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Open Access Highly Accessed Research article

MicroRNA-26a regulates glucose metabolism by direct targeting PDHX in colorectal cancer cells

Bing Chen1, Yuling Liu1, Xuewen Jin1, Weiliang Lu1, Jingjing Liu1, Zijing Xia1, Qiong Yuan23, Xia Zhao13, Ningzhi Xu4 and Shufang Liang1*

Author Affiliations

1 State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, No.17, the third section of Renmin South Road, Chengdu 610041, P. R. China

2 Department of Pharmacology, Medical College, Wuhan University of Science and Technology, Wuhan 430065, P. R. China

3 Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, P. R. China

4 Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Sciences, Beijing 100034, P. R. China

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BMC Cancer 2014, 14:443  doi:10.1186/1471-2407-14-443

Published: 16 June 2014

Abstract

Background

Reprogramming energy metabolism has been an emerging hallmark of cancer cells. MicroRNAs play important roles in glucose metabolism.

Methods

The targets of microRNA-26a (miR-26a) were predicted by bioinformatics tools. The efficacy of miR-26a binding the 3′-untranslated region (UTR) of pyruvate dehydrogenase protein X component (PDHX) mRNA was evaluated using a dual-luciferase reporter assay. The PDHX expression at the mRNA and protein level in several colon cancer cell lines was quantified with real-time PCR and Western blot analysis respectively. The effects of miR-26a on glucose metabolism were determined by detecting the content of glucose consumption, production of lactate, pyruvate, and acetyl-coenzyme A.

Results

The expression of miR-26a is inversely associated with the level of its targeting protein PDHX in several colon cancer cell lines with different malignancy potentials. MiR-26a inhibits PDHX expression by direct targeting the 3′-UTR of PDHX mRNA. The glucose consumption and lactate concentration were both greatly increased in colon cancer cells than the normal colon mucosal epithelia under physiological conditions. The overexpression of miR-26a in HCT116 cells efficiently improved the accumulation of pyruvate and decreased the production of acetyl coenzyme A. Meanwhile the inhibition of miR-26a expression induced inverse biological effects.

Conclusions

MiR-26a regulates glucose metabolism of colorectal cancer cells by direct targeting the PDHX, which inhibits the conversion of pyruvate to acetyl coenzyme A in the citric acid cycle.

Keywords:
MicroRNA-26a; PDHX; Colorectal cancer; Glucose metabolism