Overexpression of the transcription factor ATF3 with a regulatory molecular signature associates with the pathogenic development of colorectal cancer.
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.
['Yan|Feng|F|', 'Ying|Le|L|', 'Li|Xiaofang|X|', 'Qiao|Bin|B|', 'Meng|Qiaohong|Q|', 'Yu|Liang|L|', 'Yuan|Xiangliang|X|', 'Ren|Shu-Ting|ST|', 'Chan|David W|DW|', 'Shi|Liyun|L|', 'Ni|Peihua|P|', 'Wang|Xuefeng|X|', 'Xu|Dakang|D|', 'Hu|Yiqun|Y|']
D051700:Activating Transcription Factor 3 D000368:Aged D000369:Aged, 80 and over D001665:Binding Sites D015415:Biomarkers D002465:Cell Movement D015179:Colorectal Neoplasms D019295:Computational Biology 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
ATF3 colorectal cancer prognosis genes signature