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

研究成果: Article

70 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)17-27
ページ数11
ジャーナルCancer Letters
363
発行部数1
DOI
出版物ステータスPublished - 10-07-2015

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MicroRNAs
Colorectal Neoplasms
Growth
Adenoma
Colonic Neoplasms
Neoplasms
Polypyrimidine Tract-Binding Protein
Apoptosis
Pyruvate Kinase
Autophagy
Energy Metabolism
Protein Isoforms
Carcinogenesis
Oxidative Stress
Muscles
Injections
Ectopic Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Taniguchi, Kohei ; Sugito, Nobuhiko ; Kumazaki, Minami ; Shinohara, Haruka ; Yamada, Nami ; Nakagawa, Yoshihito ; Ito, Yuko ; Otsuki, Yoshinori ; Uno, Bunji ; Uchiyama, Kazuhisa ; Akao, Yukihiro. / MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer. :: Cancer Letters. 2015 ; 巻 363, 番号 1. pp. 17-27.
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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.",
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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Taniguchi, K, Sugito, N, Kumazaki, M, Shinohara, H, Yamada, N, Nakagawa, Y, Ito, Y, Otsuki, Y, Uno, B, Uchiyama, K & Akao, Y 2015, 'MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer', Cancer Letters, 巻. 363, 番号 1, pp. 17-27. https://doi.org/10.1016/j.canlet.2015.03.026

MicroRNA-124 inhibits cancer cell growth through PTB1/PKM1/PKM2 feedback cascade in colorectal cancer. / Taniguchi, Kohei; Sugito, Nobuhiko; Kumazaki, Minami; Shinohara, Haruka; Yamada, Nami; Nakagawa, Yoshihito; Ito, Yuko; Otsuki, Yoshinori; Uno, Bunji; Uchiyama, Kazuhisa; Akao, Yukihiro.

:: Cancer Letters, 巻 363, 番号 1, 10.07.2015, p. 17-27.

研究成果: Article

TY - JOUR

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.

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