BAIAP2L2 promotes the malignancy of hepatocellular carcinoma via GABPB1-mediated reactive oxygen species imbalance

Cancer Gene Ther. 2024 Dec;31(12):1868-1883. doi: 10.1038/s41417-024-00841-0. Epub 2024 Nov 4.

Abstract

Hepatocellular carcinoma (HCC) is a common type of cancer worldwide and ranks as the fourth leading cause of cancer-related deaths. This research investigation identified an upregulation of BAI1-associated protein 2-like 2 (BAIAP2L2) in HCC tissues, which was found to be an independent prognostic factor for overall survival in HCC patients. BAIAP2L2 was observed to enhance cell proliferation, metastasis, stemness, cell cycle progression, and inhibit apoptosis in HCC. Mechanistically, NFκB1 was found to stimulate BAIAP2L2 transcription by directly binding to its promoter region. BAIAP2L2 interacts with GABPB1 to inhibit its ubiquitin-mediated degradation and promote its nuclear translocation. BAIAP2L2 inhibits the levels of reactive oxygen species (ROS) by regulating GABPB1, thereby promoting cancer properties in HCC and reducing the sensitivity of HCC to lenvatinib. In summary, this study elucidates the role and underlying mechanism of BAIAP2L2 in HCC, providing a potential biomarker and therapeutic target for this disease.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • GA-Binding Protein Transcription Factor / genetics
  • GA-Binding Protein Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • Mice
  • Middle Aged
  • Prognosis
  • Reactive Oxygen Species* / metabolism

Substances

  • Reactive Oxygen Species
  • GABPB1 protein, human
  • GA-Binding Protein Transcription Factor