miR-124 suppresses glioblastoma growth and potentiates chemosensitivity by inhibiting AURKA

• Published in: Biochemical and biophysical research communications 2017-04, Vol.486 (1), p.43-48
• Main Authors: Qiao, Wanchen, Guo, Beisong, Zhou, Haichun, Xu, Wanzhen, Chen, Yongjie, Liang, Yanchao, Dong, Baijing
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions - genetics; 60 APPLIED LIFE SCIENCES; Aged; Antineoplastic Combined Chemotherapy Protocols - pharmacology; AURKA; Aurora Kinase A - antagonists & inhibitors; Aurora Kinase A - genetics; Aurora Kinase A - metabolism; Azepines - administration & dosage; Base Sequence; Blotting, Western; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Dacarbazine - administration & dosage; Dacarbazine - analogs & derivatives; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; GLIOMAS; Humans; INHIBITION; Kaplan-Meier Estimate; Male; MicroRNAs - genetics; Middle Aged; miR-124; PLANT GROWTH; Pyrimidines - administration & dosage; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Sequence Homology, Nucleic Acid; Temozolomide (TMZ); Tumor Burden - drug effects; Tumor Burden - genetics; Xenograft Model Antitumor Assays
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.02.120

Glioblastoma (GBM) accounts for about half of all malignant brain cancers. Although the treatment strategies for glioblastoma develop rapidly, a considerable number of patients could not benefit from temozolomide (TMZ)-based chemotherapy. Here, we revealed a miR-124-AURKA axis that regulated glioblastoma growth and chemosensitivity. Mechanistically, AURKA was up-regulated in glioblastoma tissues and associated with poor overall survival. While overexpression of AURKA enhanced tumor growth, genetic or pharmacological inhibition of AURKA led to growth-inhibitory and chemopotentiating effects in glioblastoma. AURKA was further identified as a target of miR-124. Furthermore, our data showed that miR-124 down-regulated AURKA expression and subsequently suppressed cell growth. Re-expression of AURKA significantly rescued miR124-mediated proliferation repression and chemosensitivity. In conclusion, our results demonstrated that miR-124 inhibited glioblastoma growth and potentiated chemosensitivity by targeting AURKA, which may represent promising targets and rational therapeutic options for glioblastoma. •AURKA was overexpressed and associated with poor OS in GBM.•Targeting AURKA inhibits GBM growth in vitro and in vivo.•AURKA was further identified as a target of miR-124.•Re-expression of AURKA rescued miR-124-mediated growth suppression.