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

Author

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  • Lasse S. Kristensen

    (Aarhus University
    Interdisciplinary Nanoscience Center (iNANO), Aarhus University
    Aarhus University)

  • Karoline K. Ebbesen

    (Aarhus University
    Interdisciplinary Nanoscience Center (iNANO), Aarhus University)

  • Martin Sokol

    (Vejle Hospital)

  • Theresa Jakobsen

    (Aarhus University)

  • Ulrik Korsgaard

    (Vejle Hospital)

  • Ann C. Eriksen

    (Vejle Hospital)

  • Thomas B. Hansen

    (Aarhus University
    Interdisciplinary Nanoscience Center (iNANO), Aarhus University)

  • Jørgen Kjems

    (Aarhus University
    Interdisciplinary Nanoscience Center (iNANO), Aarhus University)

  • Henrik Hager

    (Vejle Hospital
    Danish Colorectal Cancer Center South, Vejle Hospital)

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.

Suggested Citation

  • Lasse S. Kristensen & Karoline K. Ebbesen & Martin Sokol & Theresa Jakobsen & Ulrik Korsgaard & Ann C. Eriksen & Thomas B. Hansen & Jørgen Kjems & Henrik Hager, 2020. "Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18355-2
    DOI: 10.1038/s41467-020-18355-2
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    Cited by:

    1. Wanying Wu & Jinyang Zhang & Xiaofei Cao & Zhengyi Cai & Fangqing Zhao, 2022. "Exploring the cellular landscape of circular RNAs using full-length single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Peng Wang & Zhitao Huang & Yili Peng & Hongwei Li & Tong Lin & Yingyu Zhao & Zheng Hu & Zhanmei Zhou & Weijie Zhou & Youhua Liu & Fan Fan Hou, 2022. "Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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