title: MiR-125a-3p regulates glioma apoptosis and invasion by regulating Nrg1.
abstract: The current study was designed to examine the functional role and mechanism of miR-125a-3p in glioma development. Quantitative RT-PCR was used to evaluate miR-125a-3p expression in 60 glioma cases of different malignant grades. Then, the clinic pathologic significance of miR-125a-3p expression was determined in combination with the prognosis of the patients. In addition, the effects and mechanisms of miR-125a-3p on the proliferation, apoptosis and invasion of glioma cells were further investigated. The results showed that the expression of miR-125a-3p was decreased significantly in most malignant glioma samples relative to normal brain tissues and glioma tissues of low-malignant degree. Further kaplan-meier survival analysis showed that the lower expression of miR-125a-3p was associated with a poor prognosis of GBM patients. Functional analysis showed that the reintroduction of miR-125a-3p into glioblastoma cell lines induces markedly the apoptosis and suppresses the proliferation and migration of glioblastoma cells in vitro and in vivo. Luciferase assay and Western blot analysis revealed that Nrg1 is a direct target of miR-125a-3p. Furthermore, an increased expression of Nrg1 could reverse the effects of overexpression of miR-125a-3p on the proliferation, apoptosis and migration of glioblastoma cells. These findings suggest that miR-125a-3p performed an important role in glioma development mediated by directly regulating the expression of Nrg1. This study also provides a potential target for diagnosis and treatment of malignant glioma.
authors.affiliation: Department of Neurosurgery, the Chinese PLA Navy General Hospital, Beijing, 100048, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yin
authors.affiliation: Department of Neurosurgery, the Chinese PLA Navy General Hospital, Beijing, 100048, China.
authors.forename: Jian Ning
authors.initials: JN
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, the Chinese PLA Navy General Hospital, Beijing, 100048, China.
authors.forename: Shu Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the Chinese PLA Navy General Hospital, Beijing, 100048, China.
authors.forename: Chun Hui
authors.initials: CH
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, the Chinese PLA Navy General Hospital, Beijing, 100048, China.
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Zhao
authors.affiliation: Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Wen Hong
authors.initials: WH
authors.lastname: Fan
authors.affiliation: Department of Brain Protection & Plasticity Research, Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, the Chinese PLA Navy General Hospital, Beijing, 100048, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005910:Glioma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D020890:Neuregulin-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D020890:Neuregulin-1