MiR-320a inhibits gastric carcinoma by targeting activity in the FoxM1-P27KIP1 axis.

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 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.

• Authors: Yangyang Wang, Jiping Zeng, Jianyong Pan, Xue Geng, Lupeng Li, Jing Wu, Ping Song, Ying Wang, Jilan Liu, Lixiang Wang
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 20 Pg. 29275-86 (May 17 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27086911 (Publication Type: Journal Article)

Chemical References

• CDKN1B protein, human
• FOXM1 protein, human
• Forkhead Box Protein M1
• MIRN320 microRNA, human
• MicroRNAs
• Cyclin-Dependent Kinase Inhibitor p27

Topics

• Adenocarcinoma (genetics, pathology)
• Animals
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p27 (biosynthesis, genetics)
• Forkhead Box Protein M1 (biosynthesis, genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Heterografts
• Humans
• Mice
• Mice, Nude
• MicroRNAs (genetics)
• Stomach Neoplasms (genetics, pathology)