title: 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.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, P.R.China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250012, P.R. China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, P.R.China.
authors.forename: Xue
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China.
authors.forename: Lupeng
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, P.R.China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan 250012, P.R. China.
authors.forename: Jilan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan 250012, P.R.China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis* / Q000235:genetics; D000072278:Forkhead Box Protein M1 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C436291:CDKN1B protein, human; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: FoxM1; P27KIP1; gastric cancer; miR-320a; proliferation