Abstract
RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse model of breast cancer, and the effects on both early and late tumorigenesis and inflammation were assessed. The effects of CIRP knockdown were also assessed in Py2T cell grafts. Overexpression of CIRP led to decreased tumorigenesis in the PyMT mouse model. Conversely, the knockdown of CIRP in Py2T cell grafts led to increased tumor growth. Luminex cytokine assays assessed the effects on the inflammatory environment. CIRP/PyMT mammary glands/mammary tumors and serum had decreased cytokines that promote inflammation, angiogenesis, and metastasis compared to PyMT mammary glands and serum, documenting a shift towards an environment less supportive of tumorigenesis. CIRP overexpression also decreased CD4+ helper T cells and increased CD8+ cytotoxic T cells in mammary tumors. Overall, these data support a role for CIRP as a potent antitumor molecule that suppresses both local and systemic pro-tumorigenic inflammation.
Document Type
Article
Publication Date
2-2024
Digital Object Identifier (DOI)
https://doi.org/10.3390/biomedicines12020340
Funding Information
This work was supported, in part, by Dedicated Health Research Funds from the University of New Mexico School of Medicine, the American Association of Anatomists Fellows Grant Award Program, and by the National Institutes of Health Ruth L. Kirschstein National Research Service Award (F31-CA213933). This research was partially supported by UNM Comprehensive Cancer Center Support Grant NCI P30CA118100 and the Flow Cytometry shared resource for usage of the Luminex plate reader and analysis software. Support for the in vivo experiments in this paper was provided by the University of New Mexico Cancer Center Animal Models Shared Resource, funded by the NCI 2P30 CA118100 (PI Willman, C.) “UNM Cancer Center Support Grant”.
Repository Citation
Lujan, Daniel A.; Ochoa, Joey L.; Beswick, Ellen J.; Howard, Tamara A.; Hathaway, Helen J.; Perrone-Bizzozero, Nora I.; and Hartley, Rebecca S., "Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer" (2024). Markey Cancer Center Faculty Publications. 261.
https://uknowledge.uky.edu/markey_facpub/261
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Notes/Citation Information
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).