title: Exosomal miR-221 targets DNM3 to induce tumor progression and temozolomide resistance in glioma.
abstract: MicroRNA is an important regulator of glioblastoma. This study aims at validating microRNA-221 (miR-221) as a biomarker for glioblastoma, and understanding how miR-221 regulates glioblastoma progression. Using clinical samples, miR-221 expression was analyzed by quantitative reverse-transcriptase PCR (qPCR). SHG-44 cells were treated with anti-miR-221 or U87MG-derived exosomes followed by monitoring changes in cell viability, migration and temozolomide (TMZ) resistance. Bioinformatics approach was used to identify targets of miR-221. The interaction between miR-221 and its target, DNM3 gene, was studied with dual-luciferase reporter assay, Spearman's correlation analysis, and western blotting. To verify that RELA regulates miR-221 expression, RELA-expressing vector or shRNA was introduced into SHG-44 cells and its effect on miR-221 expression was monitored. Both tissue-level and exosomal miR-221 expression increased with glioma grades. In SHG-44 cells, downregulating miR-221 expression inhibited cell proliferation, migration, and TMZ resistance, whereas incubation with U87MG-derived exosomes exerted tumor-promoting effects. DNM3 gene is a target of miR-221. RELA induced miR-221 expression. In glioma, elevated miR-221 expression is a biomarker for glioma. DNM3 is a target of miR-221 and RELA regulates miR-221 expression. The RELA/miR-221 axis is a target for glioma diagnosis and therapy.
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Jian-Kai
authors.initials: JK
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Ji-Peng
authors.initials: JP
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tong
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Jing
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China.
authors.forename: Guo-Zhu
authors.initials: GZ
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, The Second Hospital of Hebei Medical University, 215 Hepingxi Road, Shijiazhuang, 050000, China. baohuajiao4@163.com.
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Jiao
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D034286:Dynamin III / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D000077204:Temozolomide; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D034286:Dynamin III; D035683:MicroRNAs; D000077204:Temozolomide; D051996:Transcription Factor RelA; C525709:MIR221, human; C498143:RELA protein, human
keywords: DNM3; Drug resistance; Exosome; Glioma; MiR-221; RELA