Lysosome-associated membrane protein 2 (LAMP-2) expression induced by miR-194-5p downregulation contributes to sunitinib resistance in human renal cell carcinoma cells.

Abstract

Sunitinib is a tyrosine kinase inhibitor that is used as the primary treatment in metastatic renal cell carcinoma (RCC). The main difficulty associated with its use is the development of drug resistance. In the present study, ACHN cells, a human renal cell carcinoma cell line, were used to establish sunitinib-resistant (SR) cells. Microarray analysis and reverse transcription-quantitative polymerase chain reaction revealed that miR-194-5p expression was significantly decreased in SR-ACHN cells when compared with that observed in ACHN cells (P<0.05). Transfection of miR-194-5p, though not with negative control miR, in SR-ACHN cells could significantly inhibit cell proliferation following sunitinib treatment (2.5–40 µM; P<0.05). Western blotting demonstrated that the expression of lysosome-associated membrane protein-2 (LAMP-2), which attenuates the anti-proliferative effect of sunitinib, was significantly higher in SR-ACHN than in ACHN cells (P<0.01). In addition, LAMP-2 expression was suppressed by miR-194-5p transfection in SR-ACHN cells. These data suggested that miR-194-5p downregulation may be associated with sunitinib resistance via the induction of LAMP-2 expression in human RCC.