Open Access

HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1

  • Authors:
    • Renpeng Xia
    • Chonghui Hu
    • Yuancheng Ye
    • Xiang Zhang
    • Tingting Li
    • Rihua He
    • Shangyou Zheng
    • Xiaofeng Wen
    • Rufu Chen
  • View Affiliations

  • Published online on: February 22, 2023     https://doi.org/10.3892/ijo.2023.5493
  • Article Number: 45
  • Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

DNA double‑strand break repair is critically involved in oxaliplatin resistance in pancreatic ductal adenocarcinoma (PDAC). Hepatocyte nuclear factor 1 homeobox A (HNF1A) has received increased attention regarding its role in cancer progression. The present study explored the role of HNF1A in oxaliplatin resistance in PDAC. The results revealed that HNF1A expression was negatively associated with oxaliplatin chemoresistance in PDAC tissues and cell lines. HNF1A inhibition promoted the proliferation, colony formation and stemness of PDAC cells, and suppressed their apoptosis. Furthermore, HNF1A inhibition switched nonhomologous end joining to homologous recombination, thereby enhancing genomic stability and oxaliplatin resistance. Mechanistically, HNF1A transcriptionally activates p53‑binding protein 1 (53BP1) expression by directly interacting with the 53BP1 promoter region. Upregulation of HNF1A and 53BP1 induced significant inhibition of PDAC growth and oxaliplatin resistance in patient‑derived PDAC xenograft models and orthotopic models. In conclusion, the findings of the present study suggested that HNF1A/53BP1 may be a promising PDAC therapeutic target for overcoming oxaliplatin resistance.
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April-2023
Volume 62 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Xia R, Hu C, Ye Y, Zhang X, Li T, He R, Zheng S, Wen X and Chen R: HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1. Int J Oncol 62: 45, 2023
APA
Xia, R., Hu, C., Ye, Y., Zhang, X., Li, T., He, R. ... Chen, R. (2023). HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1. International Journal of Oncology, 62, 45. https://doi.org/10.3892/ijo.2023.5493
MLA
Xia, R., Hu, C., Ye, Y., Zhang, X., Li, T., He, R., Zheng, S., Wen, X., Chen, R."HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1". International Journal of Oncology 62.4 (2023): 45.
Chicago
Xia, R., Hu, C., Ye, Y., Zhang, X., Li, T., He, R., Zheng, S., Wen, X., Chen, R."HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1". International Journal of Oncology 62, no. 4 (2023): 45. https://doi.org/10.3892/ijo.2023.5493