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Title:
Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory | Nature Communications
Description:
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. The circular RNA named ciRS-7 is overexpressed in human cancers, however, its spatial cellular expression patterns have not been explored. Here, the authors show that ciRS-7 is not expressed in colon cancer cells, but abundant in stromal cells within tumours, and that cancer-to-stromal cell ratios contribute to correlations between ciRS-7 and miR-7 target genes.
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cancer, cirs, cells, expression, pubmed, rna, stromal, genes, google, scholar, target, cell, fig, colon, circular, correlations, cas, data, circrnas, samples, observed, expressed, tumor, central, nature, relative, found, supplementary, fos, analyses, sites, correlation, analysis, cellenriched, patients, rnas, positive, carcinoma, levels, mirna, nanostring, reporter, function, article, tissues, performed, ncounter, model, gene, putative,
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nature portfolio privacy policy hidden rna language pten/pi3k/akt signaling pathway regional ethical committee advertising watershed tools zymo research europe reprints nature 495 nature cancer development cancer research field enzyme-free digital counting phosphoinositide 3-kinase/akt pathway mir-7-seed fw/mir-7-seed ppc-dual color plasmid28 crispr/cas9 mediated removal author information authors future research crispr/cas9 mediated deletion paraffin-embedded cell pellets target-directed microrna degradation cancer cell-enriched genes upstream splice-acceptor site1 stromal cell-enriched genes nf-kappab signals nf-kappab signalling research design research council target-directed mirna degradation crispr/cas9 based strategy thermo fischer scientific thermo fisher scientific cognate mirna target genes small-cell lung cancer15 neural crest-derived melanocytes cancer cell-enriched circrnas cancer-initiating epithelial cells stromal cell-enriched circrnas xhoi/spei restriction sites pten signaling pathways classical oncogene-driven adenocarcinomas mirna-binding sites present small-cell lung cancer zz-pairs binding mir-7 permissions high-throughput rna sequencing 5-µm-thick paraffin sections circular rna cdr1as/cirs-7
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headline:Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory
description: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. The circular RNA named ciRS-7 is overexpressed in human cancers, however, its spatial cellular expression patterns have not been explored. Here, the authors show that ciRS-7 is not expressed in colon cancer cells, but abundant in stromal cells within tumours, and that cancer-to-stromal cell ratios contribute to correlations between ciRS-7 and miR-7 target genes.
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