MicroRNA-139-3p suppresses growth and metastasis of glioblastoma via inhibition of NIN1/RPNI2 binding protein 1 homolog

L. Shi, Y. Yuan , H.-Y. Li

Department of Neurosurgery, Dezhou People’s Hospital, Dezhou, Shandong, China. lihongyuanlhy@tom.com

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• Oncology

OBJECTIVE: This study aimed to investigate the role of microRNA-139-3p (miR-139-3p) in glioblastoma, and further explored the underlying molecular mechanism.
PATIENTS AND METHODS: Gene Expression Omnibus (GEO) dataset (accession code GSE90603) was selected to identify differentially expressed microRNAs in glioblastoma. The level of miR-139-3p in glioblastoma tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), colony formation, wound healing, and transwell invasion assays were applied to assess the role of miR-139-3p in glioblastoma cells growth and aggressiveness. The direct target of miR-139-3p was confirmed using luciferase reporter assay. NIN1/RPNI2 binding protein 1 homolog (NOB1), specific short hairpin RNA (shRNA), and lentiviral vector encoding NOB1 stable transfections were done. The expression levels of NOB1 were detected by Western blotting and qRT-PCR. Glioblastoma cells were subcutaneously implanted into nude mice to determine the role of miR-139-3p in tumor growth and metastasis in vivo.
RESULTS: miR-139-3p was remarkably down-expressed in glioblastoma tissue compared to control normal tissue. Overexpression of miR-139-3p suppressed the growth and metastasis of glioblastoma cells. Moreover, miR-139-3p inhibited glioblastoma growth and lung metastasis in vivo, whereas under-expression of miR-139-3p caused an opposite outcome. Furthermore, our work revealed that NOB1 expression was negatively associated with miR-139-3p, and NOB1 knock-down mimicked the inhibitory effect of miR-139-3p on glioblastoma cell proliferation and mobility phenotypes. Finally, overexpression of NOB1 neutralized the inhibition of miR-139-3p in glioblastoma cells.
CONCLUSIONS: Our findings indicated that miR-139-3p played a vital role in inhibiting glioblastoma growth and metastasis by targeting NOB1.

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