This study evaluated the gene expression of the pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in canine mammary tumors (CMTs), and correlated them with gene expression of miRNAs expected to regulate the secretion of pro-inflammatory cytokines within the tumor microenvironment (TME). Furthermore, gene expression of cytokines and miRNAs involved in tumor cell proliferation and invasion (i.e. miR-21; miR-124; miR-145) were correlated with tumor proliferation index (Ki67 index) to determine the prognostic value in CMTs. Twenty-six canine mammary samples were used, including 22 CMTs and 4 control samples. MiR-21, IL-6 and TNF-alpha were upregulated in mammary carcinomas compared with controls (p < 0.05). MiR-146b was downregulated in CMTs compared with control cases (p < 0.05). IL-6 expression showed a significant positive correlation with miR-21 and a negative correlation with miR-146b; while, TNF-alpha gene expression was positively correlated with miR-21 and miR-145 in mammary carcinomas. In carcinomas, the Ki67 index correlated positively with gene expression of IL-6 and miR-21 and negatively correlated with miR-145 and miR-146b. Specifically, gene expression of IL-6 and miR-21 was positively correlated with ki67 index >33.3%, whereas, expression of miR-145 and miR-146b was negatively correlated with ki67 index <33.3%. Results reinforce the concept of interaction between tumor cells and inflammatory cells within the TME, with a central role of IL-6 and TNF-alpha. Since the upregulation of miR-21 reflects the gene overexpression of interleukins and the high proliferation index of tumor cells, this miRNA may be considered a biomarker with prognostic value in CMTs.

Abbate J.M., Arfuso F., Riolo K., Giudice E., Brunetti B., Lanteri G. (2023). Upregulation of miR-21 and pro-inflammatory cytokine genes IL-6 and TNF-α in promoting a pro-tumorigenic microenvironment in canine mammary carcinomas. RESEARCH IN VETERINARY SCIENCE, 164, 1-11 [10.1016/j.rvsc.2023.105014].

Upregulation of miR-21 and pro-inflammatory cytokine genes IL-6 and TNF-α in promoting a pro-tumorigenic microenvironment in canine mammary carcinomas

Brunetti B.
Penultimo
;
2023

Abstract

This study evaluated the gene expression of the pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in canine mammary tumors (CMTs), and correlated them with gene expression of miRNAs expected to regulate the secretion of pro-inflammatory cytokines within the tumor microenvironment (TME). Furthermore, gene expression of cytokines and miRNAs involved in tumor cell proliferation and invasion (i.e. miR-21; miR-124; miR-145) were correlated with tumor proliferation index (Ki67 index) to determine the prognostic value in CMTs. Twenty-six canine mammary samples were used, including 22 CMTs and 4 control samples. MiR-21, IL-6 and TNF-alpha were upregulated in mammary carcinomas compared with controls (p < 0.05). MiR-146b was downregulated in CMTs compared with control cases (p < 0.05). IL-6 expression showed a significant positive correlation with miR-21 and a negative correlation with miR-146b; while, TNF-alpha gene expression was positively correlated with miR-21 and miR-145 in mammary carcinomas. In carcinomas, the Ki67 index correlated positively with gene expression of IL-6 and miR-21 and negatively correlated with miR-145 and miR-146b. Specifically, gene expression of IL-6 and miR-21 was positively correlated with ki67 index >33.3%, whereas, expression of miR-145 and miR-146b was negatively correlated with ki67 index <33.3%. Results reinforce the concept of interaction between tumor cells and inflammatory cells within the TME, with a central role of IL-6 and TNF-alpha. Since the upregulation of miR-21 reflects the gene overexpression of interleukins and the high proliferation index of tumor cells, this miRNA may be considered a biomarker with prognostic value in CMTs.
2023
Abbate J.M., Arfuso F., Riolo K., Giudice E., Brunetti B., Lanteri G. (2023). Upregulation of miR-21 and pro-inflammatory cytokine genes IL-6 and TNF-α in promoting a pro-tumorigenic microenvironment in canine mammary carcinomas. RESEARCH IN VETERINARY SCIENCE, 164, 1-11 [10.1016/j.rvsc.2023.105014].
Abbate J.M.; Arfuso F.; Riolo K.; Giudice E.; Brunetti B.; Lanteri G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/960032
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