EZH2 regulates pancreatic cancer cells through E2F1, GLI1, CDK3, and Mcm4

Hereditas. 2023 May 17;160(1):23. doi: 10.1186/s41065-023-00280-1.

Abstract

Pancreatic cancer (PC) is one of the most common malignant tumors in digestive tract. To explore the role of epigenetic factor EZH2 in the malignant proliferation of PC, so as to provide effective medical help in PC. Sixty paraffin sections of PC were collected and the expression of EZH2 in PC tissues was detected by immunohistochemical assay. Three normal pancreas tissue samples were used as controls. The regulation of EZH2 gene on proliferation and migration of normal pancreatic cell and PC cell were determined by MTS, colony forming, Ki-67 antibody, scratch and Transwell assays. Through differential gene annotation and differential gene signaling pathway analysis, differentially expressed genes related to cell proliferation were selected and verified by RT-qPCR. EZH2 is mainly expressed in the nuclei of pancreatic tumor cells, but not in normal pancreatic cells. The results of cell function experiments showed that EZH2 overexpression could enhance the proliferation and migration ability of PC cell BXPC-3. Cell proliferation ability increased by 38% compared to the control group. EZH2 knockdown resulted in reduced proliferation and migration ability of cells. Compared with control, proliferation ability of cells reduced by 16%-40%. The results of bioinformatics analysis of transcriptome data and RT-qPCR demonstrated that EZH2 could regulate the expression of E2F1, GLI1, CDK3 and Mcm4 in normal and PC cells. The results revealed that EZH2 might regulate the proliferation of normal pancreatic cell and PC cell through E2F1, GLI1, CDK3 and Mcm4.

Keywords: EZH2; Migration; PC; Proliferation; Transcriptome.

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 3 / metabolism
  • E2F1 Transcription Factor / metabolism
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Humans
  • Minichromosome Maintenance Complex Component 4 / metabolism
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Zinc Finger Protein GLI1 / metabolism

Substances

  • Zinc Finger Protein GLI1
  • MCM4 protein, human
  • Minichromosome Maintenance Complex Component 4
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • CDK3 protein, human
  • Cyclin-Dependent Kinase 3
  • GLI1 protein, human
  • E2F1 protein, human
  • E2F1 Transcription Factor