Praveen Sethupathy, PhD, an Assistant Professor in the Department of Genetics, was corresponding author of a study that investigated the role of microRNAs in the mediation of intestinal epithelial cell (IEC) homeostasis.
The paper titled “miR-30 Family Controls Proliferation and Differentiation of Intestinal Epithelial Cell Models by Directing a Broad Gene Expression Program that Includes SOX9 and the Ubiquitin Ligase Pathway” was published in the 29 July 2016 issue of JBC and featured the research of Bailey Peck, PhD, a former student in the Genetics and Molecular Biology Curriculum who recently defended her thesis and graduated. The study was founded on the hypothesis that miRNAs, in part through the regulation of SOX9, could mediate IEC homeostasis. Bioinformatic analysis of the SOX9 3’-UTR, revealed that the miR-30 family of miRNAs were highly expressed across various cell types of the mouse jejunal epithelium. Inhibiting miR-30 in human IECs and Caco-2 cells resulted in up-regulation of SOX9 mRNA but down-regulation of SOX9 protein. RNA sequencing was performed on the IEC cells and up-regulated genes were highly enriched for predicted miR-30 targets as well as genes in the ubiquitin-proteasome pathway. Inhibition of this pathway demonstrated that the regulation of SOX9 protein by miR-30 is largely indirect through the proteasome pathway. Inhibiting miR-30 family reduced IEC proliferation and increased markers of enterocyte differentiation, demonstrating that the miR-30 family likely plays a role in maintaining homeostasis in IECs. Link to the article: http://www.ncbi.nlm.nih.gov/pubmed/27261459