title: RNA over-editing of BLCAP contributes to hepatocarcinogenesis identified by whole-genome and transcriptome sequencing.
abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, although the treatment of this disease has changed little in recent decades because most of the genetic events that initiate this disease remain unknown. To better understand HCC pathogenesis at the molecular level and to uncover novel tumor-initiating events, we integrated RNA-seq and DNA-seq data derived from two pairs of HCC tissues. We found that BLCAP is novel editing gene in HCC and has over-editing expression in 40.1% HCCs compared to adjacent liver tissues. We then used RNA interference and gene transfection to assess the roles of BLCAP RNA editing in tumor proliferation. Our results showed that compared to the wild-type BLCAP gene, the RNA-edited BLCAP gene may stably promote cell proliferation (including cell growth, colony formation in vitro, and tumorigenicity in vivo) by enhancing the phosphorylation of AKT, mTOR, and MDM2 and inhibiting the phosphorylation of TP53. Our current results suggest that the RNA over-editing of BLCAP gene may serve as a novel potential driver in advanced HCC through activating AKT/mTOR signal pathway.
authors.affiliation: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen 518112, China; BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xueda
authors.initials: X
authors.lastname: Hu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Shengqing
authors.initials: S
authors.lastname: Wan
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen 518112, China; Guangdong Key Laboratory of Diagnosis & Treatment for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical college, Shenzhen 518112, China.
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Jialou
authors.initials: J
authors.lastname: Zhu
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Guan
authors.affiliation: BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Jia
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Qiudao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Huang
authors.affiliation: Hepatology Institute of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Liao
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen 518112, China; Guangdong Key Laboratory of Diagnosis & Treatment for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical college, Shenzhen 518112, China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen 518112, China; Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center and National Engineering Center for Biochip at Shanghai, Shanghai, China; Guangdong Key Laboratory of Diagnosis & Treatment for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical college, Shenzhen 518112, China. Electronic address: huangjchgc@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D017393:RNA Editing; D034622:RNA Interference; D017421:Sequence Analysis / Q000379:methods; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics*; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C453739:BLCAP protein, human; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: BLCAP gene; Hepatocarcinogenesis; RNA over-editing; Whole-genome and transcriptome sequencing