MicroRNA-7 targets T-Box 2 to inhibit epithelial-mesenchymal transition and invasiveness in glioblastoma multiforme

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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)133-142
Number of pages10
JournalCancer Letters
Volume493
DOIs
Publication statusPublished - Nov 28 2020

Keywords

  • E-Cadherin
  • Invasion
  • miR-7
  • TBX2
  • Vimentin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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