Abstract
Cell invasion is crucial for high mortality and recurrence rate in glioma. Epithelial-mesenchymal 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 glioma-related 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-130b-ceRNAs, providing the first direct link between MTDH and miRNAs in cancer cells.
Highlights
Glioma is the most common and lethal type of primary brain tumor
We found that glioblastoma multiforme (GBM) had higher expression of almost all mesenchymal genes and Epithelialmesenchymal transition (EMT)-TFs but lower expression of epithelial genes compared with normal brain tissues (Figure 1C)
We analyzed the correlation between MTDH and EMT markers and found that MTDH expression was negatively correlated with E-cadherin but positively correlated with Vimentin (Figure 1F and 1G)
Summary
Glioma is the most common and lethal type of primary brain tumor. Tumor cells highly infiltrate and invade into surrounding normal brain tissues, largely accounting for malignant progression and recurrence of glioma, especially for glioblastoma multiforme (GBM) [1]. Exploring the mechanism of EMT-like change in glioma invasion and metastasis will be important to develop effective strategies for glioma treatment. Metadherin (MTDH), known as astrocyteelevated gene-1 (AEG-1) and LYRIC, is an important oncogene that plays a crucial role in the initiation and progression of most malignant tumors [3]. MTDH has been shown to induce EMT in several tumors and promote tumor invasion [6,7,8]
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