title: MicroRNA-126 Inhibits Proliferation, Migration, Invasion, and EMT in Osteosarcoma by Targeting ZEB1.
abstract: Osteosarcoma (OS) is a tumor with rapid progression, high metastatic potential and poor clinical prognosis. This study was aimed to investigate the function of miR-126 in OS cells. The miR-126 expression in OS cell lines and OS tissues were explored by qRT-PCR. Then, the effects of miR-126 on proliferation, cycle, migration, invasion, and transforming growth factor (TGF)-β1 induced epithelial to mesenchymal transition (EMT) were assessed. Predicted by TargetScan, one of target genes for miR-126 was verified by luciferase activity assay. Meantime, the mRNA and protein expressions of ZEB1 were assessed by qRT-PCR and Western blot assay. Subsequently, the effect of ZEB1 silence on miR-126 down-regulated cells was also evaluated. Finally, the expressions of key kinases involved in c-Jun N-terminal kinase (JNK) and Janus-activated kinase (JAK)-1/signal transducer and activator of transcription (STAT)-3 pathways were detected by Western blot analysis. Result showed that miR-126 was down-regulated in OS tissues and cell lines. Overexpression of miR-126 significantly inhibited cell proliferation, migration, invasion, and TGF-β1 induced EMT. The effect of miR-126 knockdown was just the opposite. ZEB1 was predicted and verified as a target gene of miR-126. Meantime, the influence of miR-126 knockdown was abrogated by ZEB1 silence. Additionally, the phosphorylation levels of c-Jun, JNK, JAK1, and STAT3 were down-regulated in miR-126 over-expressed cells, and the effect of miR-126 knockdown was reversed by ZEB1 silence. In conclusion, miR-126 inhibits proliferation, migration, invasion and EMT in OS by targeting ZEB1 through inactivation of JNK and JAK1/STAT3 pathways. J. Cell. Biochem. 118: 3765-3774, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Han
authors.identifier: 0000-0002-5304-4432
authors.initials: H
authors.lastname: Wu
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: C-JUN N-TERMINAL KINASE; EPITHELIAL TO MESENCHYMAL TRANSITION; JANUS-ACTIVATED KINASE (JAK)-1/SIGNAL TRANSDUCER ACTIVATOR OF TRANSCRIPTION (STAT)-3; OSTEOSARCOMA; ZINC FINGER E-BOX BINDING HOMEOBOX 1; miR-126