title: MiR-181b-5p downregulates NOVA1 to suppress proliferation, migration and invasion and promote apoptosis in astrocytoma.
abstract: MicroRNAs (miRNAs) are small, short noncoding RNAs that modulate the expression of numerous genes by targeting their mRNA. Numerous abnormal miRNA expression patterns are observed in various human malignancies, and certain miRNAs can act as oncogenes or tumor suppressors. Astrocytoma, the most common neuroepithelial cancer, represents the majority of malignant brain tumors in humans. In our previous studies, we found that the downregulation of miR-181b-5p in astrocytomas is associated with a poor prognosis. The aim of the present study was to investigate the functional role of miR-181b-5p and its possible target genes. miR-181b-5p was significantly downregulated in astrocytoma specimens, and the reduced expression of miR-181b-5p was inversely correlated with the clinical stage. The ectopic expression of miR-181b-5p inhibited proliferation, migration and invasion and induced apoptosis in astrocytoma cancer cells in vitro. The NOVA1 (neuro-oncological ventral antigen 1) gene was further identified as a novel direct target of miR-181b-5p. Specifically, miR-181b-5p bound directly to the 3'-untranslated region (UTR) of NOVA1 and suppressed its expression. In clinical specimens, NOVA1 was overexpressed, and its protein levels were inversely correlated with miR-181b-5p expression. Furthermore, the changing level of NOVA1 was significantly associated with a poor survival outcome. Similar to restoring miR-181b-5p expression, downregulating NOVA1 inhibited cell growth, migration and invasion. Overexpression of NOVA1 reversed the inhibitory effects of miR-181b-5p. Our results indicate that miR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. These findings suggest that miR-181b-5p may serve as a novel therapeutic target for astrocytoma.
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhi
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Danni
authors.initials: D
authors.lastname: Deng
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Naiyuan
authors.initials: N
authors.lastname: Shao
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Suinuan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Xia
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics*; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C000594513:NOVA1 protein, human; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins