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在癌症中对假定致癌基因 ciRS-7 的空间表达分析改变了 microRNA 海绵理论。

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

机构信息

Department of Molecular Biology and Genetics (MBG), Aarhus University, C.F. Møllers Allé 3, DK-8000, Aarhus, Denmark.

Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, DK-8000, Aarhus, Denmark.

出版信息

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

DOI:10.1038/s41467-020-18355-2
PMID:32917870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7486402/
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.

摘要

环状 RNA（circRNAs）在癌症研究领域引起了广泛关注，其中大多数，包括假定的癌基因 ciRS-7（CDR1as），被提议作为竞争性内源性 RNA（ceRNAs）通过海绵特定的 microRNA 发挥作用。在这里，我们报告了 ciRS-7 在结肠癌中的第一个空间分辨的细胞表达模式，并表明 ciRS-7 在癌细胞中完全缺失，但在肿瘤微环境中的基质细胞中高度表达。此外，我们的数据表明，这通常适用于经典的癌基因驱动的腺癌，但不适用于其他癌症，包括恶性黑色素瘤。此外，我们发现 circRNA 和 mRNA 表达之间的相关性，通常被解释为 ceRNA 功能的证据，可以通过研究肿瘤标本中不同的癌细胞与基质细胞比例来解释。总之，这些结果对未来的 circRNA 研究具有广泛的意义，并强调了空间解析拟作为 ceRNAs 发挥作用的 circRNA 表达模式的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/9ad16975d201/41467_2020_18355_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/701446e6266a/41467_2020_18355_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/611feec054d5/41467_2020_18355_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/52310c858465/41467_2020_18355_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/eaecd3d77ac6/41467_2020_18355_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/5ea279901b96/41467_2020_18355_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/9ad16975d201/41467_2020_18355_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/701446e6266a/41467_2020_18355_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/611feec054d5/41467_2020_18355_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/52310c858465/41467_2020_18355_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/eaecd3d77ac6/41467_2020_18355_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/5ea279901b96/41467_2020_18355_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa4e/7486402/9ad16975d201/41467_2020_18355_Fig6_HTML.jpg

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