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; Henrik Hager

doi:10.1038/s41467-020-18355-2

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, Henrik Hager

^*Corresponding author for this work

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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.

Original language	English
Article number	4551
Journal	Nature Communications
Volume	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-020-18355-2
Publication status	Published - Dec 2020

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

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.",

author = "Kristensen, {Lasse S.} and Ebbesen, {Karoline K.} and Martin Sokol and Theresa Jakobsen and Ulrik Korsgaard and Eriksen, {Ann C.} and Hansen, {Thomas B.} and J{\o}rgen Kjems and Henrik Hager",

year = "2020",

month = dec,

doi = "10.1038/s41467-020-18355-2",

language = "English",

volume = "11",

journal = "Nature Communications",

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Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory. / Kristensen, Lasse S.; Ebbesen, Karoline K.; Sokol, Martin et al.
In: Nature Communications, Vol. 11, 4551, 12.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory

AU - Kristensen, Lasse S.

AU - Ebbesen, Karoline K.

AU - Sokol, Martin

AU - Jakobsen, Theresa

AU - Korsgaard, Ulrik

AU - Eriksen, Ann C.

AU - Hansen, Thomas B.

AU - Kjems, Jørgen

AU - Hager, Henrik

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

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JO - Nature Communications

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

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