MicroRNA-7 targets T-Box 2 to inhibit epithelial-mesenchymal transition and invasiveness in glioblastoma multiforme
| Autor: | Chao Hsuan Chen, Chien Min Lin, Yen Tse Chu, Wan Chen Tsai, Der Yang Cho, Hao Yu Chuang, Shao Chih Chiu, Chia-Ing Jan, Kai Hsiang Chan, Chih Ming Pan, Cheng Hsin Cheng, Ming Chao Liu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research Vimentin Mice 03 medical and health sciences 0302 clinical medicine Gentamicin protection assay Downregulation and upregulation Antigens CD Cell Movement Cell Line Tumor microRNA Animals Humans Neoplasm Invasiveness Epithelial–mesenchymal transition 3' Untranslated Regions Cell Proliferation Oligonucleotide Array Sequence Analysis Reporter gene biology Brain Neoplasms MicroRNA Expression Profile Cadherins Prognosis MicroRNA 7 Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Glioblastoma T-Box Domain Proteins Neoplasm Transplantation |
| Zdroj: | Cancer Letters. 493:133-142 |
| ISSN: | 0304-3835 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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