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Helicobacter. 2014 Jun;19(3):174-81. doi: 10.1111/hel.12120. Epub 2014 Mar 17.

Helicobacter pylori modulates cisplatin sensitivity in gastric cancer by down-regulating miR-141 expression.

Author information

1
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.

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.

KEYWORDS:

Helicobacter pylori; cisplatin sensitivity; gastric cancer; miR-141

PMID:
24628843
DOI:
10.1111/hel.12120
[Indexed for MEDLINE]

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