Tumor-Promoting Actions of HNRNP A1 in HCC Are Associated with Cell Cycle, Mitochondrial Dynamics, and Necroptosis

Int J Mol Sci. 2022 Sep 6;23(18):10209. doi: 10.3390/ijms231810209.

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. Although increasing evidence supports the role of heterogeneous ribonucleoprotein particle A1 (HNRNP A1) in tumor progression, the function of HNRNP A1 in HCC remains unclear. Here, we focused on the role of HNRNP A1 in the development of HCC. In this study, we found HNRNP A1 participates in many aspects of HCC, such as progression and prognosis. Our results showed that HNRNP A1 is upregulated in human HCC tissues and cell lines. High expression of HNRNP A1 can promote the proliferation, migration, and invasion in HCC cells and accelerate tumor progression in mice. Moreover, we found that HNRNP A1 prevents the senescence process of HCC cells. Knocking down of HNRNP A1 promotes the expression of P16INK4, which arrests the cell cycle and then induces the senescence phenotype in HCC cells. Furthermore, we found that HNRNP A1 regulated necroptosis and mitochondrial dynamics. In summary, our study indicates that HNRNP A1 promotes the development of HCC, which suggests a potential therapeutic target for HCC.

Keywords: HCC; HNRNP A1; P16INK4; cell cycle; cell senescence.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / metabolism
  • Cell Cycle
  • Heterogeneous Nuclear Ribonucleoprotein A1 / metabolism*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Humans
  • Liver Neoplasms* / metabolism
  • Mice
  • Mitochondrial Dynamics
  • Necroptosis
  • Ribonucleoproteins

Substances

  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Ribonucleoproteins
  • hnRNPA1 protein, human

Grants and funding

Supported by the National-Natural Science Foundation (81870348) and the Nanjing Medical Key Science and Technology Development Project (ZKX19019).