title: The Downregulation of MicroRNA-146a Modulates TGF-β Signaling Pathways Activity in Glioblastoma.
abstract: Transforming growth factor-β (TGF-β) is considered to be one of the main factors responsible for glioblastoma tumorigenesis. MicroRNAs have recently been shown to regulate cell proliferation, differentiation, and apoptosis. However, the involvement of miRNA-146a in TGF-β1-induced glioblastoma development remains largely unknown. Here, miRNA-164a transfection was used to overexpress miRNA-164a in U87, and then real-time quantitative PCR and Western blot were applied to detect the gene transcription and protein expression. In addition, MTT and wound healing assay were also used to observe cell proliferation and migration. Our data revealed that miRNA-146a was downregulated by TGF-β1 treatment, but upregulated by miRNA-164a transfection. MiRNA-146a overexpression significantly reduced SMAD4 protein expression instead of p-SMAD2. Besides, miRNA-146a overexpression also decreased the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9 as well as the p-ERK1/2 level. Furthermore, the upregulation of miRNA-146a suppressed TGF-β1-mediated U87 proliferation and migration. These results demonstrate that miRNA-146a acts as a novel regulator to modulate the activity and transduction of TGF-β signaling pathways in glioblastoma, and the downregulation of miRNA-146a is required for overexpression of EGFR and MMP9, which can be considered an efficiently therapeutic target and a better understanding of glioblastoma pathogenesis.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, Beijing, China.|School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Shunzeng
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, Beijing, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, Beijing, China.
authors.forename: Congxin
authors.initials: C
authors.lastname: Dai
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Breast Surgery, Peking Union Medical College Hospital, Beijing, China.
authors.forename: Xingtong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, China.|Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Paediatrics, Xiaolan People's Hospital Affiliated to Southern Medical University, Zhongshan, Guangdong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, Beijing, China.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730, Beijing, China. mwbpumch@163.com.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Ma
mesh_terms: D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D066246:ErbB Receptors / Q000096:biosynthesis; D018773:Genes, erbB-1; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D051785:Smad Proteins / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C512478:EGFR protein, human; D066246:ErbB Receptors; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Glioblastoma; MiRNA-146a; Regulation; TGF-β Signaling