title: Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt Signaling Pathway.
abstract: CAPON is an adapter protein for nitric oxide synthase 1 (NOS1). CAPON has two isoforms in the human brain: CAPON-L (long form of CAPON) and CAPON-S (short form of CAPON). Recent studies have indicated the involvement of CAPON in tumorigenesis beyond its classical role in NOS1 activity regulation. In this study, we found that the protein levels of CAPON-S, but not than CAPON-L, were significantly decreased in glioma tissues. Therefore, we established lentivirus-mediated stable cell lines with CAPON-S overexpression or down-regulation, and investigated the role of CAPON-S in the proliferation of glioma cells by using CCK8, EdU, and flow cytometry assays. Overexpression of CAPON-S reduced the cell variability and the percentage of EdU-positive cells, and arrested the cells in the G1 phase in glioma cells. Silencing of CAPON by short-hairpin RNA showed the opposite effects. Furthermore, an intracellular signaling array revealed that overexpression of CAPON-S resulted in a remarkable reduction in the phosphorylation of Akt and S6 ribosomal protein in glioma cells, which was further confirmed by Western blot. These findings suggest that CAPON may function as a tumor suppressor in human brain glioma and that the inactivation of the Akt signaling pathway caused by CAPON-S overexpression may provide insight into the underlying mechanism of CAPON in glioma cell proliferation.
authors.affiliation: Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. gaoshangfeng@xzhmu.edu.cn.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. gaoshangfeng@xzhmu.edu.cn.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Gao
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. jiew871@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. zhtfxl@163.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: People's Hospital of Juxian, 100 Fulaizhong Road in Juxian, Rizhao 276500, Shandong, China. lgp123456002@163.com.
authors.forename: Guangping
authors.initials: G
authors.lastname: Liu
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. raycooper@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. 15152118415@163.com.
authors.forename: Daofei
authors.initials: D
authors.lastname: Ji
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. Angelover1314520@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. yunfan661@163.com.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. yunfan661@163.com.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. fugle99@126.com.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. fugle99@126.com.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. yu.rutong@163.com.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-Hai Road, Xuzhou 221002, Jiangsu, China. yu.rutong@163.com.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488081:NOS1AP protein, human; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; CAPON; glioma; mTOR; proliferation