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MicroRNAs mediate liver transcriptome changes upon soy diet intervention in mice

ABSTRACT: Soy-based diets have triggered the interest of the research community due to their beneficial effects on a wide variety of pathologies like breast and prostate cancer, diabetes, and atherosclerosis. However, the molecular details underlying these effects are far from being completely understood and several recent attempts have been made to elucidate the soy-induced liver transcriptome changes in different animal models. Here we used Next Generation Sequencing to identify a set of two microRNAs specifically modulated by short-term soy-enriched diet in young male mice and estimate their impact on the liver transcriptome assessed by microarray. Clustering and topological community detection (CTCD) network analysis of STRING generated interactions of transcriptome data led to the identification of five topological communities of genes characteristically altered and putatively targeted by microRNAs upon soy diet intervention.

ORGANISM(S): Mus musculus

PROVIDER: GSE111804 | GEO | 2018/03/15

REPOSITORIES: GEO

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Project description:The role of diet in the prevention of breast cancer is widely accepted, yet little is known on how early dietary effects mitigate adult cancer risk. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (GEN). We previously showed lower chemically-induced mammary tumor incidence in young adult rats with lifetime dietary intake of soy protein isolate (SPI), a highly refined soy product in infant formula, than in those fed the control diet Casein (CAS). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed CAS, SPI, or supplemental GEN-based diets. We identified mammary epithelial genes regulated by SPI (79 total) and GEN (99 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally cluster in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or GEN using QPCR. Wnt pathway inhibition by GEN was supported by lower Cyclin D1 immunoreactivity in mammary ductal epithelium of GEN relative to CAS and SPI, despite their comparable levels of membrane-localized E-cadherin and Î²-catenin. Identification of distinct GEN and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer. Experiment Overall Design: Female Sprague-Dawley rats, fed one of the three purified diets, were studied at postnatal day50. Total RNA( each RNA samples were extracted from #4 mammary gland from two animals under the same diet group) purified from non-tumor tissue within the proximal half of each colon, was used to prepare biotinylated probes, which were hybridized to Affymetrix RAE230 rat microarrays.

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MicroRNAs mediate liver transcriptome changes upon soy diet intervention in mice

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