title: MiR224-3p inhibits hypoxia-induced autophagy by targeting autophagy-related genes in human glioblastoma cells.
abstract: Human glioblastoma multiforme (GBM) is a malignant solid tumor characterized by severe hypoxia. Autophagy plays a protective role in cancer cells under hypoxia. However, the microRNA (miRNA)-related molecular mechanisms underlying hypoxia-reduced autophagy remain poorly understood in GBM. In this study, we performed a miRNA microarray analysis on GBM cells and found that numerous miRNAs were differentially expressed under hypoxic conditions. Further research showed that miR224-3p, one of the significantly down-regulated miRNAs, was involved in regulating hypoxia-induced autophagy in GBM cells. Overexpression of miR224-3p abolished hypoxia-induced autophagy, whereas knocking down endogenous miR224-3p increased autophagic activity under normoxia. In addition, we demonstrated that miR224-3p inhibited autophagy by directly suppressing the expression of two autophagy-related genes (ATGs), ATG5 and FAK family-interacting protein of 200 kDa (FIP200). Furthermore, in vitro, miR224-3p attenuated cell proliferation and promoted hypoxia-induced apoptosis, and in vivo, overexpression of miR224-3p inhibited tumorigenesis of GBM cells. Collectively, our study identified a novel hypoxia-down-regulated miRNA, miR224-3p, as a key modulator of autophagy by inhibiting ATGs in GBM cells.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Dezhou People's Hospital, Dezhou, Shandong Province, P.R. China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, P.R. China.|Brian Science Research Institute, Shandong University, Jinan, Shandong Province, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D059016:Tumor Microenvironment
chemical_list: D020413:3' Untranslated Regions; C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C407704:RB1CC1 protein, human; D011505:Protein-Tyrosine Kinases
keywords: autophagy; autophagy-related genes; glioblastoma; hypoxia; microRNAs