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Oncotarget. 2017 Feb 7;8(6):10287-10297. doi: 10.18632/oncotarget.14396.

Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas.

Author information

1
Department of Neurosurgery, The 105th Hospital of PLA, Hefei, Anhui 230000, China.
2
Department of Anesthesiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
3
Department of Pathophysiology, Wannan Medical College, Wuhu 241002, China; Department of Neurosurgery, Wuxi Second People's Hospital, Wuxi, Jiangsu, 214002, China.
4
Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
5
Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100003, China.
6
Department of Neurosurgery, Changzheng Hospital, The Second Hospital affiliated with The Second Military Medical University, Shanghai 200003, China.

Abstract

The clinical prognosis of malignant gliomas is poor and PCDH9 down-regulation is strongly associated with its poor prognosis. But the mechanism of PCDH9 down-regulation is unknown. Abnormal miRNAs profiles regulate tumor phenotypes through inhibiting their target genes and miRNAs could inhibit target genes more efficiently by binding to both the promoter and 3'UTR of target genes. In this study, to search the dual inhibitory miRNAs which suppress PCDH9 expression in gliomas, we performed an integrative analysis of databases including miRDB, TargetScan, microPIR and miRCancer. We identified three candidate miRNAs which were predicted to bind both the promoter and 3'UTR of PCDH9 and up-regulated in gliomas. Then, we validated miR-215-5p up-regulation and PCDH9 down-regulation in glioma samples and demonstrated that miR-215-5p could inhibit the mRNA and protein levels of PCDH9 in glioma cell lines by targeting its promoter and 3' UTR at the same time. Moreover, miR-215-5p could increase glioma cell proliferation, clone formation, in-vitro migration and reduce apoptosis via inhibiting PCDH9 expression. Our study provides evidence for a novel dual inhibition of PCDH9 by miR-215-5p in gliomas and suggests that miR-215-5p might be a therapeutic target for the treatment of gliomas.

KEYWORDS:

PCDH9; glioma; integrative analysis; miR-215-5p; miRNA

PMID:
28055966
PMCID:
PMC5354659
DOI:
10.18632/oncotarget.14396
[Indexed for MEDLINE]
Free PMC Article

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