title: miR-124 suppresses glioblastoma growth and potentiates chemosensitivity by inhibiting AURKA.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Wanchen
authors.initials: W
authors.lastname: Qiao
authors.affiliation: Department of Neurosurgery, The Fifth Hospital of Daqing City, Daqing, 163711, China.
authors.forename: Beisong
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Acupuncture and Moxibustion, Second Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150001, China.
authors.forename: Haichun
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Wanzhen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. Electronic address: jasper911@sohu.com.
authors.forename: Baijing
authors.initials: B
authors.lastname: Dong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001381:Azepines / Q000008:administration & dosage; D001483:Base Sequence; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D000077204:Temozolomide; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D001381:Azepines; C509207:MIRN124 microRNA, human; C550258:MLN 8237; D035683:MicroRNAs; D011743:Pyrimidines; D003606:Dacarbazine; C576917:AURKA protein, human; D064096:Aurora Kinase A; D000077204:Temozolomide
keywords: AURKA; Glioblastoma; Temozolomide (TMZ); miR-124