Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms

Kohei Taniguchi, Yuko Ito, Nobuhiko Sugito, Minami Kumazaki, Haruka Shinohara, Nami Yamada, Yoshihito Nakagawa, Tarou Sugiyama, Manabu Futamura, Yoshinori Otsuki, Kazuhiro Yoshida, Kazuhisa Uchiyama, Yukihiro Akao

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Article number8647
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015

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Polypyrimidine Tract-Binding Protein
Pyruvate Kinase
MicroRNAs
Protein Isoforms
Muscles
Neoplasms
Colon
Down-Regulation
Brain
Enzymes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Taniguchi, K., Ito, Y., Sugito, N., Kumazaki, M., Shinohara, H., Yamada, N., ... Akao, Y. (2015). Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms. Scientific reports, 5, [8647]. https://doi.org/10.1038/srep08647
Taniguchi, Kohei ; Ito, Yuko ; Sugito, Nobuhiko ; Kumazaki, Minami ; Shinohara, Haruka ; Yamada, Nami ; Nakagawa, Yoshihito ; Sugiyama, Tarou ; Futamura, Manabu ; Otsuki, Yoshinori ; Yoshida, Kazuhiro ; Uchiyama, Kazuhisa ; Akao, Yukihiro. / Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms. In: Scientific reports. 2015 ; Vol. 5.
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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.",
author = "Kohei Taniguchi and Yuko Ito and Nobuhiko Sugito and Minami Kumazaki and Haruka Shinohara and Nami Yamada and Yoshihito Nakagawa and Tarou Sugiyama and Manabu Futamura and Yoshinori Otsuki and Kazuhiro Yoshida and Kazuhisa Uchiyama and Yukihiro Akao",
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Taniguchi, K, Ito, Y, Sugito, N, Kumazaki, M, Shinohara, H, Yamada, N, Nakagawa, Y, Sugiyama, T, Futamura, M, Otsuki, Y, Yoshida, K, Uchiyama, K & Akao, Y 2015, 'Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms', Scientific reports, vol. 5, 8647. https://doi.org/10.1038/srep08647

Organ-specific PTB1-associated microRNAs determine expression of pyruvate kinase isoforms. / Taniguchi, Kohei; Ito, Yuko; Sugito, Nobuhiko; Kumazaki, Minami; Shinohara, Haruka; Yamada, Nami; Nakagawa, Yoshihito; Sugiyama, Tarou; Futamura, Manabu; Otsuki, Yoshinori; Yoshida, Kazuhiro; Uchiyama, Kazuhisa; Akao, Yukihiro.

In: Scientific reports, Vol. 5, 8647, 2015.

Research output: Contribution to journalArticle

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AU - Taniguchi, Kohei

AU - Ito, Yuko

AU - Sugito, Nobuhiko

AU - Kumazaki, Minami

AU - Shinohara, Haruka

AU - Yamada, Nami

AU - Nakagawa, Yoshihito

AU - Sugiyama, Tarou

AU - Futamura, Manabu

AU - Otsuki, Yoshinori

AU - Yoshida, Kazuhiro

AU - Uchiyama, Kazuhisa

AU - Akao, Yukihiro

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

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