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.
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Authors | Feng Yan, Le Ying, Xiaofang Li, Bin Qiao, Qiaohong Meng, Liang Yu, Xiangliang Yuan, Shu-Ting Ren, David W Chan, Liyun Shi, Peihua Ni, Xuefeng Wang, Dakang Xu, Yiqun Hu |
Journal | Oncotarget
(Oncotarget)
Vol. 8
Issue 29
Pg. 47020-47036
(Jul 18 2017)
ISSN: 1949-2553 [Electronic] United States |
PMID | 28402947
(Publication Type: Journal Article)
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Chemical References |
- ATF3 protein, human
- Activating Transcription Factor 3
- Biomarkers
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Topics |
- Activating Transcription Factor 3
(genetics, metabolism)
- Aged
- Aged, 80 and over
- Binding Sites
- Biomarkers
- Cell Movement
(genetics)
- Colorectal Neoplasms
(genetics, metabolism, mortality, pathology)
- Computational Biology
(methods)
- Female
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Neoplasm Staging
- Prognosis
- Protein Binding
- Transcriptome
- Tumor Burden
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