Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas
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Chunlin Wang1,*, Qi Chen2,*, Shu Li3,*, Shiting Li4,*, Zhenyu Zhao5, Hongliang Gao3, Xiaoqiang Wang4, Bin Li4, Wenchuan Zhang4, Yan Yuan4, Linzhao Ming4, Hua He6, Bangbao Tao4, Jun Zhong4
1Department of Neurosurgery, The 105th Hospital of PLA, Hefei, Anhui 230000, China
2Department of Anesthesiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China
3Department of Pathophysiology, Wannan Medical College, Wuhu 241002, China; Department of Neurosurgery, Wuxi Second People’s Hospital, Wuxi, Jiangsu, 214002, China
4Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China
5Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100003, China
6Department of Neurosurgery, Changzheng Hospital, The Second Hospital affiliated with The Second Military Medical University, Shanghai 200003, China
*These authors have contributed equally to the work
Hua He, email: [email protected]
Bangbao Tao, email: [email protected]
Jun Zhong, email: [email protected]
Keywords: PCDH9, miR-215-5p, glioma, miRNA, integrative analysis
Received: March 18, 2016 Accepted: December 12, 2016 Published: December 31, 2016
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.
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