Cold‐Inducible RNA Binding Protein (CIRP) In Inflammation and Breast Cancer

Abstract

RNA binding proteins (RBPs) post‐transcriptionally regulate gene expression by associating with the regulatory sequences in the untranslated regions of mRNAs. RBPs are often disrupted in cancer, but current knowledge of their role in regulating cancer‐associated genes is largely based on in vitro studies. This study seeks to determine the in vivo role of cold‐inducible RBP (CIRP), which is overexpressed in some human breast cancers. CIRP promotes cell proliferation and survival and inhibits apoptosis in vitro and promotes inflammation in vivo, all hallmarks of cancer. We tested the hypothesis that CIRP promotes breast tumorigenesis in vivo by crossing a transgenic mouse overexpressing CIRP in the mammary epithelium with the PyMT mouse model of breast cancer. Effects on both early (7‐week‐old mice) and late (14‐week‐old mice) tumorigenesis were assessed. Unexpectedly, mammary glands from 7‐week‐old CIRP/PyMT mice had 50% fewer mammary intraepithelial neoplasias than PyMT mice. Consistent with this, histopathological analysis showed decreased mitosis and increased apoptosis in CIRP/PyMT vs. PyMT mammary glands. Late stage tumorigenesis was also inhibited. CIRP/PyMT mice had slower tumor growth kinetics, smaller tumors, decreased tumor burden and decreased pulmonary metastasis compared to PyMT mice. To assess the mechanism of inhibition, mammary glands from 7 and 14‐week‐old mice were incubated in medium overnight and Luminex cytokine assays were performed on the medium. Results showed a decrease in cytokines that promote inflammation, angiogenesis and metastasis. Altogether, our results suggest that CIRP inhibits proliferation and promotes apoptosis in vivo to suppress early tumorigenesis, potentially via decreasing a protumorigenic inflammatory response.Support or Funding InformationThis work was funded by the University of New Mexico Research Allocation Committee, the American Association of Anatomists Fellows Grant Award Program and by the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award (1 F31 CA213933‐01A1)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.