title: MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1.
abstract: The aberrant expression of microRNAs (miRNAs) is always associated with tumor development and progression. Microvascular proliferation is one of the unique pathologic features of glioblastoma (GBM) . In this study, the microvasculature from GBM or normal brain tissue derived from neurosurgeries was purified and total RNA was isolated from purified microvasculature. The difference of miRNA expression profiles between glioblastoma microvasculature and normal brain capillaries was investigated. It was found that miR-7-5p in GBM microvessels was significantly reduced compared with that in normal brain capillaries. In the in vitro experiments, overexpression of miR-7-5p significantly inhibited human umbilical vein endothelial cell proliferation. Forced expression of miR-7-5p in human umbilical vein endothelial cells in vitro significantly reduced the protein level of RAF1 and repressed the activity of the luciferase, a reporter vector carrying the 3'-untranslated region of RAF1. These findings indicate that RAF1 is one of the miR-7-5p target genes. Furthermore, a significant inverse correlation between miR-7-5p expression and RAF1 protein level in GBM microvasculature was found. These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate GBM microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene, implicating an important role for miR-7-5p in the pathogenesis of GBM. It may serve as a guide for the antitumor angiogenesis drug development.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Liu
authors.forename: Lianling
authors.initials: L
authors.lastname: Li
authors.forename: Zhenkuan
authors.initials: Z
authors.lastname: Xu
authors.forename: Baibin
authors.initials: B
authors.lastname: Bi
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian Yi
authors.initials: JY
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D055806:Microvessels / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D019908:Proto-Oncogene Proteins c-raf; C549242:MIRN7-1 microRNA, human