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Systematical analysis reveals a strong cancer relevance of CREB1-regulated genes

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  • Tianyu Zheng, Univ Chinese Acad Sci, University of Chinese Academy of Sciences, CAS, Chinese Academy of Sciences, Karolinska Institutet, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Jinrong Huang, BGI-Shenzhen, University of Copenhagen
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  • Xi Xiang, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Siyuan Li, Univ Chinese Acad Sci, University of Chinese Academy of Sciences, CAS, Chinese Academy of Sciences, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Jiaying Yu, University of Chinese Academy of Sciences, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Kunli Qu, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Zhe Xu, Univ Chinese Acad Sci, University of Chinese Academy of Sciences, CAS, Chinese Academy of Sciences, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Peng Han, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Zhanying Dong, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China.
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  • Yang Liu, Univ Chinese Acad Sci, University of Chinese Academy of Sciences, CAS, Chinese Academy of Sciences, BGI-Shenzhen
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  • Fengping Xu, Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, China., BGI-Shenzhen
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  • Huanming Yang, BGI-Shenzhen
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  • Marja Jäättelä, Danish Cancer Society Research Center
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  • Yonglun Luo
  • Bin Liu, Danish Cancer Society Research Center

The transcription factor cyclic-AMP response element-binding protein 1 (CREB1) responds to cAMP level and controls the expression of target genes, which regulates nutrition partitioning. The promoters of CREB1-targeted genes responsive to cAMP have been extensively investigated and characterized with the presence of both cAMP response element and TATA box. Compelling evidence demonstrates that CREB1 also plays an essential role in promoting tumor development. However, only very few genes required for cell survival, proliferation and migration are known to be constitutively regulated by CREB1 in tumors. Their promoters mostly do not harbor any cAMP response element. Thus, it is very likely that CREB1 regulates the expressions of distinct sets of target genes in normal tissues and tumors. The whole gene network constitutively regulated by CREB1 in tumors has remained unrevealed. Here, we employ a systematical and integrative approach to decipher this gene network in the context of both tissue cultured cancer cells and patient samples. We combine transcriptomic, Rank-Rank Hypergeometric Overlap, and Chipseq analysis, to define and characterize CREB1-regulated genes in a multidimensional fashion. A strong cancer relevance of those top-ranked targets, which meet the most stringent criteria, is eventually verified by overall survival analysis of cancer patients. These findings strongly suggest the importance of genes constitutively regulated by CREB1 for their implicative involvement in promoting tumorigenesis.

Original languageEnglish
Article number530
JournalCancer Cell International
Volume21
Issue1
Number of pages16
ISSN1475-2867
DOIs
Publication statusPublished - 2021

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