MiRNA-125a-5p inhibits glioblastoma cell proliferation and promotes cell differentiation by targeting TAZ

• DOI: 10.1016/j.bbrc.2014.12.078
• Publication Date: 2014-12-24T04:51:07Z
• Authors: Jian Yuan; Gelei Xiao; Gang Peng; Dingyang Liu; Zeyou Wang; Yiwei Liao; Qing Liu; Minghua Wu; Xianrui Yuan
• Keywords: 0301 basic medicine; Base Sequence; Brain Neoplasms; Molecular Sequence Data; Intracellular Signaling Peptides and Proteins; Cell Differentiation; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Trans-Activators; Humans; RNA, Messenger; Glioblastoma; 3' Untranslated Regions; Cell Proliferation; Genes, Neoplasm; Transcription Factors

Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3' UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells.