title: RNPC1, an RNA-binding protein and a p53 target, regulates macrophage inhibitory cytokine-1 (MIC-1) expression through mRNA stability.
abstract: Macrophage inhibitory cytokine-1 (MIC-1), a secreted cytokine, is a direct target of p53 and known to play a role in cell proliferation, apoptosis, cell metastasis, and angiogenesis through autocrine and paracrine signaling. Previous studies have shown that serum levels of MIC-1 closely parallel cancer progression and are being explored as a diagnostic tool. MIC-1 has also shown potential as a therapeutic agent as it has exhibited several anti-carcinogenic activities. Thus, MIC-1 displays two opposing effects: tumor suppression versus promotion. However, it remains unclear whether MIC-1 is regulated by a mechanism other than transcription and how MIC-1 exerts its tumor suppression. In this study, we show that overexpression of RNA-binding protein RNPC1 can increase, whereas knockdown or knock-out of RNPC1 decreases, MIC-1 transcript and protein levels. Additionally, we demonstrate that RNPC1 can bind to MIC-1 mRNA via an AU-rich element within MIC-1 3'-UTR and then enhances MIC-1 mRNA stability. Finally, to explore the functional significance of MIC-1, we showed that knockdown of MIC-1 can decrease RNPC1-induced cell growth suppression. Altogether, we uncover a novel mechanism by which MIC-1 can be regulated through RNPC1 via mRNA stability.
authors.affiliation: Comparative Oncology Laboratory, University of California, Davis, California 95616, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Yin
authors.forename: Seong-Jun
authors.initials: SJ
authors.lastname: Cho
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D063307:AU Rich Elements / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D055436:Growth Differentiation Factor 15 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D055436:Growth Differentiation Factor 15; C515435:RBM38 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C547649:Rbm38 protein, mouse; D016159:Tumor Suppressor Protein p53
keywords: Cell Proliferation; GDF-15; Gene Regulation; MIC-1; RNA-binding Protein; RNPC1; mRNA Decay; p21; p53