Carboxypeptidase E down-regulation regulates transcriptional and epigenetic profiles in pancreatic cancer cell line: A network analysis

Cancer Biomark. 2020;29(1):79-88. doi: 10.3233/CBM-191163.


Background: Pancreatic cancer is a malignant tumor and its incidence has increased in recent years. Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme that has been shown to be associated with tumor growth and invasion in various cancers including pancreatic cancer.

Objective: To understand the molecular mechanism underlying the proliferative effects of CPE in cancer cells.

Methods: We down-regulated CPE gene expression in PANC-1 cell, a pancreatic cell line, and investigated mRNA, miRNA, circRNA and lncRNA expression profiling in PANC-1 cells from control group and CPE knock-down group by microarray analysis. We further validated the top 14 differentially expressed circRNAs by qRT-PCR.

Results: Our results showed that CPE down-regulation caused decreased cell proliferation. The microarray data showed 107, 15, 299 and 360 differentially expressed mRNAs, miRNAs, circRNAs, and lncRNAs, respectively between control group and CPE knock-down group. Of Which, 41 mRNAs, 12 miRNAs, 133 circRNAs, and 262 lncRNAs were down-regulated; 66 mRNAs, 3 miRNAs, 166 circRNAs, and 98 lncRNAs were up-regulated. Bioinformatics analysis showed that the top significantly enriched pathways for the differentially expressed RNAs were related to cancer onset and/or progression, these included p53 signaling pathway, ECM-receptor interaction, focal adhesion and Wnt signaling pathway. We further performed network analysis to assess the mRNA, miRNA, circRNA and lncRNA correlations, and showed that HUWE1, hsa-miR-6780b-5p, has_circ_0058208 and lnc-G3BP1-3:8 were in the core position of the network.

Conclusions: Taken together, these results identified potential CPE regulated core genes and pathways for cell proliferation in pancreatic cancer cell, and therefore provide potential targets for the treatment of pancreatic cancer.

Keywords: Carboxypeptidase E; Pancreatic cancer; ceRNA analysis.

MeSH terms

  • Carboxypeptidase H / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Computational Biology
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Regulatory Networks / genetics
  • Humans
  • MicroRNAs / genetics
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • RNA, Circular / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / genetics
  • Signal Transduction / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics


  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • HUWE1 protein, human
  • Ubiquitin-Protein Ligases
  • Carboxypeptidase H