MicroRNA signaling in stem‐like ABCG2+ retinoblastoma cells

MicroRNAs are small noncoding RNAs that play an important role in posttranscriptional regulation of target genes, and control cancer initiation and development. Cancer stem cells are thought to possess the capacity of self‐renewal and differentiation to cause heterogeneous lineages of cancer cells. Recent studies have shown that miR‐328 and miR‐519c could target ABCG2 in breast and colon cancer cell lines, which is a hematopoietic progenitor on the cancer stem cell membrane. In this study, we investigated whether miRNAs related to ABCG2 regulation are differentially expressed in stem‐like cancer cells. RB143 human retinoblastoma cells were separated into stem‐like (ABCG2+) and non‐stem‐like (ABCG2−) populations through immunomagnetic selection. Real time quantitative PCR assays were used to determine the expression of miRNAs, as well as ABC transporters (MDR1/ABCB1, MRP1/ABCC1 and BCRP/ABCG2). ABCG2 was ~70‐fold higher in ABCG2+ cells, whereas there was no difference in ABCB1 expression between ABCG2− and ABCG2+ cells, and ABCC1 was undetectable. Very interestingly, miR‐328 was ~31‐fold lower and miR‐519c was ~34‐fold lower in ABCG2+ cells. In summary, ABCG2+ enriched cells exhibit remarkable difference in miRNA signaling from their ABCG2− counterparts. Additional studies on functionally relevant miRNAs may lead to new