title: MiR-506 functions as a tumor suppressor in glioma by targeting STAT3.
abstract: MicroRNA-506 (miR-506) has been reported to act as a tumor suppressive or an oncogenic miRNA in different types of tumors. However, the roles and underlying molecular mechanism of miR-506 in glioma remain unclear. In the present study, we performed quantitative PCR to investigate the level of miR-506 in 36 pairs of glioma tumor and matched adjacent tissues, and found that miR-506 was downregulated in the glioma tumors compared to the expression in the adjacent normal tissues. Furthermore, a functional assay found that ectopic expression of miR-506 in glioma cells markedly suppressed cell proliferation, colony formation, migration and invasion, and suppressed tumor growth in vivo. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-506. Western blot assay showed that overexpression of miR-506 not only induced changes in STAT3 expression but also altered expression of its downstream genes, including, Bcl2, cyclin D1 and matrix metalloproteinase 2 (MMP-2), in the human glioma cells. In addition, STAT3 mRNA expression was increased in the glioma tissues, and was inversely correlated with miR-506. Importantly, overexpression of STAT3 in glioma cells attenuated the suppressive effects of miR-506 on cell proliferation, colony formation, migration and invasion. These results showed that miR-506 functions as a tumor suppressor in glioma by targeting STAT3, suggesting that miR-506 may serve as a potential target in the treatment of human glioma.
authors.affiliation: Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Second Bethune Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Luan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D012334:RNA, Neoplasm / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D014162:Transfection; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C561508:MIRN506 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human