ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
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
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.
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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