GroEL of Porphyromonas gingivalis-induced microRNAs accelerate tumor neovascularization by downregulating thrombomodulin expression in endothelial progenitor cells

Feng Yen Lin, Yi Ting Tsai, Chun Yao Huang, Ze Hao Lai, Chien Sung Tsai, Chun Ming Shih, Cheng Yen Lin, Yi Wen Lin

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

We found that GroEL in Porphyromonas gingivalis accelerated tumor growth and increased mortality in tumor-bearing mice; GroEL promoted proangiogenic function, which may be the reason for promoting tumor growth. To understand the regulatory mechanisms by which GroEL increases the proangiogenic function of endothelial progenitor cells (EPCs), we explored in this study. In EPCs, MTT assay, wound-healing assay, and tube formation assay were performed to analyze its activity. Western blot and immunoprecipitation were used to study the protein expression along with next-generation sequencing for miRNA expression. Finally, a murine tumorigenesis animal model was used to confirm the results of in vitro. The results indicated that thrombomodulin (TM) direct interacts with PI3K/Akt to inhibit the activation of signaling pathways. When the expression of TM is decreased by GroEL stimulation, molecules in the PI3K/Akt signaling axis are released and activated, resulting in increased migration and tube formation of EPCs. In addition, GroEL inhibits TM mRNA expression by activating miR-1248, miR-1291, and miR-5701. Losing the functions of miR-1248, miR-1291, and miR-5701 can effectively alleviate the GroEL-induced decrease in TM protein levels and inhibit the proangiogenic abilities of EPCs. These results were also confirmed in animal experiments. In conclusion, the intracellular domain of the TM of EPCs plays a negative regulatory role in the proangiogenic capabilities of EPCs, mainly through direct interaction between TM and PI3K/Akt to inhibit the activation of signaling pathways. The effects of GroEL on tumor growth can be reduced by inhibiting the proangiogenic properties of EPCs through the inhibition of the expression of specific miRNAs.

Original languageEnglish
Pages (from-to)47-61
Number of pages15
JournalMolecular Oral Microbiology
Volume39
Issue number2
DOIs
Publication statusAccepted/In press - 2023

Keywords

  • 8
  • endothelial progenitor cell
  • GroEL
  • MiRNA
  • P. gingivalis
  • thrombomodulin

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • General Dentistry
  • Microbiology (medical)

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