title: Dual inhibition of PCDH9 expression by miR-215-5p up-regulation in gliomas.
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.
authors.affiliation: Department of Neurosurgery, The 105th Hospital of PLA, Hefei, Anhui 230000, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Wannan Medical College, Wuhu 241002, China; Department of Neurosurgery, Wuxi Second People's Hospital, Wuxi, Jiangsu, 214002, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Shiting
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100003, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Wannan Medical College, Wuhu 241002, China; Department of Neurosurgery, Wuxi Second People's Hospital, Wuxi, Jiangsu, 214002, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Linzhao
authors.initials: L
authors.lastname: Ming
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, The Second Hospital affiliated with The Second Military Medical University, Shanghai 200003, China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Bangbao
authors.initials: B
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001665:Binding Sites; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C553667:MIRN215 microRNA, human; D035683:MicroRNAs; C115817:PCDH9 protein, human; D000091363:Protocadherins; D012333:RNA, Messenger
keywords: PCDH9; glioma; integrative analysis; miR-215-5p; miRNA