title: CRNDE affects the malignant biological characteristics of human glioma stem cells by negatively regulating miR-186.
abstract: The long non-coding RNA Colorectal neoplasia differentially expressed (CRNDE) is a novel gene that activated early in colorectal neoplasia, but it is also up-regulated in many other solid tumors. Herein, the function and underlying mechanism of CRNDE in regulating glioma stem cells (GSCs) were investigated. We found that CRNDE expression was up-regulated while miR-186 expression was down-regulated in GSCs. Overexpression of CRNDE could promote the cellular proliferation, migration, invasion and inhibit the apoptosis in GSCs. Overexpression of miR-186 exerted functions of inhibiting the proliferation, migration and invasion of GSCs and promoting apoptosis. And CRNDE decreased the expression levels of XIAP and PAK7 by binding to miR-186 and negatively regulating it. In addition, miR-186 binded to XIAP and PAK7 3'UTR region, and decrease the expression of them, thus regulating the expression levels of downstream target proteins such as caspase 3, BAD, cyclin D1 and MARK2. The in vivo effect of CRNDE and miR-186 showed that the tumor formation rate was minimum in tumor-bearing nude mice with the knockdown of CRNDE and the overexpression of miR-186. In conclusion, CRNDE played an oncogenic role of GSCs through the negative regulation of miR-186. Both CRNDE and miR-186 could be regarded as potential targets in the glioma therapy.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Xiao-bai
authors.initials: XB
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Yi-xue
authors.initials: YX
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, China.|Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China.
authors.forename: Zhi-qing
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: Department of Physiology, College of Basic Medicine, China Medical University, Shenyang 110001, China.
authors.forename: Zhen-hua
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yun-hui
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C586983:CRNDE RNA, human; C533096:MIRN186 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C443802:PAK5 protein, human; D054462:p21-Activated Kinases
keywords: CRNDE; glioma stem cells; long non-coding RNAs; miR-186; microRNAs