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

Nat Commun. 2020 Sep 11;11(1):4551. doi: 10.1038/s41467-020-18355-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oncogenes / genetics
  • Prospective Studies
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Spatial Analysis
  • Tumor Microenvironment / genetics*

Substances

  • MIRN7 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • long non-coding RNA CDR1AS, human