Research Papers:
Transcription factor HBP1 is a direct anti-cancer target of transcription factor FOXO1 in invasive oral cancer
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1807 views | HTML 2913 views | ?
Abstract
Chien-Yi Chan1, Shih-Yi Huang2, Jim Jinn-Chyuan Sheu3,4, Mendel M. Roth5, I-Tai Chou1, Chia-Hsien Lien1, Ming-Fen Lee6,*, Chun-Yin Huang1,4,*
1Department of Nutrition, China Medical University, Taichung, Taiwan
2School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan
3Institute of Biomedical Sciences, National Sun Yatsen University, Kaohsiung, Taiwan
4Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
5GB Lifesciences, San Diego, CA, USA
6Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Taiwan
*These authors contributed equally to this work
Correspondence to:
Chun-Yin Huang, email: [email protected]
Ming-Fen Lee, email: [email protected], [email protected]
Keywords: FOXO1, HBP1, oral cancer
Received: September 16, 2016 Accepted: January 07, 2017 Published: January 14, 2017
ABSTRACT
Either FOXO1 or HBP1 transcription factor is a downstream effector of the PI3K/Akt pathway and associated with tumorigenesis. However, the relationship between FOXO1 and HBP1 in oral cancer remains unclear. Analysis of 30 oral tumor specimens revealed that mean mRNA levels of both FOXO1 and HBP1 in non-invasive and invasive oral tumors were found to be significantly lower than that of the control tissues, and the status of low FOXO1 and HBP1 (< 0.3 fold of the control) was associated with invasiveness of oral tumors. To investigate if HBP1 is a direct transcription target of FOXO1, we searched potential FOXO1 binding sites in the HBP1 promoter using the MAPPER Search Engine, and two putative FOXO1 binding sites located in the HBP1 promoter –132 to –125 bp and –343 to –336 bp were predicted. These binding sites were then confirmed by both reporter gene assays and the in cellulo ChIP assay. In addition, Akt activity manipulated by PI3K inhibitor LY294002 or Akt mutants was shown to negatively affect FOXO1-mediated HBP1 promoter activation and gene expression. Last, the biological significance of the FOXO1-HBP1 axis in oral cancer malignancy was evaluated in cell growth, colony formation, and invasiveness. The results indicated that HBP1 knockdown potently promoted malignant phenotypes of oral cancer and the suppressive effect of FOXO1 on cell growth, colony formation, and invasion was alleviated upon HBP1 knockdown in invasive oral cancer cells. Taken together, our data provide evidence for HBP1 as a direct downstream target of FOXO1 in oral cancer malignancy.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 14653