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

被引：172

作者：

Taniguchi, Kohei ^{[1
,2
]}

Sugito, Nobuhiko ^{[1
]}

Kumazaki, Minami ^{[1
]}

Shinohara, Haruka ^{[1
]}

Yamada, Nami ^{[1
]}

Nakagawa, Yoshihito ^{[3
]}

Ito, Yuko ^{[4
]}

Otsuki, Yoshinori ^{[4
]}

Uno, Bunji ^{[1
]}

Uchiyama, Kazuhisa ^{[2
]}

Akao, Yukihiro ^{[1
]}

机构：

[1] Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan

[2] Osaka Med Coll, Dept Gen & Gastroenterol Surg, Takatsuki, Osaka 5698686, Japan

[3] Fujita Hlth Univ, Sch Med, Dept Gastroenterol, Toyoake, Aichi 4701192, Japan

[4] Osaka Med Coll, Div Life Sci, Dept Anat & Cell Biol, Takatsuki, Osaka 5698686, Japan

来源：

CANCER LETTERS | 2015年 / 363卷 / 01期

关键词：

miR-124; PTB1; PKM; Warburg effect; Colorectal cancer; PYRUVATE-KINASE; DOWN-REGULATION; MIR-124; EXPRESSION; METABOLISM; APOPTOSIS; RCK/P54; PROTEIN; GENE;

D O I：

10.1016/j.canlet.2015.03.026

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 I 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：17 / 27

页数：11

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