MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer

Kohei Taniguchi; Nobuhiko Sugito; Minami Kumazaki; Haruka Shinohara; Nami Yamada; Yoshihito Nakagawa; Yuko Ito; Yoshinori Otsuki; Bunji Uno; Kazuhisa Uchiyama; Yukihiro Akao

doi:10.1016/j.canlet.2015.03.026

MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer

Kohei Taniguchi, Nobuhiko Sugito, Minami Kumazaki, Haruka Shinohara, Nami Yamada, Yoshihito Nakagawa, Yuko Ito, Yoshinori Otsuki, Bunji Uno, Kazuhisa Uchiyama, Yukihiro Akao

Gastroenterology

Research output: Contribution to journal › Article › peer-review

146 Citations (Scopus)

Abstract

Altered levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.8%) and CRC (57.6%) in 55 clinical samples. The ectopic expression of miR-124 induced apoptosis and autophagy in colon cancer cells. Also, miR-124 targeted polypyrimidine tract-binding protein 1 (. PTB1), which is a splicer of pyruvate kinase muscles 1 and 2 (. PKM1 and PKM2) and induced the switching of PKM isoform expression from PKM2 to PKM1. Also, siR-PTB1 induced drastic apoptosis in colon cancer cells. Furthermore, we found that the ectopic expression of miR-124 enhanced oxidative stress and the miR-124/PTB1/PKM1/PKM2 axis constituted a feedback cascade. Finally, we showed that intratumor injection of miR-124 and siR-PTB1 induced a tumor-suppressive effect in xenografted mice. The axis was established by both in vitro and in vivo experiments to function in human colorectal cancer cells. These findings suggest that miR-124 acts as a tumor-suppressor and a modulator of energy metabolism through a PTB1/PKM1/PKM2 feedback cascade in human colorectal tumor cells.

Original language	English
Pages (from-to)	17-27
Number of pages	11
Journal	Cancer Letters
Volume	363
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2015.03.026
Publication status	Published - 10-07-2015

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2015.03.026

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@article{9d5d5440026f41bcab21490aa6bf360b,

title = "MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer",

abstract = "Altered levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.8%) and CRC (57.6%) in 55 clinical samples. The ectopic expression of miR-124 induced apoptosis and autophagy in colon cancer cells. Also, miR-124 targeted polypyrimidine tract-binding protein 1 (. PTB1), which is a splicer of pyruvate kinase muscles 1 and 2 (. PKM1 and PKM2) and induced the switching of PKM isoform expression from PKM2 to PKM1. Also, siR-PTB1 induced drastic apoptosis in colon cancer cells. Furthermore, we found that the ectopic expression of miR-124 enhanced oxidative stress and the miR-124/PTB1/PKM1/PKM2 axis constituted a feedback cascade. Finally, we showed that intratumor injection of miR-124 and siR-PTB1 induced a tumor-suppressive effect in xenografted mice. The axis was established by both in vitro and in vivo experiments to function in human colorectal cancer cells. These findings suggest that miR-124 acts as a tumor-suppressor and a modulator of energy metabolism through a PTB1/PKM1/PKM2 feedback cascade in human colorectal tumor cells.",

keywords = "Colorectal cancer, MiR-124, PKM, PTB1, Warburg effect",

author = "Kohei Taniguchi and Nobuhiko Sugito and Minami Kumazaki and Haruka Shinohara and Nami Yamada and Yoshihito Nakagawa and Yuko Ito and Yoshinori Otsuki and Bunji Uno and Kazuhisa Uchiyama and Yukihiro Akao",

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doi = "10.1016/j.canlet.2015.03.026",

language = "English",

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T1 - MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer

AU - Taniguchi, Kohei

AU - Sugito, Nobuhiko

AU - Kumazaki, Minami

AU - Shinohara, Haruka

AU - Yamada, Nami

AU - Nakagawa, Yoshihito

AU - Ito, Yuko

AU - Otsuki, Yoshinori

AU - Uno, Bunji

AU - Uchiyama, Kazuhisa

AU - Akao, Yukihiro

PY - 2015/7/10

Y1 - 2015/7/10

N2 - Altered levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.8%) and CRC (57.6%) in 55 clinical samples. The ectopic expression of miR-124 induced apoptosis and autophagy in colon cancer cells. Also, miR-124 targeted polypyrimidine tract-binding protein 1 (. PTB1), which is a splicer of pyruvate kinase muscles 1 and 2 (. PKM1 and PKM2) and induced the switching of PKM isoform expression from PKM2 to PKM1. Also, siR-PTB1 induced drastic apoptosis in colon cancer cells. Furthermore, we found that the ectopic expression of miR-124 enhanced oxidative stress and the miR-124/PTB1/PKM1/PKM2 axis constituted a feedback cascade. Finally, we showed that intratumor injection of miR-124 and siR-PTB1 induced a tumor-suppressive effect in xenografted mice. The axis was established by both in vitro and in vivo experiments to function in human colorectal cancer cells. These findings suggest that miR-124 acts as a tumor-suppressor and a modulator of energy metabolism through a PTB1/PKM1/PKM2 feedback cascade in human colorectal tumor cells.

AB - Altered levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role of miR-124 in colorectal adenoma (CRA) and cancer (CRC). The expression levels of miR-124 were decreased in CRA (81.8%) and CRC (57.6%) in 55 clinical samples. The ectopic expression of miR-124 induced apoptosis and autophagy in colon cancer cells. Also, miR-124 targeted polypyrimidine tract-binding protein 1 (. PTB1), which is a splicer of pyruvate kinase muscles 1 and 2 (. PKM1 and PKM2) and induced the switching of PKM isoform expression from PKM2 to PKM1. Also, siR-PTB1 induced drastic apoptosis in colon cancer cells. Furthermore, we found that the ectopic expression of miR-124 enhanced oxidative stress and the miR-124/PTB1/PKM1/PKM2 axis constituted a feedback cascade. Finally, we showed that intratumor injection of miR-124 and siR-PTB1 induced a tumor-suppressive effect in xenografted mice. The axis was established by both in vitro and in vivo experiments to function in human colorectal cancer cells. These findings suggest that miR-124 acts as a tumor-suppressor and a modulator of energy metabolism through a PTB1/PKM1/PKM2 feedback cascade in human colorectal tumor cells.

KW - Colorectal cancer

KW - MiR-124

KW - PKM

KW - PTB1

KW - Warburg effect

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VL - 363

SP - 17

EP - 27

JO - Cancer Letters

JF - Cancer Letters

IS - 1

ER -

MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer

Abstract

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