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CircPOMT1 and circMCM3AP inhibit osteogenic differentiation of human adipose-derived stem cells by targeting miR-6881-3p.

ABSTRACT: Circular RNAs (circRNAs), novel endogenous non-coding RNAs with the special circular structure, have been found to play critical roles in various development of tissues and diseases. However, few studies have focused on the functions and mechanisms of circRNAs in the osteogenesis of human adipose-derived stem cells (hASCs). Here, we performed the circRNAs sequencing and bioinformatic analysis to investigate the expression profiles of hASCs during osteogenic differentiation. There were 150 upregulated circRNAs and 60 downregulated circRNAs expressed differentially. Among them, the expression of circPOMT1 and circMCM3AP were downregulated during the osteogenesis of hASCs. hsa-miR-6881-3p could promote the osteogenic differentiation of hASCs, while the expression of circPOMT1 and circMCM3AP were negatively correlated with it. Smad6 and Chordin, critical inhibitors of the BMPs signaling pathway, were predicted to be the targets of hsa-miR-6881-3p. Therefore, circPOMT1 and circMCM3AP might influence the osteogenic differentiation of hASCs by targeting hsa-miR-6881-3p via BMPs signaling pathway. CircPOMT1 and circMCM3AP are potential novel targets for the repairment of bone defects.

SUBMITTER: Huang XQ

PROVIDER: S-EPMC6731423 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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CircPOMT1 and circMCM3AP inhibit osteogenic differentiation of human adipose-derived stem cells by targeting miR-6881-3p.

Huang Xin-Qi XQ Cen Xiao X Sun Wen-Tian WT Xia Kai K Yu Li-Yuan LY Liu Jun J Zhao Zhi-He ZH

American journal of translational research 20190815 8

Circular RNAs (circRNAs), novel endogenous non-coding RNAs with the special circular structure, have been found to play critical roles in various development of tissues and diseases. However, few studies have focused on the functions and mechanisms of circRNAs in the osteogenesis of human adipose-derived stem cells (hASCs). Here, we performed the circRNAs sequencing and bioinformatic analysis to investigate the expression profiles of hASCs during osteogenic differentiation. There were 150 upregu ...[more]

PMID: 31497198

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Project description:BackgroundAn increasing number of studies have shown that dysregulated miR-589-3p is associated with multiple diseases. However, the role of miR-589-3p in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. This study aimed to explore the biological function and potential molecular mechanism of miR-589-3p in osteogenic differentiation of PDLSCs.MethodsGSE159508 was downloaded from Gene Expression Omibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ). Differentially expressed miRNAs between osteogenic induction PDLSCs versus non-induction PDLSCs were obtained by R software. miR-589-3p mimic and miR-589-3p inhibitor and corresponding negative control were obtained and to identify the role of miR-589-3p in osteogenic differentiation of PDLSCs. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. The targeted binding relationship between miR-589-3p and ATF1 was predicted and verified by target prediction analysis and dual-luciferase assay. Furthermore, the functional mechanism based on miR-589-3p and ATF1 in osteogenic differentiation of PDLSCs was further investigated through rescue experiments.ResultsAccording to the cut-off criteria with log 2 FC > 1.0 and P < 0.05, 514 differentially expressed miRNAs were identified between osteogenic induction and non-induction PDLSCs, including 309 upregulated miRNAs and 205 downregulated miRNAs. Compared with control PDLSCs, miR-589-3p expression level was notably increased in PDLSCs that underwent osteogenic induction. The overexpression of miR-589-3p promoted the cell viability of PDLSCs, while the low expression of miR-589-3p had the opposite effect. The dual luciferase reporter assay verified that ATF1 was proved to be a direct target of miR-589-3p in PDLSCs. And overexpressed miR-589-3p reduced the expression of ATF1. Overexpression of miR-589-3p enhanced the osteogenic capacity of PDLSCs, as demonstrated by increases in ALP activity, matrix mineralization, and RUNX2, OCN and OSX expression. In addition, the rescue experiments confirmed that overexpressed ATF1 restored the effects of overexpressed miR-589-3p on cell proliferation and osteogenic differentiation of PDLSCs.ConclusionmiR-589-3p could down-regulate the expression of ATF1, thereby promote the proliferation and osteogenic differentiation of PDLSCs. This finding may provide a new therapeutic target for molecular therapy of periodontitis.

Dataset Information

CircPOMT1 and circMCM3AP inhibit osteogenic differentiation of human adipose-derived stem cells by targeting miR-6881-3p.

Publications

CircPOMT1 and circMCM3AP inhibit osteogenic differentiation of human adipose-derived stem cells by targeting miR-6881-3p.

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