Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells

Zou, Naiyi; Zhang, Xueyuan; Li, Shuguang; Li, Youmei; Zhao, Yan; Yang, Xingxiao; Zhu, Shuchai

doi:10.7150/jca.58023

International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

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J Cancer 2021; 12(16):5013-5024. doi:10.7150/jca.58023 This issue Cite

Research Paper

Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells

Naiyi Zou¹, Xueyuan Zhang¹, Shuguang Li¹, Youmei Li¹, Yan Zhao¹, Xingxiao Yang², Shuchai Zhu^1✉

1. Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
2. Department of Infection Management, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Citation:

Zou N, Zhang X, Li S, Li Y, Zhao Y, Yang X, Zhu S. Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells. J Cancer 2021; 12(16):5013-5024. doi:10.7150/jca.58023. https://www.jcancer.org/v12p5013.htm

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Abstract

Purpose: Radiotherapy is a major modality for treatment of local advanced esophageal squamous cell carcinoma (ESCC). Hepatocyte nuclear factor 1-alpha (HNF1A) is involved in regulation of tumor cell proliferation, apoptosis, cycle distribution, invasion metastasis and chemical resistance. The aim of this study was to investigate the effect of HNF1A on radiosensitivity of ESCC cells.

Methods: In our study, HNF1A expression was verified from GEPIA in multiple types of cancer. The prognostic value of HNF1A in ESCC was obtained by TCGA database. In addition, the expression of HNF1A in ESCC cell lines was verified by western blot. Subsequently, lentiviruses were used to construct HNF1A overexpressed cell lines TE1 and KYSE150.Then, the roles of HNF1A on cell proliferation, invasion, apoptosis, cell cycle distribution and radiosensitivity were verified. Furthermore, the relationship between HNF1A and γH2AX were determined by western blot and immunofluorescence. We also detected the expression changes of key factors in PI3K/AKT pathway after overexpression of HNF1A.

Results: The results showed that the overexpression of HNF1A promoted cell proliferation and invasion with or without irradiation (IR), and potently radiation-resistance ESCC cells with a sensitization enhancement ratio (SER) of 0.76 and 0.87. In addition, HNF1A regulated Cyclin D1 and CDK4 proteins to promote the transition from radiation-induced G0/G1 phase arrest to S phase, and coordinated BAX and BCL2 proteins to reduce the occurrence of radiation-induced apoptosis. It was worth noting that HNF1A might be involved in radiation-induced DNA damage repair by regulating γH2AX though PI3K/AKT signal pathway.

Conclusion: Our study preliminarily suggested that HNF1A was associated with the progression and radiosensitivity of ESCC cells, and it might reduce the radiosensitivity of ESCC cells by promoting cell proliferation, releasing G0/G1 phase arrest, reducing apoptosis, and regulating the expression of γH2AX protein though driving PI3K/AKT signal pathway.

Keywords: ESCC, HNF1A, proliferation, metastasis, γH2AX, PI3K/AKT pathway

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APA

Zou, N., Zhang, X., Li, S., Li, Y., Zhao, Y., Yang, X., Zhu, S. (2021). Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells. Journal of Cancer, 12(16), 5013-5024. https://doi.org/10.7150/jca.58023.

ACS

Zou, N.; Zhang, X.; Li, S.; Li, Y.; Zhao, Y.; Yang, X.; Zhu, S. Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells. J. Cancer 2021, 12 (16), 5013-5024. DOI: 10.7150/jca.58023.

NLM

CSE

Zou N, Zhang X, Li S, Li Y, Zhao Y, Yang X, Zhu S. 2021. Elevated HNF1A expression promotes radiation-resistance via driving PI3K/AKT signaling pathway in esophageal squamous cell carcinoma cells. J Cancer. 12(16):5013-5024.

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