Characterization of microRNA expression profile in endometrial cancer stem cells during differentiation

Objective: To obtain comprehensive expression profile of microRNAs (miRNAs) in endometrial cancer stem cells (ECSCs) during differentiation. Methods: ECSCs were enriched by spheroid formation and spontaneously differentiated into cancer cells by attached culture. We characterized miRNA expression in ECSCs and its differentiated cells using miRNA microarrays and verified the results by RT-qPCR. Meanwhile, we applied bioinformatic method to predict the target genes of the differentially expressed miRNAs. Furthermore, gene expression profile was detected by genomic microarray. Finally, we summarized the relationship between the predicted target genes of miRNAs and gene expression profile. Results: We observed that 10 miRNAs were significantly upregulated in ECSCs, including miR-522, miR-139-3p, miR-520c-5p, miR-518d-5p, miR-146b-5p, miR-34a, miR-526a, miR-193a-3p, miR-221, and miR-4674. Only 1 miRNA, miR-760, was downregulated in ECSCs. A total of 11 differentially expressed miRNAs were identified by RT-qPCR. The results showed these differentially expressed miRNAs (except miR-526a and miR-4674) were in accordance with those obtained by miRNA microarray analysis. By using bioinformatic approach, the target genes of these differentially expressed miRNAs could be found. The results of genomic microarray showed that 207 genes were more highly expressed and 238 genes were more lowly expressed in ECSCs compared with its differentiated cells. Analysis of the gene expression profile and the predicted target genes of miRNAs showed that some common genes except miR-139-3p could be found. Conclusion: Our study provides an available information about miRNAs and target genes from different starting points, such as ECSCs differentiation. Further studies are needed to ascertain the role of these miRNAs in ECSCs' differentiation.