MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27KIP1 axis
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Yangyang Wang1,*, Jiping Zeng2,*, Jianyong Pan3, Xue Geng1, Lupeng Li2, Jing Wu1, Ping Song2, Ying Wang2, Jilan Liu2, Lixiang Wang1
1Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, P.R.China
2Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China
3Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, P.R. China
*These authors have contributed equally to this work
Lixiang Wang, email: email@example.com
Keywords: miR-320a, FoxM1, proliferation, gastric cancer, P27KIP1
Received: December 06, 2015 Accepted: March 18, 2016 Published: April 11, 2016
MicroRNAs (miRNAs) regulate tumorigenesis by inhibiting gene expression. In this study, we showed that miR-320a expression is decreased in human gastric cancer tissues and correlates inversely with expression of FoxM1, a key cell cycle regulator involved in gastric carcinoma. By contrast, the expression of P27KIP1, a downstream effector of FoxM1, correlates positively with miR-320a levels. Luciferase assays indicate that miR-320a suppresses FoxM1 expression, and in vitro recovery tests using FoxM1 siRNA indicate miR-320a inhibits gastric cancer cell proliferation by suppressing activity in the FoxM1-P27KIP1 axis. In vivo, nude mice injected with BGC-823 gastric cancer cells expressing a miR-320a inhibitor exhibit faster tumor growth than mice injected with control cells. Analysis of FoxM1 and P27KIP1 expression in tumor tissues indicates that miR-320a suppression increases the tumor growth by enhancing FoxM1-P27KIP1 signaling. These results thus reveal the crucial role played by miR-320a in limiting gastric carcinoma by directly targeting FoxM1- P27KIP1 axis.
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