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Significance Liver fibrosis interferes with normal organ function and supports tumor development in the liver. We uncovered a role of miRNAs in controlling liver fibrosis. In a comprehensive and systematic analysis we specify miRNA activities in targeting the fibrotic cellular microenvironment of the liver, in both mice and humans. We reveal and validate a complex network of 8 functionally connected miRNAs and 54 target genes to regulate structural, signaling, and remodeling components of the fibrotic extracellular matrix. We identify expression of this miRNA network to be controlled by the transcription factor Pparγ . Thus, we expand the antifibrotic function of Pparγ to controlling the synthesis of an antifibrotic miRNA network. This network may serve as a therapeutic target in antifibrotic therapies.

Identification of Ppar γ -modulated miRNA hubs that target the fibrotic tumor microenvironment