Forkhead‑box A1 regulates tumor cell growth and predicts prognosis in colorectal cancer

Park,Young‑Lan; Kim,Seung‑Hun; Park,Sun‑Young; Jung,Min‑Woo; Ha,Sang‑Yoon; Choi,Jung‑Ho; Myung,Dae‑Seong; Cho,Sung‑Bum; Lee,Wan‑Sik; Kim,Hyun‑Soo; Joo,Young‑Eun

doi:10.3892/ijo.2019.4771

Forkhead‑box A1 regulates tumor cell growth and predicts prognosis in colorectal cancer

Authors:
- Young‑Lan Park
- Seung‑Hun Kim
- Sun‑Young Park
- Min‑Woo Jung
- Sang‑Yoon Ha
- Jung‑Ho Choi
- Dae‑Seong Myung
- Sung‑Bum Cho
- Wan‑Sik Lee
- Hyun‑Soo Kim
- Young‑Eun Joo
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Affiliations: Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501‑757, Republic of Korea
Published online on: April 4, 2019 https://doi.org/10.3892/ijo.2019.4771
Pages: 2169-2178

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Abstract

Forkhead box A1 (FOXA1) functions as a tumor suppressor gene or an oncogene in various types of cancer; however, the distinct function of FOXA1 in colorectal cancer is unclear. The present study aimed to evaluate whether FOXA1 affects the oncogenic behavior of colorectal cancer cells, and to investigate its prognostic value in colorectal cancer. The impact of FOXA1 on tumor cell behavior was investigated using small interfering RNA and the pcDNA6‑myc vector in human colorectal cancer cell lines. To investigate the role of FOXA1 in the progression of human colorectal cancer, an immunohistochemical technique was used to localize FOXA1 protein in paraffin‑embedded tissue blocks obtained from 403 patients with colorectal cancer. Tumor cell apoptosis and proliferation were evaluated using a terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling assay and Ki‑67 immunohistochemical staining, respectively. FOXA1 knockdown inhibited tumor cell invasion in colorectal cancer cells, and induced apoptosis and cell cycle arrest. FOXA1 knockdown activated cleaved caspase‑poly (ADP‑ribose) polymerase, upregulated the expression of p53 upregulated modulator of apoptosis, and downregulated BH3 interacting domain death agonist and myeloid cell leukemia‑1, leading to the induction of apoptosis. FOXA1 knockdown increased the phosphorylation level of signal transducer and activator of transcription‑3. By contrast, these results were reversed following the overexpression of FOXA1. The overexpression of FOXA1 was associated with differentiation, lymphovascular invasion, advanced tumor stage, depth of invasion, lymph node metastasis and poor survival rate. The mean Ki‑67 labeling index value of FOXA1‑positive tumors was significantly higher than that of FOXA1‑negative tumors. However, no significant association was observed between the expression of FOXA1 and the mean apoptotic index value. These results indicate that FOXA1 is associated with tumor progression via the modulation of tumor cell survival in human colorectal cancer.

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