PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors

Kohei Taniguchi, Miku Sakai, Nobuhiko Sugito, Minami Kumazaki, Haruka Shinohara, Nami Yamada, Tatsushi Nakayama, Hiroshi Ueda, Yoshihito Nakagawa, Yuko Ito, Manabu Futamura, Bunji Uno, Yoshinori Otsuki, Kazuhiro Yoshida, Kazuhisa Uchiyama, Yukihiro Akao

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

It is known that pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has essential roles in the Warburg effect and that expression of cancer-dominant PKM2 is increased by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the PKM gene. In other words, PKM2 acts as a promoter of the Warburg effect. Previously, we demonstrated that the Warburg effect was partially established by down-regulation of several microRNAs (miRs) that bind to PTBP1 and that ectopic expression of these miRs suppressed the Warburg effect. In this study, we investigated the functions of miR-1 and -133b, which are well known as muscle-specific miRs, from the viewpoint of the Warburg effect in colorectal tumors. The expression levels of miR-1 and -133b were relatively high in colon tissue except muscle and very frequently down-regulated in 75 clinical colorectal tumors samples, even in adenomas, compared with those of the adjacent normal tissue samples. The ectopic expression of these miRs induced growth suppression and autophagic cell death through the switching of PKM isoform expression from PKM2 to PKM1 by silencing PTBP1 expression both in vitro and in vivo. Also, we showed that the resultant increase in the intracellular level of reactive oxygen species (ROS) was involved in this mechanism. Furthermore, PTBP1 was highly expressed in most of the 30 clinical colorectal tumor samples examined, even in adenomas. Our results suggested that PTBP1 and PTBP1-associated miR-1 and -133b are crucial molecules for the maintenance of the Warburg effect in colorectal tumors.

Original languageEnglish
Pages (from-to)18940-18952
Number of pages13
JournalOncotarget
Volume7
Issue number14
DOIs
Publication statusPublished - 01-01-2016

Fingerprint

Polypyrimidine Tract-Binding Protein
MicroRNAs
Colorectal Neoplasms
Pyruvate Kinase
Muscles
Adenoma
Autophagy
Reactive Oxygen Species
Protein Isoforms
Colon
Down-Regulation
Maintenance
Enzymes
Growth

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Taniguchi, K., Sakai, M., Sugito, N., Kumazaki, M., Shinohara, H., Yamada, N., ... Akao, Y. (2016). PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. Oncotarget, 7(14), 18940-18952. https://doi.org/10.18632/oncotarget.8005
Taniguchi, Kohei ; Sakai, Miku ; Sugito, Nobuhiko ; Kumazaki, Minami ; Shinohara, Haruka ; Yamada, Nami ; Nakayama, Tatsushi ; Ueda, Hiroshi ; Nakagawa, Yoshihito ; Ito, Yuko ; Futamura, Manabu ; Uno, Bunji ; Otsuki, Yoshinori ; Yoshida, Kazuhiro ; Uchiyama, Kazuhisa ; Akao, Yukihiro. / PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. In: Oncotarget. 2016 ; Vol. 7, No. 14. pp. 18940-18952.
@article{f335b94a5afb48178a07b5518bd36d2d,
title = "PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors",
abstract = "It is known that pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has essential roles in the Warburg effect and that expression of cancer-dominant PKM2 is increased by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the PKM gene. In other words, PKM2 acts as a promoter of the Warburg effect. Previously, we demonstrated that the Warburg effect was partially established by down-regulation of several microRNAs (miRs) that bind to PTBP1 and that ectopic expression of these miRs suppressed the Warburg effect. In this study, we investigated the functions of miR-1 and -133b, which are well known as muscle-specific miRs, from the viewpoint of the Warburg effect in colorectal tumors. The expression levels of miR-1 and -133b were relatively high in colon tissue except muscle and very frequently down-regulated in 75 clinical colorectal tumors samples, even in adenomas, compared with those of the adjacent normal tissue samples. The ectopic expression of these miRs induced growth suppression and autophagic cell death through the switching of PKM isoform expression from PKM2 to PKM1 by silencing PTBP1 expression both in vitro and in vivo. Also, we showed that the resultant increase in the intracellular level of reactive oxygen species (ROS) was involved in this mechanism. Furthermore, PTBP1 was highly expressed in most of the 30 clinical colorectal tumor samples examined, even in adenomas. Our results suggested that PTBP1 and PTBP1-associated miR-1 and -133b are crucial molecules for the maintenance of the Warburg effect in colorectal tumors.",
author = "Kohei Taniguchi and Miku Sakai and Nobuhiko Sugito and Minami Kumazaki and Haruka Shinohara and Nami Yamada and Tatsushi Nakayama and Hiroshi Ueda and Yoshihito Nakagawa and Yuko Ito and Manabu Futamura and Bunji Uno and Yoshinori Otsuki and Kazuhiro Yoshida and Kazuhisa Uchiyama and Yukihiro Akao",
year = "2016",
month = "1",
day = "1",
doi = "10.18632/oncotarget.8005",
language = "English",
volume = "7",
pages = "18940--18952",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "14",

}

Taniguchi, K, Sakai, M, Sugito, N, Kumazaki, M, Shinohara, H, Yamada, N, Nakayama, T, Ueda, H, Nakagawa, Y, Ito, Y, Futamura, M, Uno, B, Otsuki, Y, Yoshida, K, Uchiyama, K & Akao, Y 2016, 'PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors', Oncotarget, vol. 7, no. 14, pp. 18940-18952. https://doi.org/10.18632/oncotarget.8005

PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. / Taniguchi, Kohei; Sakai, Miku; Sugito, Nobuhiko; Kumazaki, Minami; Shinohara, Haruka; Yamada, Nami; Nakayama, Tatsushi; Ueda, Hiroshi; Nakagawa, Yoshihito; Ito, Yuko; Futamura, Manabu; Uno, Bunji; Otsuki, Yoshinori; Yoshida, Kazuhiro; Uchiyama, Kazuhisa; Akao, Yukihiro.

In: Oncotarget, Vol. 7, No. 14, 01.01.2016, p. 18940-18952.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors

AU - Taniguchi, Kohei

AU - Sakai, Miku

AU - Sugito, Nobuhiko

AU - Kumazaki, Minami

AU - Shinohara, Haruka

AU - Yamada, Nami

AU - Nakayama, Tatsushi

AU - Ueda, Hiroshi

AU - Nakagawa, Yoshihito

AU - Ito, Yuko

AU - Futamura, Manabu

AU - Uno, Bunji

AU - Otsuki, Yoshinori

AU - Yoshida, Kazuhiro

AU - Uchiyama, Kazuhisa

AU - Akao, Yukihiro

PY - 2016/1/1

Y1 - 2016/1/1

N2 - It is known that pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has essential roles in the Warburg effect and that expression of cancer-dominant PKM2 is increased by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the PKM gene. In other words, PKM2 acts as a promoter of the Warburg effect. Previously, we demonstrated that the Warburg effect was partially established by down-regulation of several microRNAs (miRs) that bind to PTBP1 and that ectopic expression of these miRs suppressed the Warburg effect. In this study, we investigated the functions of miR-1 and -133b, which are well known as muscle-specific miRs, from the viewpoint of the Warburg effect in colorectal tumors. The expression levels of miR-1 and -133b were relatively high in colon tissue except muscle and very frequently down-regulated in 75 clinical colorectal tumors samples, even in adenomas, compared with those of the adjacent normal tissue samples. The ectopic expression of these miRs induced growth suppression and autophagic cell death through the switching of PKM isoform expression from PKM2 to PKM1 by silencing PTBP1 expression both in vitro and in vivo. Also, we showed that the resultant increase in the intracellular level of reactive oxygen species (ROS) was involved in this mechanism. Furthermore, PTBP1 was highly expressed in most of the 30 clinical colorectal tumor samples examined, even in adenomas. Our results suggested that PTBP1 and PTBP1-associated miR-1 and -133b are crucial molecules for the maintenance of the Warburg effect in colorectal tumors.

AB - It is known that pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has essential roles in the Warburg effect and that expression of cancer-dominant PKM2 is increased by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the PKM gene. In other words, PKM2 acts as a promoter of the Warburg effect. Previously, we demonstrated that the Warburg effect was partially established by down-regulation of several microRNAs (miRs) that bind to PTBP1 and that ectopic expression of these miRs suppressed the Warburg effect. In this study, we investigated the functions of miR-1 and -133b, which are well known as muscle-specific miRs, from the viewpoint of the Warburg effect in colorectal tumors. The expression levels of miR-1 and -133b were relatively high in colon tissue except muscle and very frequently down-regulated in 75 clinical colorectal tumors samples, even in adenomas, compared with those of the adjacent normal tissue samples. The ectopic expression of these miRs induced growth suppression and autophagic cell death through the switching of PKM isoform expression from PKM2 to PKM1 by silencing PTBP1 expression both in vitro and in vivo. Also, we showed that the resultant increase in the intracellular level of reactive oxygen species (ROS) was involved in this mechanism. Furthermore, PTBP1 was highly expressed in most of the 30 clinical colorectal tumor samples examined, even in adenomas. Our results suggested that PTBP1 and PTBP1-associated miR-1 and -133b are crucial molecules for the maintenance of the Warburg effect in colorectal tumors.

UR - http://www.scopus.com/inward/record.url?scp=84975522422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975522422&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.8005

DO - 10.18632/oncotarget.8005

M3 - Article

C2 - 26980745

AN - SCOPUS:84975522422

VL - 7

SP - 18940

EP - 18952

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 14

ER -

Taniguchi K, Sakai M, Sugito N, Kumazaki M, Shinohara H, Yamada N et al. PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. Oncotarget. 2016 Jan 1;7(14):18940-18952. https://doi.org/10.18632/oncotarget.8005