miR-6807-5p Inhibited the Odontogenic Differentiation of Human Dental Pulp Stem Cells Through Directly Targeting METTL7A

Abstract

Background: Tooth tissue regeneration mediated by mesenchymal stem cells (MSCs) has become the most ideal treatment. Although the known regulatory mechanism and some achievements have been discovered, directional differentiation cannot effectively induce regeneration of tooth tissue. In this study, we intended to explore the function and mechanism of miR-6807-5p and its target gene METTL7A in odontogenic differentiation.Methods: In this study, human dental pulp stem cells (DPSCs) were used. Alkaline phosphatase (ALP), Alizarin red staining (ARS), and calcium ion quantification were used to detect the odontogenic differentiation of miR-6807-5p and METTL7A. Real-time RT-PCR, western blot, dual-luciferase reporter assay, and pull-down assay with biotinylated miRNA were used to confirm that METTL7A was the downstream gene of miR-6807-5p. Protein mass spectrometry and co-immunoprecipitation (Co-IP) were used to detect that SNRNP200 was the co-binding protein of METTL7A.Results: After mineralized induction, the odontogenic differentiation was enhanced in the miR-6807-5p-knockdown group and weakened in the miR-6807-5p-overexpressed group compared with the control group. METTL7A was the downstream target of miR-6807-5p. After mineralized induction, the odontogenic differentiation was weakened in the METTL7A-knockdown group and enhanced in the METTL7A-overexpressed group compared with the control group. SNRNP200 was the co-binding protein of METTL7A. The knockdown of SNRNP200 inhibited the odontogenic differentiation of DPSCs.Conclusion: This study verified that miR-6807-5p inhibited the odontogenic differentiation of DPSCs. The binding site of miR-6807-5p was the 3′UTR region of METTL7A, which was silenced by miR-6807-5p. METTL7A promoted the odontogenic differentiation of DPSCs. SNRNP200, a co-binding protein of METTL7A, promoted the odontogenic differentiation of DPSCs.

Transcriptomic characterization revealed that METTL7A inhibits melanoma progression via the p53 signaling pathway and immunomodulatory pathway

“… Nain et al (2021) determined downregulation of METTL7A expression in sufferers with COVID-19 patient. Wang et al (2021a) confirmed that METTL7A promotes odontogenic differentiation of human dental pulp stem cells. In addition, abnormal expression of METTL7A has been detected in thyroid ( Zhou et al, 2017 ), choriocarcinoma ( Jun et al, 2020 ), gastric ( Sexton et al, 2020 ), osteosarcoma ( Jia et al, 2021 ), Lung adenocarcinoma ( Guo, Ma & Zhou, 2019 ), breast ( McKinnon & Mellor, 2017 ), and colorectal cancers ( Lacalamita et al, 2021 ).…”

Promotive Effect of FBXO32 on the Odontoblastic Differentiation of Human Dental Pulp Stem Cells

“…In brief, β-TCP blocks (5 mm × 5 mm × 2 mm, Biological Materials Manufacturing Core, Sichuan University) were soaked in GM and incubated for 30 min at 37 • C. Then the FBXO32-KD/NC-KD hDPSCs were suspended and loaded onto the β-TCP blocks at 1 × 10 6 cells per block, and the β-TCP/hDPSCs composites were statically incubated for 2 h. After that, each composite was transferred into a 24-well plate and cultured for 24 h with 1 mL DM. Finally, the composites were subcutaneously transplanted into nude mice for 8 weeks as previously described [10,12,78]. Then mice (n = 4, each group) were sacrificed, and composites were harvested.…”

“…Previous studies have investigated the underlying mechanisms of the involvement of DPSCs in dentinogenesis, including epigenetic mechanisms [6][7][8][9][10], involvement of growth factors [11][12][13][14], and iron homeostasis [15][16][17][18][19]. Dentinogenesis and osteogenesis share many similarities, including genes that regulate odontoblastic and osteogenic differentiation, conversion processes from unmineralized predentin to dentin and osteoid to bone, and mineralization mechanisms, such as hormonal regulation [20,21].…”

METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation

“…MicroRNA (miRNA) is a class of noncoding singlestranded RNA molecule, which plays an important role in many aspects of biological functions [7][8][9]. Our previous study indicated that miR-196b-5p inhibited cell proliferation and affected the cell cycle of Wharton's jelly umbilical cord stem cells [10].…”