PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer.

Abstract

Thyroid cancer (TC) is the most common malignant endocrine tumor, and its incidence has progressively increased over several decades. Accumulating evidence has suggested that PFKFB4, a critical regulatory enzyme of glycolysis, has been implicated in various solid cancers. However, the exact effect of PFKFB4 on TC remains unclear. Hence, the objective of this work was to investigate the role of PFKFB4 in TC and explore the underlying regulatory mechanisms. Here, we provide evidence that mRNA levels of PFKFB4 were upregulated in TC patients' thyroids and cell lines. Downregulation of PFKFB4 reduced TC cell viability and inhibited colony formation. In addition, the migration and invasion of TC cells were suppressed by PFKFB4 knockdown, suggesting that PFKFB4 is positively correlated with tumorigenesis of TC. Molecularly, knockdown of PFKFB4 significantly inhibited expression of GCN5 and phosphorylation of PI3K/AKT. Moreover, the suppressive role of shPFKFB4 in TC cell growth was reversed by upregulation of GCN5. Finally, the in vivo experiment indicated that downregulation of PFKF4B suppressed tumor growth in xenografts TC model mice. In total, our results suggested that PFKFB4-mediated TC tumorigenesis by positively regulating GCN5 and PI3K/AKT signaling. These findings provide new research directions and therapeutic options considering PFKF4B as a novel diagnosis marker and therapeutic target.

• Authors: Huanquan Lu, Siyuan Chen, Zhijian You, Chuping Xie, Shichuan Huang, Xiarong Hu
• Journal: Development, growth & differentiation (Dev Growth Differ) Vol. 62 Issue 2 Pg. 129-138 (Feb 2020) ISSN: 1440-169X [Electronic] Japan
• PMID: 31912488 (Publication Type: Journal Article)
• Copyright: © 2020 Japanese Society of Developmental Biologists.

Chemical References

• p300-CBP Transcription Factors
• p300-CBP-associated factor
• Pfkfb4 protein, mouse
• Phosphofructokinase-2

Topics

• Adult
• Animals
• Blotting, Western
• Cell Line, Tumor
• Female
• Humans
• Immunohistochemistry
• In Vitro Techniques
• Male
• Mice, Nude
• Middle Aged
• Phosphofructokinase-2 (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Thyroid Neoplasms (genetics, metabolism, pathology)
• p300-CBP Transcription Factors (genetics, metabolism)