Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory

Lasse S. Kristensen (), Karoline K. Ebbesen, Martin Sokol, Theresa Jakobsen, Ulrik Korsgaard, Ann C. Eriksen, Thomas B. Hansen, Jørgen Kjems and Henrik Hager ()
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Lasse S. Kristensen: Aarhus University
Karoline K. Ebbesen: Aarhus University
Martin Sokol: Vejle Hospital
Theresa Jakobsen: Aarhus University
Ulrik Korsgaard: Vejle Hospital
Ann C. Eriksen: Vejle Hospital
Thomas B. Hansen: Aarhus University
Jørgen Kjems: Aarhus University
Henrik Hager: Vejle Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellular expression patterns of ciRS-7 in colon cancer and show that ciRS-7 is completely absent in the cancer cells, but highly expressed in stromal cells within the tumor microenvironment. Additionally, our data suggest that this generally apply to classical oncogene-driven adenocarcinomas, but not to other cancers, including malignant melanoma. Moreover, we find that correlations between circRNA and mRNA expression, which are commonly interpreted as evidence of a ceRNA function, can be explained by different cancer-to-stromal cell ratios among the studied tumor specimens. Together, these results have wide implications for future circRNA studies and highlight the importance of spatially resolving expression patterns of circRNAs proposed to function as ceRNAs.

Date: 2020
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DOI: 10.1038/s41467-020-18355-2

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