microRNA regulation of the expression of the estrogen receptor in endometrial cancer.

ABSTRACT

microRNAs (miRNAs) are non-coding RNA transcripts thought to be instrumental in controlling eukaryotic cell function. This study aimed to identify miRNAs associated with the differential expression of estrogen receptor α (ERα) and progesterone receptor (PR) in uterine endometrial cancer. First, the pathology of Ishikawa and KLE cell lines was identified by transplant and biopsy. Expression levels of ERα and PR and their response to estrogen and progesterone were examined, and total RNA was isolated to identify differentially expressed miRNAs by microarray analysis. miRNAs targeting ESR1 and PGR were predicted by miRANDA and TargetScan software, and their expression levels in cell lines and in patient samples were validated by real-time RT-PCR. Ishikawa and KLE represent estrogen-dependent and estrogen-independent endometrial cancers, respectively. As identified by miRNA microarray, 126 miRNAs were differentially expressed between the two cell lines; hsa-miR-100 and hsa-miR-99a were predicted to target ESR1, and hsa-miR-378 and hsa-miR-768-3p to target PGR. The differential expression of these miRNAs between Ishikawa and KLE was consistent in vivo and in vitro. Hsa-miR-100 was significantly down-regulated in the estrogen-dependent endometrial cancer samples as compared to the estrogen-independent samples and thus has the potential to target ESR1.