title: MiR-133b inhibits growth of human gastric cancer cells by silencing pyruvate kinase muscle-splicer polypyrimidine tract-binding protein 1.
abstract: The metabolism in tumor cells shifts from oxidative phosphorylation to glycolysis even in an aerobic environment. This phenomenon is known as the Warburg effect. This effect is regulated mainly by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the mRNA for the rate-limiting enzymes of glycolysis, pyruvate kinase muscle 1 and 2 (PKM1 and PKM2). In the present study, we demonstrated that miR-133b reduced PTBP1 expression at translational level and that the expression levels of miR-133b were significantly downregulated in gastric cancer clinical samples and human cell lines, whereas the protein expression level of PTBP1 was upregulated in 80% of the 20 clinical samples of gastric cancer examined. Ectopic expression of miR-133b and knockdown of PTBP1 in gastric cancer cells inhibited cell proliferation through the induction of autophagy by the switching of PKM isoform expression from PKM2-dominant to PKM1-dominant. The growth inhibition was partially canceled by an autophagy inhibitor 3-MA or a reactive oxygen species scavenger N-acetylcysteine. These findings indicated that miR-133b acted as a tumor-suppressor through negative regulation of the Warburg effect in gastric cancer cells.
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Matsuhashi
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajirika
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Futamura
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Takai
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.affiliation: Department of Surgical Oncology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D000066630:Ectopic Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008954:Models, Biological; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics*; D011770:Pyruvate Kinase / Q000235:genetics*; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; C450006:PTBP1 protein, human; D038941:Polypyrimidine Tract-Binding Protein; D011770:Pyruvate Kinase
keywords: Gastric cancer; MiR-133b; PTBP1; Warburg effect; pyruvate kinase