MicroRNA‐543 functions as an osteogenesis promoter in human periodontal ligament‐derived stem cells by inhibiting transducer of ERBB2, 2

Abstract

Background and Objective Previous research has indicated that altered expression of microRNAs (miRNAs) is in connection with osteogenesis of human periodontal ligament‐derived stem cells (hPDLSCs). We investigated the mechanisms by which miR‐543 promotes osteogenic differentiation of hPDLSCs. Material and Methods First, the expression of miR‐543 in hPDLSCs cultured with or without an osteogenic inductive cocktail was explored. Then, the function of miR‐543 during osteogenesis of hPDLSCs was investigated by overexpressing and inhibiting miR‐543. Next, 3 databases were used to predict target genes of miR‐543 and a luciferase report was used to validate the direct regulation of miR‐543 on the target gene. Further, a rescue experiment using co‐transfection of miR‐543 mimic and target mimic was performed to evaluate whether overexpressing the target gene could partly rescue the efficiency of overexpressing miR‐543 on osteogenesis in hPDLSCs. Results miR‐543 was upregulated during osteogenic differentiation of hPDLSCs. Functional experiments showed that overexpressing miR‐543 could enhance osteogenesis, while inhibiting miR‐543 resulted in reduced formation of mineralized nodules. The transducer of ERBB2, 2 (TOB2) was identified as a target gene of miR‐543 and luciferase report revealed that miR‐543 interacts directly with the 3′‐untranslated repeat sequence of TOB2 mRNA. Overexpression of miR‐543 inhibited the expression of TOB2 in both mRNA and protein levels while inhibiting miR‐543 increased. Furthermore, the rescue experiment confirmed the promotional role of miR‐543 TOB2 expression could be abrogated by overexpressing TOB2, which also had the effect of reducing osteogenic differentiation. Conclusion Our research confirmed that miR‐543 is a promoter of osteogenesis in hPDLSCs, acting by inhibiting its target gene TOB2, which suggests that miR‐543 may be a potential therapy for bone loss in periodontitis.

Genome-wide identification of long noncoding RNAs and their competing endogenous RNA networks involved in the odontogenic differentiation of human dental pulp stem cells

“…Singlecell suspensions were inoculated into six-well plates at a density of 1 × 10 4 cells/well. Limited dilution techniques were used to obtain colonies of single-cell origin [24].…”

The role of miR‐543 in human cancerous and noncancerous diseases

“…LncRNA LEF1-AS1 Glioblastoma Bing et al (2014) LncRNA THUMPD3-AS1 Non-small-cell lung cancer C. C. Wang et al (2018) LncRNA SNHG10 Non-small-cell lung cancer P. Chen et al (2017) Linc-PINT Non-small-cell lung cancer Clevers (2006) Esophageal cancer Dang et al (2017) LncRNA HCG11 Prostate cancer Du et al (2017) LncRNA PCAT6 Cervical cancer Evert et al (2018) LncRNA PVT1 Rheumatoid arthritis Fan et al (2016) LncRNA SNHG7 Diabetic retinopathy Fuentes-Mattei et al 2020LncRNA RNF7 Cardiac fibrosis Ge et al (2018) LncRNA XIST a Atherosclerosis Guglielmelli et al (2015)…”

Noncoding RNAs: new insights into the odontogenic differentiation of dental tissue-derived mesenchymal stem cells

“…RNA polymerase III Dicer processes pre-miRNAs into mature miRNAs [41]. Studies have shown that mature miRNAs bind with the 3′-UTR of target mRNA completely or incompletely, which influences the stability of mRNAs or inhibits their translation and eventually downregulates protein expression [42][43][44]. In addition to this main mechanism, other unconventional mechanisms are gradually being explored ( Fig.…”