Xi'an Jiaotong University Health Science Center, Xi'An City, Shaanxi Province, China.
The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'An City, Shaanxi Province, China.
Life Sci. 2020 May 15;249:117503. doi: 10.1016/j.lfs.2020.117503. Epub 2020 Mar 3.
To investigate the role and mechanism of insulin-like growth factor 1(IGF-1)-mediated EMT on multiple myeloma (MM) growth and metastasis.
The expression data from GEO datasets were utilized to explore the expression levels of IGF-1 and epithelial-mesenchymal transition (EMT) markers in MM. Western blotting and flow cytometry analysis were performed to detect the protein levels of EMT markers as well as key components of the PI3K/Akt pathway. Cell proliferation ability was assessed using colony formation assay and EdU incorporation assays. Transwell migration and invasion assays were performed to assess cell metastasis properties. Vimentin was knocked down by using electro-transfection with small interfering RNA (siRNA) to detect the effect of IGF-1-mediated EMT on MM cell growth and metastasis.
First of all, the analysis of GEO database revealed that IGF-1 was excessively expressed and closely correlated with the expression of the EMT markers in MM patients. Furthermore, we demonstrated that IGF-1 enhanced the acquisition of mesenchymal features in a time-dependent manner. Additionally, in vitro studies revealed that IGF-1-mediated mesenchymal phenotype promoted MM migration, invasion and colony formation. Finally, the mechanism study showed PI3K/Akt signaling pathway was involved in the IGF-1-induced EMT in MM cells.
IGF-1-induced mesenchymal phenotype contributed to MM progression via the PI3K/Akt pathway regulation.
研究胰岛素样生长因子 1（IGF-1）介导的上皮间质转化（EMT）在多发性骨髓瘤（MM）生长和转移中的作用及机制。
利用 GEO 数据集的表达数据，探讨 IGF-1 和 EMT 标志物在 MM 中的表达水平。采用 Western blot 和流式细胞术分析检测 EMT 标志物以及 PI3K/Akt 通路关键成分的蛋白水平。采用集落形成实验和 EdU 掺入实验评估细胞增殖能力。通过 Transwell 迁移和侵袭实验评估细胞转移特性。采用电转染小干扰 RNA（siRNA）敲低波形蛋白，以检测 IGF-1 介导的 EMT 对 MM 细胞生长和转移的影响。
首先，对 GEO 数据库的分析表明，IGF-1 在 MM 患者中过度表达，并与 EMT 标志物的表达密切相关。此外，我们证明 IGF-1 以时间依赖性方式增强了间充质特征的获得。此外，体外研究表明，IGF-1 介导的间充质表型促进了 MM 细胞的迁移、侵袭和集落形成。最后，机制研究表明，PI3K/Akt 信号通路参与了 IGF-1 诱导的 MM 细胞 EMT。
IGF-1 诱导的间充质表型通过 PI3K/Akt 通路的调节促进 MM 的进展。
