Identifying specific miRNAs and associated mRNAs in CD44 and CD90 cancer stem cell subtypes in gastric cancer cell line SNU-5.

Cancer stem cells (CSCs) are capable of generating multiple types of cells and play a vital role in promoting gastric cancer (GC) progression. Our previous research indicated that gastric CSCs with surface markers of CD44+ were more invasive compared to CD44- CD90+ CSCs (CD90+ CSCs), whereas CD90+ CSCs exhibited higher levels of proliferation than CD44+ CSCs. However, the mechanism and characteristics of marker-positive gastric CSCs are poorly understood. In this study, we profiled expression of miRNAs and mRNAs in CD44+ CSCs, CD90+ CSCs, and CD44- CD90- cell subtype (control) from SNU-5 cells by microarray analysis. Our results suggested some specially expressed miRNA-mRNA pairs in CD44+ and CD90+ CSCs. We performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to analyze the correlation and function of those pairs. We also validated the pairs that may play roles in metastasis by qRT-PCR. In CD44+ CSCs, we observed hsa-miR-15b-5p was up-regulated and its target genes AMOT, USP31, KALRN, EPB41L4B, ATP2B2, and EMC4 were down-regulated, which may relate to invasion and migration. In CD90+ CSCs, we observed hsa-miR-3631-3p is up-regulated, while its target genes QKI, TRIM67 and HMGA2 are down-regulated, which is associated with proliferation. We also found that hsa-miR-1910-5p is up-regulated while its target gene QKI and HMGA2 are down-regulated in CD90+ CSCs. The screened miRNA-mRNA pairs give us new insight into the mechanism of different phenotypes and biomarkers capable of identifying and isolating metastatic and tumorigenic CSCs. Those miRNA-mRNA pairs may also act as treatment for GC.