Genomic analysis of nuclear receptors and miRNAs identifies a role for the NR3C1/miR-200 axis in colon cancer

Abstract

Background Nuclear receptors (NRs) are crucial transcription factors involved in cell proliferation, metabolism and homeostasis. Through the development of novel genomic approaches, unknown NR functions have recently been uncovered. NR networks derived from gene expression profiles revealed that NRs are tightly linked to human disease and that targeting these links could provide new therapeutic options. MicroRNAs (miRNAs) have known functions as transcriptional regulators of NR function. Objective I attempted to construct an NR-miRNA transcriptional network based on genomic data from human cancer. Methods I performed comprehensive analysis with genomic data. Correlation, clustering and survival analysis were done to identify the NR and miRNA correlation in cancer. Results Correlation analysis of genomic data revealed relationships between the expression levels of several NRs and miRNAs in human cancer. Based on my NR-miRNA correlation data, I found that NR3C1 expression was highly correlated with that of miR-200 in colon cancer. In most cases, miRNAs suppress expression of their target genes. Thus, miRNAs function as negative regulators during transcription. My analysis revealed that the miR-200 expression level is negatively correlated with that of NR3C1, demonstrating that miR-200 is a negative regulator of NR3C1 in colon cancer. It is known that miR-200 is a master regulator of EMT and that NR3C1 has a link with an EMT marker. Conclusions Overall, my genomic analysis revealed that the NR3C1 expression level is correlated with that of miR-200 and that this functional relationship might contribute to colon cancer cell survival. Modulating this axis could be a promising target for treating colon cancer patients. Graphic abstract