Next Article in Journal
Comparative Proteomic Analysis of Differential Responses of Pinus massoniana and Taxus wallichiana var. mairei to Simulated Acid Rain
Next Article in Special Issue
Sphingolipids: Key Regulators of Apoptosis and Pivotal Players in Cancer Drug Resistance
Previous Article in Journal
The Effect of Physical and Chemical Cues on Hepatocellular Function and Morphology
Previous Article in Special Issue
Mitochondria in the Center of Human Eosinophil Apoptosis and Survival
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2014, 15(3), 4318-4332;

The Pro-Apoptotic Role of the Regulatory Feedback Loop between miR-124 and PKM1/HNF4α in Colorectal Cancer Cells

Department of Geriatrics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China
Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 22 December 2013 / Revised: 10 February 2014 / Accepted: 26 February 2014 / Published: 11 March 2014
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
Full-Text   |   PDF [1573 KB, uploaded 19 June 2014]


Accumulating evidence indicates that miRNA regulatory circuits play important roles in tumorigenesis. We previously reported that miR-124 is correlated with prognosis of colorectal cancer due to PKM-dependent regulation of glycolysis. However, the mechanism by which miR-124 regulates apoptosis in colorectal cancer remains largely elusive. Here, we show that miR-124 induced significant apoptosis in a panel of colorectal cancer cell lines. The mitochondrial apoptosis pathway was activated by miR-124. Furthermore, the pro-apoptotic role of miR-124 was dependent on the status of PKM1/2 level. PKM1 was required for miR-124-induced apoptosis. Via direct protein-protein interaction, PKM1 promoted HNF4α binding to the promoter region of miR-124 and transcribing miR-124. Moreover, HNF4α or PKM1 had a more dramatic effect on colorectal cancer cell apoptosis in the presence of miR-124. However, inhibition of miR-124 blocked cell apoptosis induced by HNF4α or PKM1. These data indicate that miR-124 not only alters the expression of genes involved in glucose metabolism but also stimulates cancer cell apoptosis. In addition, the positive feedback loop between miR-124 and PKM1/HNF4α plays an important role in colorectal cancer cell apoptosis; it suggests that disrupting this regulatory circuit might be a potential therapeutic tool for colorectal cancer treatment. View Full-Text
Keywords: PKM; HNF4α; miR-124; colorectal cancer PKM; HNF4α; miR-124; colorectal cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Sun, Y.; Zhao, X.; Luo, M.; Zhou, Y.; Ren, W.; Wu, K.; Li, X.; Shen, J.; Hu, Y. The Pro-Apoptotic Role of the Regulatory Feedback Loop between miR-124 and PKM1/HNF4α in Colorectal Cancer Cells. Int. J. Mol. Sci. 2014, 15, 4318-4332.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top