为 OS 治疗的有希望的治疗靶点。细胞周期和 AKT/mTOR 通路均与 MTHFD1L 表达相关。总之,研究结果表明 MTHFD1L 可能通过介导细胞周期和 AKT/mTOR 通路促进 OS 的发展,表明 MTHFD1L 可能作为 OS 治疗的有希望的治疗靶点。细胞周期和 AKT/mTOR 通路均与 MTHFD1L 表达相关。总之,研究结果表明 MTHFD1L 可能通过介导细胞周期和 AKT/mTOR 通路促进 OS 的发展,表明 MTHFD1L 可能作为 OS 治疗的有希望的治疗靶点。
更新日期:2020-05-26
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