Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer
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 incre...
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/2/340 |
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| author | Daniel A. Lujan Joey L. Ochoa Ellen J. Beswick Tamara A. Howard Helen J. Hathaway Nora I. Perrone-Bizzozero Rebecca S. Hartley |
| author_facet | Daniel A. Lujan Joey L. Ochoa Ellen J. Beswick Tamara A. Howard Helen J. Hathaway Nora I. Perrone-Bizzozero Rebecca S. Hartley |
| author_sort | Daniel A. Lujan |
| collection | DOAJ |
| description | 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<sup>+</sup> helper T cells and increased CD8<sup>+</sup> 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. |
| first_indexed | 2024-03-07T22:42:12Z |
| format | Article |
| id | doaj.art-fcacf9eb32fe48378d1920815b64581d |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-07T22:42:12Z |
| publishDate | 2024-02-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-fcacf9eb32fe48378d1920815b64581d2024-02-23T15:08:32ZengMDPI AGBiomedicines2227-90592024-02-0112234010.3390/biomedicines12020340Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast CancerDaniel A. Lujan0Joey L. Ochoa1Ellen J. Beswick2Tamara A. Howard3Helen J. Hathaway4Nora I. Perrone-Bizzozero5Rebecca S. Hartley6Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USADepartment of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USADepartment of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40506, USADepartment of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USADepartment of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USADepartment of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USADepartment of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USARNA 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<sup>+</sup> helper T cells and increased CD8<sup>+</sup> 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.https://www.mdpi.com/2227-9059/12/2/340CIRPPyMTPy2Tbreast cancerinflammation |
| spellingShingle | Daniel A. Lujan Joey L. Ochoa Ellen J. Beswick Tamara A. Howard Helen J. Hathaway Nora I. Perrone-Bizzozero Rebecca S. Hartley Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer Biomedicines CIRP PyMT Py2T breast cancer inflammation |
| title | Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer |
| title_full | Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer |
| title_fullStr | Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer |
| title_full_unstemmed | Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer |
| title_short | Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer |
| title_sort | cold inducible rna binding protein impedes breast tumor growth in the pymt murine model for breast cancer |
| topic | CIRP PyMT Py2T breast cancer inflammation |
| url | https://www.mdpi.com/2227-9059/12/2/340 |
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