title: Cold-inducible RNA-binding protein promotes epithelial-mesenchymal transition by activating ERK and p38 pathways.
abstract: Transforming growth factor-β1 (TGF-β1), 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-β1-induced EMT models. We found that CIRP overexpression promoted the downregulation of epithelial markers and the upregulation of mesenchymal markers after TGF-β1 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-β1 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.
authors.affiliation: Department of Molecular Medicine, Gachon University Graduate School, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea.
authors.forename: Hae Na
authors.initials: HN
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea; Department of Genome Medicine and Science, College of Medicine, Gachon University, Incheon 21999, Republic of Korea. Electronic address: smahn@gachon.ac.kr.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Department of Molecular Medicine, Gachon University Graduate School, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea; Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea. Electronic address: hhjang@gachon.ac.kr.
authors.forename: Ho Hee
authors.initials: HH
authors.lastname: Jang
mesh_terms: D000072283:A549 Cells; D002465:Cell Movement; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology* / Q000503:physiopathology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: C491390:CIRBP protein, human; D016601:RNA-Binding Proteins
keywords: Cold-inducible RNA-binding protein; E-cadherin; Epithelial-mesenchymal transition; RNA-recognition motif; Snail; Transforming growth factor-β1