Proto-Oncogene FAM50A Can Regulate the Immune Microenvironment and Development of Hepatocellular Carcinoma In Vitro and In Vivo

Int J Mol Sci. 2023 Feb 6;24(4):3217. doi: 10.3390/ijms24043217.

Abstract

Hepatocellular carcinoma (HCC) is a vital global health problem. The characteristics are high morbidity, high mortality, difficulty in early diagnosis and insensitivity to chemotherapy. The main therapeutic schemes for treating HCC mainly include Tyrosine kinase inhibitors represented by sorafenib and lenvatinib. In recent years, immunotherapy for HCC has also achieved certain results. However, a great number of patients failed to benefit from systemic therapies. FAM50A belongs to the FAM50 family and can be used as a DNA-binding protein or transcription factor. It may take part in the splicing of RNA precursors. In studies of cancer, FAM50A has been demonstrated to participate in the progression of myeloid breast cancer and chronic lymphocytic leukemia. However, the effect of FAM50A on HCC is still unknown. In this study, we have demonstrated the cancer-promoting effects and diagnostic value of FAM50A in HCC using multiple databases and surgical samples. We identified the role of FAM50A in the tumor immune microenvironment (TIME) and immunotherapy efficacy in HCC. We also proved the effects of FAM50A on the malignancy of HCC in vitro and in vivo. In conclusion, we confirmed that FAM50A is an important proto-oncogene in HCC. FAM50A acts as a diagnostic marker, immunomodulator and therapeutic target for HCC.

Keywords: FAM50A; apoptosis; cell cycle; epithelial–mesenchymal transition; hepatocellular carcinoma; immune cell infiltration; malignancy; prognostic value; stemness degree; xenotransplanted tumor.

MeSH terms

  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • DNA-Binding Proteins / metabolism
  • Humans
  • Liver Neoplasms* / metabolism
  • RNA-Binding Proteins
  • Sorafenib / pharmacology
  • Tumor Microenvironment

Substances

  • Sorafenib
  • FAM50A protein, human
  • DNA-Binding Proteins
  • RNA-Binding Proteins