Effects of miR-222 on cisplatin resistance of renal cancer cell strains and related mechanisms

Abstract

Cisplatin is widely employed in combating renal cancers. However, a major challenge is the resistance of cisplatin by renal cancer cells. Increased miR-222 expression is known to promote this resistance and so ways of downregulating the expression of miR-222 is widely sought after as a means of combating the resistance. The study was performed to explore the effects of miR-222 on cisplatin resistance of renal cancer cell strains and related mechanisms. The expression of miR-222 and Dickkopf-3 (DKK3) was regulated to explore the effects of miR-222 and DKK3 on cisplatin chemotherapy in renal cancer cisplatin-resistant cell strains, and to figure out the regulatory relationship between miR-222 and DKK3. In renal cancer tissues and cell lines, miR-222 was highly expressed and DKK3 was lowly expressed. Renal cancer cisplatin-resistant cells had markedly higher miR-222 expression and lower DKK3 expression than normal renal cancer cells, suggesting a potential involvement of miR-222 and DKK3 in the cisplatin resistance in renal cancer cells. Down-regulated miR-222 expression led to stronger inhibition of the renal cancer cell growth by cisplatin and markedly higher DKK3 expression. Dual-luciferase reporter assay results showed that miR-222 had a targeted inhibition on DKK3. Co-transfection of miR-222 mimic and shDKK3, together with the up-regulation of miR-222 and DKK3 expressions, resulted in a higher sensitivity of renal cancer cells to cisplatin chemotherapy than the up-regulation of miR-222 expression alone. Down-regulated miR-222 expression can remove the inhibition of DKK3 expression and increase the sensitivity of renal cancer cells to cisplatin chemotherapy.