title: Overexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer.
abstract: The identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues. In addition, ATF3 overexpression associated with a regulatory molecular signature, and its functions are related to the pathogenic development of CRC. Furthermore, putative ATF3 regulatory elements were identified within the promoters of ATF3 target genes and were confirmed by ChIP-Seq. Critically, in higher ATF3 expression cell lines (HCT116 and RKO) with CRISPR/Cas9 mediated ATF3 knock out, we are able to show that ATF3 target genes such as CEACAM1, DUSP14, HDC, HLF and ULBP2, are required for invasion and proliferation, and they are robustly linked with poor prognosis in CRC. Our findings have important implications for CRC tumorigenesis and may be exploited for diagnostic and therapeutic purposes.
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Tea Science, Zhejiang University, Hangzhou, China.
authors.forename: Le
authors.initials: L
authors.lastname: Ying
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qiao
authors.affiliation: Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China,.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Pathology, School of Basic Medical Science, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Ren
authors.affiliation: Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
authors.forename: David W
authors.initials: DW
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Shi
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Peihua
authors.initials: P
authors.lastname: Ni
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China.|Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia.
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
authors.affiliation: Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Hu
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D015415:Biomarkers; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011485:Protein Binding; D059467:Transcriptome; D047368:Tumor Burden
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D015415:Biomarkers
keywords: ATF3; colorectal cancer; genes signature; prognosis