MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27 KIP1 axis

// Yangyang Wang 1, * , Jiping Zeng 2, * , Jianyong Pan 3 , Xue Geng 1 , Lupeng Li 2 , Jing Wu 1 , Ping Song 2 , Ying Wang 2 , Jilan Liu 2 , Lixiang Wang 1 1 Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, P.R.China 2 Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China 3 Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, P.R. China * These authors have contributed equally to this work Correspondence to: Lixiang Wang, email: wanglx@sdu.edu.cn Keywords: miR-320a, FoxM1, proliferation, gastric cancer, P27 KIP1 Received: December 06, 2015     Accepted: March 18, 2016     Published: April 11, 2016 ABSTRACT 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 P27 KIP1 , 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-P27 KIP1 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 P27 KIP1 expression in tumor tissues indicates that miR-320a suppression increases the tumor growth by enhancing FoxM1-P27 KIP1 signaling. These results thus reveal the crucial role played by miR-320a in limiting gastric carcinoma by directly targeting FoxM1- P27 KIP1 axis.