J Cancer 2021; 12(6):1634-1643. doi:10.7150/jca.49231

Research Paper

DNA methylation integratedly modulates the expression of Pit-Oct-Unt transcription factors in esophageal squamous cell carcinoma

Wei He1✉, Shuai Gong1, Xin Wang2, Xinhua Dong3, Hua Cheng4

1. Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan province, China.
2. Department of Radiotherapy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan province, China.
3. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan province, China.
4. Department of Oncology, Xiayi Hospital of Traditional Chinese Medicine. Shangqiu 476400, Henan province, China.

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Citation:
He W, Gong S, Wang X, Dong X, Cheng H. DNA methylation integratedly modulates the expression of Pit-Oct-Unt transcription factors in esophageal squamous cell carcinoma. J Cancer 2021; 12(6):1634-1643. doi:10.7150/jca.49231. Available from https://www.jcancer.org/v12p1634.htm

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Abstract

Background: Dysregulation of Pit-Oct-Unc family transcription factors has been implicated in esophageal squamous cell carcinoma (ESCC). In this study, we evaluated the expression and promoter methylation status of Octamer (OCT) transcription factor genes in human ESCC clinical specimens to investigate the mechanism underlying this observation along with the clinical significance.

Methods: Total DNA or RNA was extracted from ESCC tissue specimens and the mRNA level of genes encoding the transcription factors OCT1, OCT2, OCT3/OCT4, OCT5, OCT7, OCT9, and OCT11 were evaluated by quantitative PCR. The DNA methylation status of gene promoters was assessed by bisulfite pyrosequencing and next-generation sequencing. The relationship between the expression of these transcription factors and ESCC proliferation was investigated in vitro and in vivo with the colony formation assay and a mouse xenograft tumor model, respectively. We also examined the correlation between OCT gene expression and promoter methylation and clinicopathologic characteristics of ESCC.

Results: OCT1 was upregulated whereas OCT4, OCT6, and OCT11 were downregulated in ESCC compared to non-tumor tissue. OCT2, OCT7, and OCT9 were undetected in all samples. OCT1, OCT6, and OCT11 levels were negatively correlated with the methylation of their respective promoters, but there was no relationship between OCT4 expression and promoter methylation status.

Conclusion: Changes in promoter methylation rate underlie the observed alterations in OCT1, OCT6, and OCT11 expression in ESCC, whereas another mechanism is likely responsible for the dysregulation of OCT4.

Keywords: OCT transcription factor, DNA methylation, esophageal squamous cell carcinoma, clinical characteristics