RNPC1, an RNA-binding protein and a p53 target, regulates macrophage inhibitory cytokine-1 (MIC-1) expression through mRNA stability.

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.