title: MicroRNA-106b-5p boosts glioma tumorigensis by targeting multiple tumor suppressor genes.
abstract: Aberrant expression of microRNAs (miRNAs) has been implicated in cancer initiation and progression. However, little is known about the potential role of miRNAs in glioma tumorigenesis. In this study, we found that miRNA-106b-5p was significantly upregulated in glioma tumor samples and cell lines compared with normal brain tissues, and its expression level correlated with the pathological grading. Overexpression of miR-106b-5p in glioma tumor cells significantly promoted cell proliferation, although inhibited cell apoptosis in vitro and in vivo. In contrast, knockdown of miR-106b-5p significantly inhibited cell proliferation, although enhanced cell apoptosis. Mechanistic study revealed that two target genes, retinoblastoma-like 1 (RBL1) and RBL2, were involved in miR-106b-5p's regulation of cell proliferation and one target gene, caspase-8 (CASP8), mediated miR-106b-5p's regulation of apoptosis. We also investigated the function of the three targets in glioma tumorigenesis by RNA interference manipulation and demonstrated that knockdown of these target genes led to cell proliferation enhancement or cell apoptosis inhibition in vitro. More interestingly, the expression levels of these targets were significantly downregulated in glioma samples and knockdown of these targets in glioma cells inhibited the xenograft tumor formation in vivo. Moreover, we verified the regulation function of miR-106b-5p and its targets on cell proliferation and apoptosis of the primary cultured astrocytes isolated from glioma tumor samples and healthy controls. Collectively, our findings show the critical roles of miR-106b-5p and its targets, RBL1, RBL2 and CASP8, in glioma tumorigenesis and provide potential candidates for malignant glioma therapy.
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: F
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of neurosurgery, Changzhou NO.2 People's Hospital, Changzhou, Jiangsu, China.
authors.forename: B
authors.initials: B
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D034622:RNA Interference; D050720:Retinoblastoma-Like Protein p107 / Q000235:genetics / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130 / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden
chemical_list: C542541:MIRN106 microRNA, human; D035683:MicroRNAs; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; C505530:CASP8 protein, human; D053181:Caspase 8