MTDH promotes glioma invasion through regulating miR-130b-ceRNAs
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Liping Tong1,*, Ming Chu2,*, Bingqing Yan1, Weiyi Zhao2, Shuang Liu3, Wei Wei3, Huihuang Lou1, Shengkun Zhang2, Shuai Ma2, Juan Xu4, Lanlan Wei1
1Wu Lien-Teh institute, Department of Microbiology, Harbin Medical University, The Heilongjiang Key Laboratory of Immunity and Infection, Pathogen Biology, Harbin 150081, China
2Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China
3Jiamusi University, Jiamusi 154002, China
4College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, Harbin 150081, China
*These authors contributed equally to this work
Lanlan Wei, email: email@example.com
Juan Xu, email: firstname.lastname@example.org
Keywords: glioma, MTDH, EMT, miR-130b, ceRNA
Received: June 06, 2016 Accepted: December 21, 2016 Published: January 18, 2017
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.
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