Abstract
Introduction
MicroRNAs have been shown to play a role in the pathogenesis of apical periodontitis.
Upregulation of miR-10a-5p and downregulation of miR-891a-5p were previously reported
in apical periodontitis samples. This study aims to perform a functional characterization
of miR-10a-5p, investigating its capacity to regulate the expression of inflammatory
cytokines and growth factors, as well as a possible co-regulation mechanism with miR-891a-5p
in the development of apical periodontitis.
Methods
miR-10a-5p mimics/controls and miR-891a-5p inhibitors/controls were introduced to
human K-562 cells in the presence or absence of lipopolysaccharide. Total RNA was
extracted from cell lysates, and target genes were examined via quantitative reverse
transcription-polymerase chain reaction. Cell lysates were also subjected to proteomics
analysis. Furthermore, mimics of miR-10a-5p and inhibitors of miR-891a-5p were co-transfected
into K-562 cells. RNA sequencing and quantitative reverse transcription-polymerase
chain reaction were carried out to examine their target genes.
Results
Overexpression of miR-10a-5p led to downregulation of tumor necrosis factor-alpha
and interleukin-1 beta mRNA and upregulation of transforming growth factor-beta 1
(TGFB1) mRNA expression, whereas interleukin 3 and TGF-β1 proteins were upregulated. Simultaneous
overexpression of miR-10a-5p and inhibition of miR-891a-5p further increased TGFB1 mRNA transcript levels. RNA sequencing revealed that genes co-regulated by miR-10a-5p
and miR-891a-5p may be involved in apical periodontitis-related pathways such as tumor
necrosis factor, transient receptor potential, and vascular endothelial growth factor
signaling pathways.
Conclusions
miR-10a-5p may modulate the expression of multiple inflammatory cytokines and growth
factors such as tumor necrosis factor-alpha, IL-1β, interleukin 3, and TGF-β1. In
addition, miR-10a-5p and miR-891a-5p cooperatively regulate TGFB1 gene expression, and the gene network of this co-regulation is integrated with many
pathways in apical periodontitis.
Key Words
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Article info
Publication history
Published online: January 07, 2023
Identification
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© 2023 American Association of Endodontists.
