MTDH promotes glioma invasion through regulating miR-130b-ceRNAs

作者:Tong, Liping; Chu, Ming; Yan, Bingqing; Zhao, Weiyi; Liu, Shuang; Wei, Wei; Lou, Huihuang; Zhang, Shengkun; Ma, Shuai; Xu, Juan*; Wei, Lanlan*
来源:Oncotarget, 2017, 8(11): 17738-17749.
DOI:10.18632/oncotarget.14717

摘要

Cell invasion is crucial for high mortality and recurrence rate in glioma. Epithelialmesenchymal transition (EMT) is an important step in cancer invasion. Metadherin (MTDH) contributes to EMT in several cancers, but the role and mechanism of MTDH in EMT-like process of glioma remain unknown. Here we demonstrate that MTDH was overexpressed in glioma tissues and cells and induced EMT-like change and invasion of glioma cells. Interestingly, MTDH could modulate the expression of a group of gliomarelated miRNAs. In particular, MTDH upregulated miR-130b transcription via acting as a coactivator of NF-kB. MiR-130b promoted EMT-like change and invasion of glioma cells through targeting multiple EMT-related genes, including PTEN, PPP2CA and SMAD7. In addition, PTEN acted as the competing endogenous RNA (ceRNA) to affect PPP2CA and SMAD7 expression, and inhibited EMT-like change in glioma cells. Furthermore, miR-130b mediated EMT-like change induced by MTDH, and MTDH inhibited the expression levels of PTEN, PPP2CA and SMAD7. Taken together, we reveal a novel mechanism that MTDH induces EMT-like change and invasion of glioma via the regulation of miR-130bceRNAs, providing the first direct link between MTDH and miRNAs in cancer cells.