title: MiR-203 sensitizes glioma cells to temozolomide and inhibits glioma cell invasion by targeting E2F3.
abstract: Glioma is the most common malignant and fatal primary tumor in the central nervous system in adults. Recent data has suggested a profound role for microRNAs (miRs) in cancer progression. The present study demonstrated, via quantitative polymerase chain reaction (qPCR) analysis, that miR-203 expression was markedly lower in highly invasive U87MG glioma cells and glioma tissues. Wound healing and Transwell assays demonstrated that restoration of miR-203 expression inhibited U87MG cell migration and invasion. Restoration of miR-203 expression additionally sensitized the cells to temozolomide (TMZ) as determined by MTS assay. By contrast, miR-203 inhibition in A172 cells exerted opposite effects. Bioinformatic analysis combined with experimental analysis revealed that miR-203 directly targeted E2F3 via the conserved miR-203 target site within the E2F3 3'-untranslational region. E2F3 knockdown with specific small hairpin RNA also inhibited U87MG cell migration and invasion, and sensitized them to TMZ. Importantly, miR-203 and E2F3 showed inverse expression patterns in invasive glioma tissues, as demonstrated by qPCR and luciferase assay. These results suggested that miR-203 may function as a tumor suppressor in glioma progression and that the miR-203/E2F3 axis may be a novel candidate in the development of rational therapeutic strategies for glioma.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Gelei
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huo
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D050699:E2F3 Transcription Factor / Q000737:chemistry / Q000235:genetics*; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D034622:RNA Interference; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D050699:E2F3 Transcription Factor; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D003606:Dacarbazine; D000077204:Temozolomide