SP1 upregulated FoxO3a promotes tumor progression in colorectal cancer.

Abstract	FoxO transcription factors are important regulators of cell survival in response to a variety of stress stimuli and play vital functions in tumor progression. However, the functions and underlying regulators of FoxO3a in colorectal cancer (CRC) have not been fully elucidated. The aim of the current study was to identify the functions of FoxO3a in CRC and characterize the transcription elements within the promoter region of FoxO3a. The expression of FoxO3a was upregulated in response to hypoxic and oxidative stress stimuli. Furthermore, knockdown of FoxO3a significantly reduced cell proliferation and migration ability, while it promoted the response to cetuximab treatment. In addition, it was revealed that knockdown of FoxO3a reduced tumor progression in vivo. A mechanistic study found that plenty of putative SP1 sites were identified in the FoxO3a promoter. Luciferase reporter assay revealed that a region corresponding to the SP1 binding sites located between ‑2,000 and ‑1,037 bp of FoxO3a promoter was essential for the transcriptional activity. Co-transfection of a SP1 expression vector with the reporter constructs markedly increased luciferase activity. Collectively, these results indicated that SP1‑dependent promoter elements drive FoxO3a gene transcription in colorectal CRC, and indicated that SP1 upregulated FoxO3a is critical for CRC progression.
Authors	Yiyi Yu, Ke Peng, Hong Li, Rongyuan Zhuang, Yan Wang, Wei Li, Shan Yu, Li Liang, Xiaojing Xu, Tianshu Liu
Journal	Oncology reports (Oncol Rep) Vol. 39 Issue 5 Pg. 2235-2242 (May 2018) ISSN: 1791-2431 [Electronic] Greece
PMID	29565456 (Publication Type: Journal Article)
Chemical References	FOXO3 protein, human Forkhead Box Protein O3 Sp1 Transcription Factor SP1 protein, human
Topics	Animals Binding Sites Caco-2 Cells Cell Movement Cell Proliferation Colorectal Neoplasms (genetics, metabolism, pathology) Disease Progression Forkhead Box Protein O3 (chemistry, genetics, metabolism) Gene Expression Regulation, Neoplastic HT29 Cells Humans Mice Neoplasm Transplantation Promoter Regions, Genetic Sp1 Transcription Factor (metabolism) Transcription, Genetic Up-Regulation

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