Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory
Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory
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DOI：
10.1038/s41467-020-18355-2
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发表时间：
2020-09-11
影响因子：
16.6
通讯作者：
Hager, Henrik
中科院分区：
文献类型：
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作者：
Kristensen, Lasse S.;Ebbesen, Karoline K.;Hager, Henrik
环状RNA（circRNA）最近在癌症研究领域获得了广泛关注，其中大多数环状RNA，包括假定的致癌基因ciRS-7（CDR1as），都被提议通过海绵特定的microRNA来发挥竞争性内源RNA（ceRNA）的作用。在这里，我们报告了结肠癌中 ciRS-7 的第一个空间分辨细胞表达模式，并表明 ciRS-7 在癌细胞中完全不存在，但在肿瘤微环境内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）可以通过所研究的肿瘤样本中不同的癌症与基质细胞比率来解释。总之，这些结果对未来的 circRNA 研究具有广泛的影响，并强调了拟用作 ceRNA 的 circRNA 空间解析表达模式的重要性。
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.