Regulatory interaction of HNF1-alpha to microRNA-194 gene during intestinal epithelial cell differentiation

Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Bunkyoku, Tokyo, Japan.
Nucleic Acids Symposium Series 02/2007; 51(51):415-6. DOI: 10.1093/nass/nrm208
Source: PubMed


Maintenance of intestinal epithelium is based on well-balanced molecular mechanisms that confer the stable and continuous supply of specialized epithelial cell lineages from multipotent progenitors. Lineage commitment decisions in intestinal epithelium system involve multiple regulatory systems that interplay each other to establish the cellular identities. Here, we demonstrate that the microRNA system could be involved in intestinal epithelial cell differentiation and that microRNA-194 (miR194) is highly induced during this process and controlled by a transcription factor, HNF-alpha, that is well known to regulate gene expression in intestinal epithelial cells. Thus, the 5' conserved genomic region of miR-1942 gene, the inducible class of miR-194 parental gene, contains a binding motif for HNF1-alpha. This consensus region is required for the transcription of miR-1942 and active in intestinal epithelial cell line, Caco-2, in-vivo. Our observations indicate that microRNA genes could be targets of lineage specific transcription factors and that microRNAs are regulated in intestinal epithelial cells in a tissue specific manner. Given that role of microRNA in fine tuning of gene expression patterns, our results suggest that HNF1-alpha regulates the gene expression program by not only direct activation of genes but also modulation through induction of microRNAs such as miR-194, in intestinal epithelial cells. This represents a novel molecular machinery that might specify the fates of intestinal epithelial cell lineages during their differentiation.

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    • "High levels of miR-194 are expressed in the intestines and liver [50], [51]. Hepatocyte nuclear factor (HNF) can induce miR-194 expression during intestinal epithelial cell differentiation [52], [53]. miR-194 suppresses invasion and migration of liver mesenchymal-like cancer cells [54]. "
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    • "(Supplementary Table S1). We confirmed high-level expression of previously known abundant microRNAs in the respective tissue, such as mir-122 and mir-192 in the liver, miR-215 and miR-192 in the intestine, and miR-375 and miR-152 in the pancreas (Supplementary Table S1) (16–20). The let-7 family was highly expressed in all tissues. "
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    • "There are some limited reports on intestinal epithelial miRNA expression. Takada et al. [27] showed high abundance of miR-143 and miR-194 in mouse small intestine and Hino et al. [16], [28] further showed induction of miR-194 by HNF-1 during differentiation of intestinal epithelial Caco-2 cells. We used a sensitive model for stimulating intestinal crypt cell proliferation by a growth factor, and obtained not only the first extensive mouse intestinal crypt cell miRNA profiles, but also the differentially expressed miRNA species during cell proliferation. "
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