Tumor Biology

, Volume 37, Issue 7, pp 8487–8502 | Cite as

Understanding the CREB1-miRNA feedback loop in human malignancies

  • Ya-Wen Wang
  • Xu Chen
  • Rong Ma
  • Peng Gao


cAMP response element binding protein 1 (CREB1, CREB) is a key transcription factor that mediates transcriptional responses to a variety of growth factors and stress signals. CREB1 has been shown to play a critical role in development and progression of tumors. MicroRNAs (miRNAs) are a class of non-coding RNAs. They post-transcriptionally regulate gene expression through pairing with the 3′-UTR of their target mRNAs and thus regulate initiation and progression of various types of human cancers. Recent studies have demonstrated that a number of miRNAs can be transcriptionally regulated by CREB1. Interestingly, CREB1 expression can also be modulated by miRNAs, thus forming a feedback loop. This review outlines the functional roles of CREB1, miRNA, and their interactions in human malignancies. This will help to define a relationship between CREB1 and miRNA in human cancer and develop novel therapeutic strategies.


CREB1 miRNA Transcription factor Feedback loop Cancer 



This work was supported by the National Natural Science Foundation of China (No. 81372856) and Taishan Scholars Program of Shandong Province (No. ts201511096). We thank Dr. Hsin-Sheng Yang (Graduate Center for Toxicology, University of Kentucky) and Dr. Tiantian Liu (Department of Pathology, School of Medicine, Shandong University) for their critical reading and suggestions for the manuscript.

Compliance with ethical standards

Conflicts of interest


Supplementary material

13277_2016_5050_MOESM1_ESM.pdf (83 kb)
Online Resource Figure S1 Relationship between CREB1 and miR-27b in gastric cancer, and potential regulation of CREB1 on miR-27b. (a) The expression of CREB1 and miR-27b were detected respectively by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in gastric cancer tissues (for more detail, see our previous paper: Wang et al. Oncotarget. 2015). Spearman’s correlation analysis showed that CREB1 was positively correlated with miR-27b in gastric cancer tissues (r = 0.3563, P = 0.0007). (bc) miRStart ( was utilized to get the putative transcription start sites and promoter sequences of miR-27b. Then the potential biding sites for CREB1 were predicted by RegRNA2.0 ( and PROMO database ( = TF_8.3). The analysis revealed the presence of several CREB1-binding sites in the putative promoter of miR-27b (PDF 83 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of PathologySchool of Medicine, Shandong UniversityJinanPeople’s Republic of China
  2. 2.Department of Breast SurgeryQilu Hospital of Shandong UniversityJinanPeople’s Republic of China

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