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

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.

MicroRNA-379 inhibits cell proliferation and invasion in glioma via targeting metadherin and regulating PTEN/AKT pathway

“…High MTDH expression is also identified as an independent prognostic indicator of the survival of patients with gliomas (40). Previous studies demonstrated that MTDH is involved in the initiation and progression of glioma through the regulation of cell proliferation, colony formation, metastasis, EMT in vitro and decreased tumour growth in vivo (20)(21)(22). Therefore, these findings suggested that MTDH could represent a possible target for the therapy of patients with this deadly disease.…”

“…To delineate the molecular mechanisms by which miR-379 inhibits glioma cell proliferation and invasion, we identified the targets of miR-379 in glioma. Bioinformatics analysis indicated that MTDH, which has been reported to contribute to the initiation and formation of glioma (20)(21)(22), was predicted as a candidate target of miR-379 ( Fig. 3A).…”

CCL18 promotes the metastasis of squamous cell carcinoma of the head and neck through MTDH‐NF‐κB signalling pathway

“…The shown to facilitate the translocation of NF-κB into the nucleus and interacts with the p65 subunit of NF-κB which acts as a coactivator for NF-κB to modulate gene expression of targeted genes. 45,55 Moreover, IκB kinase β-mediated MTDH phosphorylation is critical for IκB-α degradation as well as NF-kB-dependent gene expression and cell proliferation, which correlates with survival in cancer patients. 56 Thus, to summarize, our study demonstrated that serum levels of CCL18 may serve as potential biomarker for diagnosis of SCCHN, and CCL18 plays an important role during invasion, metastasis and EMT of SCCHN.…”

miR‐30e‐5p suppresses cell proliferation and migration in bladder cancer through regulating metadherin

“…21 Some studies reported that MTDH plays an oncogene role in different cancers and promotes cancer growth and metastasis. [22][23][24] MDTH is involved in multiple biological processes of cancer, including cell migration and invasion, differentiation, cell survival and apoptosis, metastasis and even chemotherapy resistant. 25 On the basis of the above evidence, this gene may serve as a practicable target for improving therapies for cancers.…”