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MicroRNA-7 targets T-Box 2 to inhibit epithelial-mesenchymal transition and invasiveness in glioblastoma multiforme.
Cancer Letters ( IF 9.1 ) Pub Date : 2020-08-27 , DOI: 10.1016/j.canlet.2020.08.024
Chih-Ming Pan , Kai-Hsiang Chan , Chao-Hsuan Chen , Chia-Ing Jan , Ming-Chao Liu , Chien-Min Lin , Der-Yang Cho , Wan-Chen Tsai , Yen-Tse Chu , Cheng-Hsin Cheng , Hao-Yu Chuang , Shao-Chih Chiu

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.



中文翻译:

MicroRNA-7靶向T-Box 2以抑制多形性胶质母细胞瘤中的上皮-间质转化和侵袭性。

癌症中microRNA表达的失调与上皮-间质转化(EMT)有关,后者触发侵袭能力并增加治疗抵抗力。在这里,我们通过使用microRNA阵列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microRNA表达谱。我们发现在所有肿瘤样品中,microRNA-7(miR-7)始终被下调。使用microRNA.org算法,将T-box 2基因(TBX2)鉴定为miR-7靶向的候选基因。与miR-7相反,TBX2在GBM肿瘤中表达增加,并且与不良预后相关。我们证实在体外GBM细胞过表达miR-7可显着抑制TBX2 mRNA和蛋白质的产生。报告基因检测结果显示,miR-7具有TBX2的3'UTR显着抑制萤光素酶的信号。此外,TBX2过表达降低了E-钙粘着蛋白的表达并增加了波形蛋白的表达,从而在侵袭试验中引起侵袭细胞的数量增加,并且在体内发生肺转移。我们的研究结果表明,通过下调miR-7在GBM肿瘤中TBX2的过表达导致EMT诱导和细胞侵袭增加。

更新日期:2020-08-27
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