Translational Cell Therapy Center, China Medical University Hospital, Taichung, 40447, Taiwan.
Cell Therapy Center, An Nan Hospital, China Medical University, Tainan, 70967, Taiwan; Department of Radiation Oncology, Tainan Municipal An-Nan Hospital-China Medical University, Tainan, 70967, Taiwan.
Cancer Lett. 2020 Nov 28;493:133-142. doi: 10.1016/j.canlet.2020.08.024. Epub 2020 Aug 27.
The dysregulation of microRNA expression in cancer has been associated with the epithelial-mesenchymal transition (EMT) that triggers invasive ability and increases therapeutic resistance. Here, we determined the microRNA expression profile of seven tumor tissues from patients with glioblastoma multiforme (GBM) by use of microRNA array analysis. We discovered that microRNA-7 (miR-7) is consistently downregulated in all tumor samples. Using the microRNA.org algorithm, the T-box 2 gene (TBX2) was identified as a candidate gene targeted by miR-7. In contrast to miR-7, TBX2 had an increased expression in GBM tumors and was linked to poor prognosis. We confirmed that TBX2 mRNA and protein production are significantly repressed by overexpressing miR-7 in GBM cells in vitro. The reporter assay showed that miR-7 significantly represses the signal from luciferase with the 3' UTR of TBX2. Furthermore, TBX2 overexpression decreased E-cadherin expression and increased Vimentin expression, causing an increasing number of invaded cells in the invasion assay, as well as pulmonary metastasis in vivo. Our findings demonstrated that overexpression of TBX2 in GBM tumors via the downregulation of miR-7 leads to EMT induction and increased cell invasion.
miRNA 在癌症中的失调与上皮-间充质转化（EMT）有关，EMT 触发了侵袭能力并增加了治疗抵抗性。在这里，我们通过 miRNA 芯片分析确定了来自多形性胶质母细胞瘤（GBM）患者的七个肿瘤组织的 miRNA 表达谱。我们发现 miRNA-7（miR-7）在所有肿瘤样本中均一致下调。使用 microRNA.org 算法，T 框基因 2（TBX2）被鉴定为 miR-7 的候选靶基因。与 miR-7 相反，TBX2 在 GBM 肿瘤中表达增加，并与不良预后相关。我们在体外证实，miR-7 在 GBM 细胞中过表达可显著抑制 TBX2 的 mRNA 和蛋白生成。报告基因实验表明，miR-7 可显著抑制 TBX2 3'UTR 上的荧光素酶信号。此外，TBX2 的过表达降低了 E-钙粘蛋白的表达，增加了波形蛋白的表达，导致侵袭实验中侵袭细胞数量增加，并在体内引发肺转移。我们的研究结果表明，通过下调 miR-7 导致 EMT 诱导和细胞侵袭增加，从而导致 GBM 肿瘤中 TBX2 的过度表达。
