2. Academic Validation
  3. HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1

HNF1A regulates oxaliplatin resistance in pancreatic cancer by targeting 53BP1

  • Int J Oncol. 2023 Apr;62(4):45. doi: 10.3892/ijo.2023.5493.
Renpeng Xia # 1,  Chonghui Hu # 2,  Yuancheng Ye # 1,  Xiang Zhang 3,  Tingting Li 4,  Rihua He 2,  Shangyou Zheng 2,  Xiaofeng Wen 5,  Rufu Chen 1
Affiliations

Affiliations

  • 1 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
  • 2 Department of Pancreas Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China.
  • 3 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510120, P.R. China.
  • 4 School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P.R. China.
  • 5 Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510655, P.R. China.
  • # Contributed equally.
PMID: 36825600 DOI: 10.3892/ijo.2023.5493
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.

Keywords

DNA repair; PDAC; chemoresistance; hepatocyte nuclear factor 1 homeobox A; p53‑binding protein 1.

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