Peroxisomal trans-2-enoyl-CoA inhibits proliferation, migration and invasion of hepatocellular carcinoma cells

Acta Histochem. 2023 Feb;125(2):152002. doi: 10.1016/j.acthis.2023.152002. Epub 2023 Jan 30.

Abstract

Objectives: Peroxisomal trans-2-enoyl-CoA reductase (PECR) encodes proteins related to fatty acid metabolism and synthesis. It has been confirmed that PECR has decreased expression in colon cancer and breast cancer, while the role of PECR in liver cancer is unknown. We aimed to study the role and mechanism of PECR in the genesis and development of liver cancer.

Methods: In this study, the expression of PECR was queried in the Cancer Genome Atlas Database and Western Blotting and RT-PCR experiments were carried out in paired liver cancer tissues to detect the expression of PECR. Functional tests were evaluated by cell count kit-8 (CCK-8), Flow cytometry, wound healing assay, Transwell, migration. In vivo study, we constructed a nude mouse tumorigenic model to observe the effect of PECR on the proliferation of liver cancer. And the tumor body of the mouse was taken out for histochemistry (IHC). Multiple Cox regression was used to analyze the correlation between PECR and Clinicopathology.

Results: We confirmed that the overexpression of PECR inhibited the proliferation, migration and invasion of hepatocellular carcinoma and promoted the apoptosis of hepatocellular carcinoma. The low expression group of PECR promoted the proliferation and metastasis of liver cancer. In vivo, overexpression of PECR inhibits the proliferation of mouse tumors. In addition, the mechanism study shows that PECR may indirectly affect the proliferation of hepatocellular carcinoma cells through ERK pathway.

Conclusion: In general, PECR may be a new diagnostic marker and a potential therapeutic target for hepatocellular carcinoma.

Keywords: Hepatocellular carcinoma; MAPK; Molecular markers; PECR; Prognosis; Proliferation.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Liver Neoplasms* / pathology
  • Mice
  • MicroRNAs* / genetics
  • Neoplasm Invasiveness / genetics
  • Oxidoreductases Acting on CH-CH Group Donors* / metabolism

Substances

  • MicroRNAs
  • trans-2-enoyl-CoA reductase (NADPH)
  • Oxidoreductases Acting on CH-CH Group Donors