Diminution of miR-340-5p levels is responsible for increased expression of ABCB5 in melanoma cells under oxygen-deprived conditions

Abstract

Melanoma is usually highly refractory to chemotherapy. This resistance to treatment is mainly due to high heterogeneity and plasticity of melanoma cells strictly connected to changes in tumor microenvironment. Hypoxia can drastically alter cancer biology. Solid tumor cells under hypoxia gain stem-like features, they are more invasive and drug-resistant than their normoxic counterparts. These effects could be mediated by changes in miRNA expression under hypoxia. MiRNAs are small non-coding RNA molecules that can negatively control gene expression. In the present study using microarray technology we evaluated the expression of miRNAs in melanoma cells derived from nodular melanoma and grown under normoxic and hypoxic conditions. Using R environment for statistical analysis we found that 70 miRNAs were differentially-expressed, and 16 of them were significantly down-regulated in melanoma cells grown in hypoxic conditions compared to cells grown in normoxia. We intended to find transcripts whose expression is increased due to down-regulation of selected miRNAs. Bioinformatics analysis revealed that increased levels of HIF-2α, ABCB5, OCT4, SOX2 and ZEB1 in different melanoma populations under hypoxia could be a result of significant down-regulation of miR-340-5p. Inhibition of miR-340-5p confirmed that this miRNA negatively influences the expression of ABCB5. This is the first study showing the relationship between miR-340-5p and expression of ABCB5, a transmembrane transporter involved in drug resistance considered as a marker of melanoma stem-like cells.