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.

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miR-222对肾癌细胞株顺铂耐药性的影响及相关机制

顺铂广泛用于抗击肾癌。但是，主要的挑战是肾癌细胞对顺铂的耐药性。已知增加的miR-222表达可促进这种抗性，因此广泛寻求下调miR-222表达的方法作为抵抗抗性的手段。进行该研究以探索miR-222对肾癌细胞株的顺铂耐药性的影响及其相关机制。调节miR-222和Dickkopf-3（DKK3）的表达，以探讨miR-222和DKK3对肾癌顺铂耐药细胞株顺铂化疗的影响，并探讨miR-222和DKK3之间的调节关系。 。在肾癌组织和细胞系中，miR-222高表达而DKK3低表达。肾癌顺铂耐药细胞比正常肾癌细胞具有更高的miR-222表达和更低的DKK3表达，表明miR-222和DKK3可能参与了肾癌细胞的顺铂耐药。下调的miR-222表达导致顺铂对肾癌细胞生长的抑制作用更强，而DKK3表达则明显升高。双荧光素酶报告基因检测结果表明，miR-222对DKK3具有靶向抑制作用。miR-222模拟物和shDKK3的共转染，以及miR-222和DKK3表达的上调，导致肾癌细胞对顺铂化疗的敏感性高于仅miR-222表达的上调。