title: MiR-126 Regulates the ERK Pathway via Targeting KRAS to Inhibit the Glioma Cell Proliferation and Invasion.
abstract: The activity of some constitutive contained in the extracellular signal-regulated kinase (ERK) pathway plays crucial roles in glioma cell growth and proliferation. Emerging studies have reported that microRNA (miRNA) could regulate the ERK signal pathway by directly targeting various oncogenes. This study enabled us to discover that the average miR-126 expression was significantly decreased in glioblastoma tissues, and this significant decrease was related to high histopathological grades. Our experiment also demonstrated that the over-expression of miR-126 suppressed glioma cell proliferation and invasion in vitro. Kirsten rat sarcoma viral oncogene (KRAS) which is involved in ERK pathway was directly targeted by miR-126 in glioma through binding to two sites in the 3' untranslated region (3'-UTR) of KRAS mRNA. Notably, the expression level of KRAS was positively correlated to the activity of ERK pathway and its downstream regulators (phosphorylation level of ERK (pERK) and c-Fos). Furthermore, the over-expression of KRAS expression vector without the 3'-UTR partially reverses the tumor-suppressive effects of miR-126. Moreover, the up-regulation of miR-126 contributes to the aberrant activation of the ERK signaling and inhibits cell proliferation and invasion through targeting KRAS. Therefore, it was suspected that miR-126 may be a potential therapeutic target for high-grade glioma.
authors.affiliation: Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Xinmin Street 71, Changchun, 130021, Jilin Province, China.
authors.forename: Yunqian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Xinmin Street 71, Changchun, 130021, Jilin Province, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, Xinmin Street 71, Changchun, 130021, Jilin Province, China. 995541001@qq.com.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Ma
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C117307:KRAS protein, human; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: ERK pathway; Glioma; Invasion; KRAS; Proliferation; miR-126