title: Bioinformatic analysis of the membrane cofactor protein CD46 and microRNA expression in hepatocellular carcinoma.
abstract: The therapeutic potential of membrane complement regulatory protein (mCRP)-neutralizing antibodies is unsatisfactory, which perhaps lies in the complex role of mCRPs in tumor occurrence and development. As a member of the mCRPs, CD46 is a transmembrane protein with a cytoplasmic domain and is implicated more in the control of the alternative complement pathway than of the classical complement pathway. Growing evidence has revealed that both the CD46 signaling pathway and microRNAs (miRNAs) play an important role in the development and progression of hepatocellular carcinoma (HCC). In the present study, we analyzed mCRP expression in different tumor tissues by employing western blotting and qPCR. To address the potential role of miRNAs in CD46 signaling, we set out to profile miRNA expression in CD46-overexpressed and -silenced HepG2 cell lines. Furthermore, bioinformatic analysis was performed to identify downstream targets of CD46 signaling. We found that the levels of CD46 expression in HCC tissues were significantly higher compared to that in the adjacent normal tissues. After complement-related gene expression profiling and unsupervised hierarchical clustering analysis of 10 HCC tissues, a total of 37 miRNAs showed significantly different expression levels before and after CD46 expression change. By bioinformatic analysis, we identified let-7b and miR-17 as downstream targets of CD46 signaling, and that the expression levels of let-7b and miR-17 were negatively correlated with that of CD46 in HepG2 cells. The present study suggests that CD46 plays an important role in HCC carcinogenesis by regulating let-7b and miR-17.
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Zejun
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Gynaecology and Obstetrics, The General Hospital of the Chinese People's Armed Police Force, Beijing 100039, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Song
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Ligui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Naval General Hospital of PLA, Beijing 100048, P.R. China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Kang
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Song
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Disease Control and Prevention, Chinese Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Sun
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D051916:Membrane Cofactor Protein / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C497857:CD46 protein, human; C524941:MIRN17 microRNA, human; D051916:Membrane Cofactor Protein; D035683:MicroRNAs; D034741:RNA, Small Interfering; C487931:mirnlet7 microRNA, human