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

International Journal of Molecular Sciences

Yan Sun³  Xiaoping Zhao¹  Man Luo³  Yuhong Zhou²  Weiying Ren³  Kefen Wu³  Xi Li³  Jiping Shen³ 

[1] Department of Nuclear Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; E-Mail:;Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; E-Mail:;Department of Geriatrics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China; E-Mails:

关键词: PKM;    HNF4α;    miR-124;    colorectal cancer;   

DOI  :  10.3390/ijms15034318

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland