Downregulation of SETD5 Suppresses the Tumorigenicity of Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is an aggressive and incurable cancer. Although understanding of the molecular pathogenesis of HCC has greatly advanced, therapeutic options for the disease remain limited. In this study, we demonstrated that SETD5 expression is positively associated with poor prognosis of HCC and that SETD5 depletion decreased HCC cell proliferation and invasion while inducing cell death. Transcriptome analysis revealed that SETD5 loss downregulated the interferon-mediated inflammatory response in HCC cells. In addition, SETD5 depletion downregulated the expression of a critical glycolysis gene, PKM (pyruvate kinase M1/2), and decreased glycolysis activity in HCC cells. Finally, SETD5 knockdown inhibited tumor growth in xenograft mouse models. These results collectively suggest that SETD5 is involved in the tumorigenic features of HCC cells and that targeting SETD5 may suppress HCC progression.

Automated summary

This study found that SETD5 expression is associated with poor prognosis of HCC, and depletion of SETD5 can reduce HCC cell proliferation and invasion, induce cell death, downregulate interferon-mediated inflammatory response, as well as decrease glycolysis activity in HCC cells, ultimately inhibiting tumor growth in xenograft mouse models.