Helicobacter pyloriModulates Cisplatin Sensitivity in Gastric Cancer by Down-Regulating miR-141 Expression

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Abstract

Background

Recent studies found that gastric cancer patients with Helicobacter pylori infection had a better response to chemotherapy and had an improved overall prognosis compared with those without. However, the underlying mechanism remains unknown.

Methods

Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression profile of miR-141 in H. pylori infected cells and tissues and their respective controls. qRT-PCR and Western blot were used to determine the expression level of KEAP-1. Luciferase reporter assays were used to determine whether KEAP-1 was a direct target of miR-141 in the gastric cancer cells. MTT and apoptosis assay were performed to detect the survival of cells under cisplatin treatment.

Result

We found that H. pylori infection can significantly down-regulate miR-141 expression. Knockdown miR-141 expression in 7901/DDP and 7901 cells could significantly improve cisplatin sensitivity. Over-expression of miR-141 resulted in enhanced resistance to cisplatin in both gastric cancer cells. We also demonstrated that miR-141 directly targets KEAP1 by luciferase reporter assay, and that down-regulation of KEAP1 induces cisplatin resistance. Conversely, over-expression of KEAP1 significantly enhanced cisplatin sensitivity. Our 75 pairs of tissues also showed that KEAP1 was significantly up-regulated in H. pylori-positive tissues.

Conclusion

Altogether, these findings demonstrated that the H. pylori infection could modulate cisplatin sensitivity through miR-141-mediated regulation of KEAP1.

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