Mechanism of miRNA-451 Regulating Resistance of Gastric Cancer Cells to 5-Fu Through MRP

Objective To investigate the mechanism of miR-451 regulating the resistance of gastric cancer to 5-Fu by down-regulating the expression of MRP.

Methods Real-time quantitative PCR was used to detect the relative expression of miR-451 in 20 pairs of human gastric cancer tissues and adjacent tissues and gastric cancer cell lines. The expression of miR-451 in the resistance group and non-resistant group were detected. We constructed gastric cancer cell line with stable plent-miR-451 overexpression, and the overexpression efficiency of miR-451 in gastric cancer cell line was detected by real-time quantitative PCR. The proliferation activity of the cells was detected by CCK8. The miR-451 target gene was analyzed by bioinformatics method and verified by luciferase assay. The effect of miR-451 on the mRNA and protein of targeted gene MRP were detected by real-time quantitative PCR and Western blot.

Results The expression of miR-451 in normal tissues was higher than that in cancer tissues, and miR-451 expression in the non-resistant gastric cancer tissues was higher than that in the drug-resistant gastric cancer tissues. The overexpression of miR-451 reduced the resistance of gastric cancer cells to 5-Fu treatment (P=0.0006). Bioinformatics analysis showed that MRP was the target gene of miR-451. Luciferase assay also confirmed that MRP was a potential target gene of miR-451. miR-451 overexpression decreased the mRNA and protein of the drug resistance gene MRP (P=0.00069).

Conclusion Overexpression of miR451 could down-regulate MRP expression, which reduces the resistance of tumor cells to 5-Fu.