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Journal of Bone and Mineral Metabolism
Erschienen in:

27.01.2022 | Original Article

Histone methyltransferase EZH2 in proliferation, invasion, and migration of fibroblast-like synoviocytes in rheumatoid arthritis

verfasst von: Lihua Chang, Renyi Zhou

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 2/2022

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Abstract

Objective

Rheumatoid arthritis (RA) may lead to irreversible joint damage. The role of histone modifications in RA has been emphasized. This study investigated the effect of histone methyltransferase EZH2 on fibroblast-like synoviocytes (FLSs) in RA.

Materials and methods

Synovial tissues were collected from RA patients and non-RA patients (NC). RA-FLSs and NC-FLSs were isolated and identified using flow cytometry. EZH2 expression in synovial tissues and FLSs was detected using RT-qPCR and Western blot. The proliferation, migration, and invasion of RA-FLSs and NC-FLSs were measured using MTT, EdU, and Transwell assays. The binding of EZH2, H3K27me3, and miR-22-3p was analyzed using ChIP assay. The targeting relationship between miR-22-3p and CYR61 was verified using dual-luciferase assay. miR-22-3p and CYR61 expressions were detected using RT-qPCR. CYR61 and H3K27me3 levels were detected using Western blot. Functional rescue experiments were performed to verify the effect of miR-22-3p or CYR61 on RA-FLSs.

Results

EZH2 was highly expressed in synovial tissues and FLSs from RA patients. The proliferation, migration, and invasion ability of RA-FLSs was stronger than that of NC-FLSs. Downregulation of EZH2 repressed proliferation, migration, and invasion of RA-FLSs. EZH2 inhibited miR-22-3p expression by binding to the miR-22-3p promoter and increasing H3K27me3 methylation level, and thereby upregulated CYR61 expression. Downregulation of miR-22-3p or overexpression of CYR61 annulled the inhibitory effect of EZH2 silencing on RA-FLS proliferation, migration, and invasion.

Conclusion

EZH2 bound to the miR-22-3p promoter and inhibited miR-22-3p expression by upregulating H3K27me3 level, thereby promoting CYR61 expression and inducing the proliferation, migration, and invasion of RA-FLSs.
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Metadaten
Titel
Histone methyltransferase EZH2 in proliferation, invasion, and migration of fibroblast-like synoviocytes in rheumatoid arthritis
verfasst von
Lihua Chang
Renyi Zhou
Publikationsdatum
27.01.2022
Verlag
Springer Singapore
Erschienen in
Journal of Bone and Mineral Metabolism / Ausgabe 2/2022
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-021-01299-y

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