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Int. J. Mol. Sci. 2014, 15(3), 4318-4332; doi:10.3390/ijms15034318
Article

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

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Received: 22 December 2013; in revised form: 10 February 2014 / Accepted: 26 February 2014 / Published: 11 March 2014
(This article belongs to the collection Programmed Cell Death and Apoptosis)
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Abstract: 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.
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

AMA 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. International Journal of Molecular Sciences. 2014; 15(3):4318-4332.

Chicago/Turabian Style

Sun, Yan; Zhao, Xiaoping; Luo, Man; Zhou, Yuhong; Ren, Weiying; Wu, Kefen; Li, Xi; Shen, Jiping; Hu, Yu. 2014. "The Pro-Apoptotic Role of the Regulatory Feedback Loop between miR-124 and PKM1/HNF4α in Colorectal Cancer Cells." Int. J. Mol. Sci. 15, no. 3: 4318-4332.


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