METTL3 Promotes Immature Dental Pulp Stem Cells-induced Angiogenesis by Regulating ETS1 MRNA Stability in an MA-HuR-dependent Manner

Overview

Journal Odontology

Specialty Dentistry

Date 2024 Jul 5

PMID 38969870

Authors

Jian Qin

Li Zou

Fachao Lu

Fang Liu

Qian Min

Lilei Zhu

Affiliations

Soon will be listed here.

Abstract

Angiogenesis serves as the determinate element of pulp regeneration. Dental pulp stem cell (DPSC) implantation can promote the regeneration of dental pulp tissue. Herein, the role of mA methyltransferase methyltransferase-like 3 (METTL3) in regulating DPSCs-induced angiogenesis during pulp regeneration therapy was investigated. Cell DPSC viability, HUVEC migration, and angiogenesis ability were analyzed by CCK-8 assay, wound healing, Transwell assay, and tube formation assay. The global and EST1 mRNA m6A levels were detected by mA dot blot and Me-RIP. The interactions between E26 transformation-specific proto-oncogene 1(ETS1), human antigen R(HuR), and METTL3 were analyzed by RIP assay. The relationship between METTL3 and the mA site of ETS1 was performed by dual-luciferase reporter assay. ETS1 mRNA stability was examined with actinomycin D. Herein, our results revealed that human immature DPSCs (hIDPSCs) showed stronger ability to induce angiogenesis than human mature DPSCs (hMDPSCs), which might be related to ETS1 upregulation. ETS1 knockdown inhibited DPSCs-induced angiogenesis. Our mechanistic experiments demonstrated that METTL3 increased ETS1 mRNA stability and expression level on DPSCs in an mA-HuR-dependent manner. ETS1 upregulation abolished sh-METTL3's inhibition on DPSCs-induced angiogenesis. METTL3 upregulation promoted DPSCs-induced angiogenesis by enhancing ETS1 mRNA stability in an mA-HuR-dependent manner. This study reveals a new mechanism by which mA methylation regulates angiogenesis in DPSCs, providing new insights for stem cell-based tissue engineering.

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