Sex-biased mouse liver lincRNAs: validation and impact of mouse knockout models that perturb hepatic growth signaling
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Sexual dimorphism has a broad impact on human health and disease, including autoimmune diseases, cardiovascular diseases, and liver diseases, specifically hepatocellular carcinoma. Pituitary growth hormone (GH) secretion has a major impact on sex differences in the liver. Previous studies show that signal transducer and activator transcription factor 5b (STAT5b) impacts male-biased gene expression. Somatostatin (SST) inhibits the release of GH, and this in turn impacts STAT5b activity and GH regulation feedback. Long intergenic noncoding RNAs (lincRNAs), which do not encode proteins, have various roles in diverse biological processes including cell differentiation, chromatin remodeling, and gene regulation. In the present study, we discovered lincRNAs in mouse liver using RNA-seq datasets, and identified male and female-biased lincRNAs. Moreover, we validated the sex-specificity of lincRNAs by performing real time PCR (qPCR) and analyzing UCSC genome browser screen shots by comparing male and female expression patterns. We validated the sex-specificities of 22 lincRNAs. Moreover, we investigated whether pituitary GH secretion impacts the regulation of these sex-biased lincRNAs in the same manner as seen in sex-biased protein coding RefSeq genes. qPCR experiments investigated the impact of GH secretion by using SST and STAT5b knockout mouse models, and hypophysectomized, and intermittent (pulsatile) GH-treated mice. Our results show that pituitary GH secretion impacts the regulation of sex-biased lincRNAs. The last part of this thesis investigates the molecular and functional role of sexbiased lincRNAs by using The Database for Annotation, Visualization, and Integrated Discovery (DAVID).