期刊
ONCOTARGET
卷 7, 期 20, 页码 29275-29286出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8676
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资金
- National Natural Science Foundation of China [81272654, 81172354, 81171536, 81371781]
- National Basic Research Program of China (973 Program) [2012CB911202]
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.
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