Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 477, Issue 4, Pages 1038-1044Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.07.028
Keywords
Cold-inducible RNA-binding protein; Transforming growth factor-beta 1; Epithelial-mesenchymal transition; E-cadherin; RNA-recognition motif; Snail
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Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2015R1D1A1A01059919]
- Next-Generation BioGreen 21 Program (SSAC) [PJ01116601]
- Rural Development Administration, Republic of Korea
- National Research Foundation of Korea [2015R1D1A1A01059919] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Transforming growth factor-beta 1 (TGF-beta 1), a potent inducer of epithelial-to-mesenchymal transition (EMT), upregulates the cold-inducible RNA-binding protein (CIRP). The link between CIRP and EMT, however, remains unknown. To determine the role of CIRP in EMT, we performed CIRP knockdown and overexpression experiments in in vitro TGF-beta 1-induced EMT models. We found that CIRP overexpression promoted the downregulation of epithelial markers and the upregulation of mesenchymal markers after TGF-beta 1 treatment for EMT induction. It also promoted cell migration and invasion, key features of EMT. In contrast, CIRP knockdown inhibited the downregulation of epithelial markers and the upregulation of mesenchymal markers after TGF-beta 1 treatment for EMT induction. In addition, it also inhibited cell migration and invasion. Furthermore, we demonstrated that the RNA-recognition motif in CIRP is essential for the role of CIRP in EMT. At the downstream level, CIRP knockdown downregulated Snail, key transcriptional regulator of EMT, while CIRP overexpression upregulated it. We found out that the link between CIRP and Snail is mediated by ERK and p38 pathways. EMT is a critical component of carcinoma metastasis and invasion. As demonstrated in this study, the biological role of CIRP in EMT may explain why CIRP overexpression has been associated with a bad prognosis in cancer patients. (C) 2016 Elsevier Inc. All rights reserved.
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