title: Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms.
abstract: The Warburg effect is a well-known feature of cancer cells. However, its' functional significance hasn't been elucidated yet. Pyruvate kinase muscle (PKM), which is a rate-limiting glycolytic enzyme, has 2 isoforms, PKM1 and PKM2. It has been reported that PKM2 is a tumor-specific isoform and promotes the Warburg effect. Also, it has been thought that tumor cells switch their PKM isoform from PKM1 to PKM2 during tumor development. Here, we showed that this switching machinery was induced only in limited cases, based on PKM expression in normal tissues, and that brain-specific microRNA (miR)-124 and muscle-specific miR-133b regulated this machinery by controlling PKM expression through targeting polypyrimidine tract-binding protein 1 (PTB1), which is a splicer of the PKM gene. Also, we confirmed that the PKM2/PKM1 ratio was further elevated in other PKM2-dominant organs such as colon through the down-regulation of these PTB1-associated microRNAs during tumor development.
authors.affiliation: 1] United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan [2] Department of General and Gastroenterological Surgery, Osaka Medical College, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Taniguchi
authors.affiliation: Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ito
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Sugito
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kumazaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Shinohara
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology, Fujita Health University, School of Medicine, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Oncological surgery, Gifu University School of medicine, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Tarou
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Oncological surgery, Gifu University School of medicine, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Futamura
authors.affiliation: Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otsuki
authors.affiliation: Department of Oncological surgery, Gifu University School of medicine, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of General and Gastroenterological Surgery, Osaka Medical College, Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Uchiyama
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008954:Models, Biological; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009928:Organ Specificity; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007527:Isoenzymes; D008565:Membrane Proteins; D035683:MicroRNAs; D038941:Polypyrimidine Tract-Binding Protein; D011770:Pyruvate Kinase; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C509207:MIRN124 microRNA, human; C548234:MIRN133 microRNA, human; C450006:PTBP1 protein, human