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Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer

1
Bioneer A/S, Hørsholm, Kogle Allé 2, 2970 Hørsholm, Denmark
2
Danish Colorectal Cancer Center South, Vejle Hospital, Part of Lillebaelt Hospital, Beriderbakken 4, 7100 Vejle, Denmark
3
University Institute of Pathology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark
4
Department of Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Beriderbakken 4, 7100 Vejle, Denmark
5
Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, 5000 Odense C, Denmark
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(8), 1907; https://doi.org/10.3390/ijms20081907
Received: 31 January 2019 / Revised: 9 April 2019 / Accepted: 15 April 2019 / Published: 17 April 2019
(This article belongs to the Special Issue MicroRNA as Biomarkers in Cancer Diagnostics and Therapy)
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Abstract

MicroRNA-21 (miR-21) is upregulated in many cancers including colon cancers and is a prognostic indicator of recurrence and poor prognosis. In colon cancers, miR-21 is highly expressed in stromal fibroblastic cells and more weakly in a subset of cancer cells, particularly budding cancer cells. Exploration of the expression of inflammatory markers in colon cancers revealed tumor necrosis factor alpha (TNF-α) mRNA expression at the invasive front of colon cancers. Surprisingly, a majority of the TNF-α mRNA expressing cells were found to be cancer cells and not inflammatory cells. Because miR-21 is positively involved in cell survival and TNF-α promotes necrosis, we found it interesting to analyze the presence of miR-21 in areas of TNF-α mRNA expression at the invasive front of colon cancers. For this purpose, we developed an automated procedure for the co-staining of miR-21, TNF-α mRNA and the cancer cell marker cytokeratin based on analysis of frozen colon cancer tissue samples (n = 4) with evident cancer cell budding. In all four cases, TNF-α mRNA was seen in a small subset of cancer cells at the invasive front. Evaluation of miR-21 and TNF-α mRNA expression was performed on digital slides obtained by confocal slide scanning microscopy. Both co-expression and lack of co-expression with miR-21 in the budding cancer cells was noted, suggesting non-correlated expression. miR-21 was more often seen in cancer cells than TNF-α mRNA. In conclusion, we report that miR-21 is not linked to expression of the pro-inflammatory cytokine TNF-α mRNA, but that miR-21 and TNF-α both take part in the cancer expansion at the invasive front of colon cancers. We hypothesize that miR-21 may protect both fibroblasts and cancer cells from cell death directed by TNF-α paracrine and autocrine activity. View Full-Text
Keywords: colorectal cancer; confocal slide scanning microscopy; inflammation; interleukin-1β, microRNA; miR-21; TNF-α; tumor budding cells colorectal cancer; confocal slide scanning microscopy; inflammation; interleukin-1β, microRNA; miR-21; TNF-α; tumor budding cells
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Møller, T.; James, J.P.; Holmstrøm, K.; Sørensen, F.B.; Lindebjerg, J.; Nielsen, B.S. Co-Detection of miR-21 and TNF-α mRNA in Budding Cancer Cells in Colorectal Cancer. Int. J. Mol. Sci. 2019, 20, 1907.

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