Assessing the ceRNA Hypothesis with Quantitative Measurements of miRNA and Target Abundance

Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the...

詳細記述

書誌詳細
主要な著者: Denzler, Rémy, Stefano, Joanna, Stoffel, Markus, Agarwal, Vikram, Bartel, David
その他の著者: Massachusetts Institute of Technology. Computational and Systems Biology Program
フォーマット: 論文
出版事項: Elsevier BV 2018
オンライン・アクセス:http://hdl.handle.net/1721.1/116326
https://orcid.org/0000-0001-8148-952X
https://orcid.org/0000-0002-3872-2856
その他の書誌記述
要約:Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target site abundance through expression of an miR-122 target in hepatocytes and livers and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target site abundance (≥1.5× 10 5 added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect.