title: miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1β.
abstract: Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor γ coactivator 1β as direct targets of miR-139 and the levels of them were all inversely correlated with miR-139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator-activated receptor γ coactivator 1β-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas.
authors: 1 Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong, University College of Medicine, Xi'an, China.|2 Department of Neurosurgery, the Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China.
authors: Hong
authors: H
authors: Wang
authors: 3 Department of Internal Medicine, Xi'an Dongfang Hospital.
authors: Xi
authors: X
authors: Yan
authors: 4 Department of Neurology, the Affiliated Xi'an Central Hospital of Xi'an Jiaotong, University College of Medicine, Xi'an, China.
authors: Li-Ya
authors: LY
authors: Ji
authors: 5 Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: Xi-Tuan
authors: XT
authors: Ji
authors: 2 Department of Neurosurgery, the Affiliated Xi'an Central Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, China.
authors: Ping
authors: P
authors: Wang
authors: 1 Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong, University College of Medicine, Xi'an, China.
authors: Shi-Wen
authors: SW
authors: Guo
authors: 5 Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors: San-Zhong
authors: SZ
authors: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D016601:RNA-Binding Proteins; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C555098:MIRN139 microRNA, human; C116115:MYCBP protein, human; D035683:MicroRNAs; C455622:PPARGC1B protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: AMY-1; IGF-1 R; PGC-1β; glioma; miR-139; tumor progression