2. Academic Validation
  3. MCP-1 facilitates VEGF production by removing miR-374b-5p blocking of VEGF mRNA translation

MCP-1 facilitates VEGF production by removing miR-374b-5p blocking of VEGF mRNA translation

  • Biochem Pharmacol. 2022 Dec:206:115334. doi: 10.1016/j.bcp.2022.115334.
Huan-Yu Zhao 1,  Yi-Pan Zhu 2,  Ying Wen 2,  Xin-Yu Ding 2,  Jing Sun 2,  Ren-Peng Ji 2,  Qiu-Ju Han 2,  Lu-Yuan Li 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, The Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China; Department of Pharmacology, Second Military Medical University/Naval Medical University, Shanghai 200433, China.
  • 2 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, The Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China.
  • 3 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, The Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China. Electronic address: [email protected].
PMID: 36328133 DOI: 10.1016/j.bcp.2022.115334
Abstract

Monocyte chemotactic protein-1 (MCP-1) is known to be able to facilitate vascular endothelial growth factor (VEGF) gene expression, hence promoting vascular hyperpermeability and neovascularization. We show here that a MicroRNA molecule, miR-374b-5p can target the 3'-untranslated region of the VEGF mRNA, thus preventing VEGF production. Additionally, MCP-1 promotes the acetylation of transcription factor STAT3 at Lys685, which facilitates the formation of an ac-stat3-DNA methyltransferase-histone methyltransferase complex (ac-stat3/DNMT1/EZH2) that binds to the promoter of the miR-374b-5p gene. This results in diminished miR-374b-5p expression and enhanced VEGF production. Moreover, treatment of appropriate animal models either with a miR-374b-5p mimicry or with inhibitors of either STAT3 acetylation, DNMT1, or EZH2, leads to marked inhibition of MCP-1-promoted neovascularization and tumor growth. These findings indicate that MCP-1 facilitated inhibition of miR-374b-5p gene expression leads to the removal of a block of VEGF mRNA translation by miR-374b-5p. This mechanism could be of importance in the modulation of inflammatory conditions.

Keywords

Angiogenesis; Epigenetic modification; MCP-1; VEGF; miRNA.

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