Identification of MicroRNAs Involved in Resistance to Sunitinib in Renal Cell Carcinoma Cells.

Abstract

To generate sunitinib-resistant renal cell carcinoma (RCC) cell lines and identify miRNAs contributing to sunitinib resistance. Two RCC cell lines, ACHN and RCC23, were cultured by continuous treatment with sunitinib for 3 months, with doses gradually increasing up to the 50% inhibitory concentration for each cell line. We performed microarray and quantitative real-time polymerase chain reaction analyses of sunitinib-resistant ACHN (SR-ACHN) and RCC23 (SR-RCC23) cells, as well of as sunitinib-sensitive ACHN and RCC23 cells. SR-ACHN and SR-RCC23 cells exhibited significantly higher resistance to sunitinib treatment compared to sunitinib-sensitive cells. SR-ACHN and SR-RCC23 cells were hypertrophic and contained granules in the cytoplasm. When SR-ACHN and SR-RCC23 cells were compared to ACHN and RCC23 cells, expression of miR-575, miR-642b-3p, and miR-4430 was significantly increased, while that of miR-18a-5p, miR-29b-1-5p, miR-431-3p, and miR-4521 was significantly decreased. These miRNAs may contribute to sunitinib resistance in humans.