小RNA
生物
癌症研究
纤维化
肝细胞癌
细胞生物学
癌症
癌变
下调和上调
转录组
过氧化物酶体增殖物激活受体
表型
计算生物学
基因
医学
病理
遗传学
作者
Ivana Winkler,Catrin Bitter,Sebastian Winkler,Dieter Weichenhan,Abhishek Thavamani,Jan G. Hengstler,Erawan Borkham-Kamphorst,Oliver Kohlbacher,Christoph Plass,Robert Geffers,Ralf Weiskirchen,Alfred Nordheim
标识
DOI:10.1073/pnas.1909145117
摘要
Liver fibrosis interferes with normal liver function and facilitates hepatocellular carcinoma (HCC) development, representing a major threat to human health. Here, we present a comprehensive perspective of microRNA (miRNA) function on targeting the fibrotic microenvironment. Starting from a murine HCC model, we identify a miRNA network composed of 8 miRNA hubs and 54 target genes. We show that let-7, miR-30, miR-29c, miR-335, and miR-338 (collectively termed antifibrotic microRNAs [AF-miRNAs]) down-regulate key structural, signaling, and remodeling components of the extracellular matrix. During fibrogenic transition, these miRNAs are transcriptionally regulated by the transcription factor Ppar γ and thus we identify a role of Ppar γ as regulator of a functionally related class of AF-miRNAs. The miRNA network is active in human HCC, breast, and lung carcinomas, as well as in 2 independent mouse liver fibrosis models. Therefore, we identify a miRNA:mRNA network that contributes to formation of fibrosis in tumorous and nontumorous organs of mice and humans.
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