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Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis

Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SFs) play a major role in cartilage and bone destruction through tumor−like proliferation, migration, and invasion. Circular RNAs (circRNAs) have emerged as vital regulators for tumor progression. However, the re...

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Autores principales: Xu, Yayun, Zai, Zhuoyan, Lu, Zheng, Zhang, Tao, Wang, Longfei, Qian, Xuewen, Tao, Jingjing, Peng, Xiaoqing, Zhang, Yihao, Chen, Feihu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051600/
https://www.ncbi.nlm.nih.gov/pubmed/36982956
http://dx.doi.org/10.3390/ijms24065880
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author Xu, Yayun
Zai, Zhuoyan
Lu, Zheng
Zhang, Tao
Wang, Longfei
Qian, Xuewen
Tao, Jingjing
Peng, Xiaoqing
Zhang, Yihao
Chen, Feihu
author_facet Xu, Yayun
Zai, Zhuoyan
Lu, Zheng
Zhang, Tao
Wang, Longfei
Qian, Xuewen
Tao, Jingjing
Peng, Xiaoqing
Zhang, Yihao
Chen, Feihu
author_sort Xu, Yayun
collection PubMed
description Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SFs) play a major role in cartilage and bone destruction through tumor−like proliferation, migration, and invasion. Circular RNAs (circRNAs) have emerged as vital regulators for tumor progression. However, the regulatory role, clinical significance, and underlying mechanisms of circRNAs in RASF tumor−like growth and metastasis remain largely unknown. Differentially expressed circRNAs in synovium samples from patients with RA and patients with joint trauma were identified via RNA sequencing. Subsequently, in vitro and in vivo experiments were performed to investigate the functional roles of circCDKN2B−AS_006 in RASF proliferation, migration, and invasion. CircCDKN2B−AS_006 was upregulated in synovium samples from patients with RA and promoted the tumor-like proliferation, migration, and invasion of RASFs. Mechanistically, circCDKN2B−AS_006 was shown to regulate the expression of runt−related transcription factor 1 (RUNX1) by sponging miR-1258, influencing the Wnt/β−catenin signaling pathway, and promoting the epithelial−to−mesenchymal transition (EMT) in RASFs. Moreover, in the collagen−induced arthritis (CIA) mouse model, intra−articular injection of lentivirus−shcircCDKN2B−AS_006 was capable of alleviating the severity of arthritis and inhibiting the aggressive behaviors of SFs. Furthermore, the correlation analysis results revealed that the circCDKN2B−AS_006/miR−1258/RUNX1 axis in the synovium was correlated with the clinical indicators of RA patients. CircCDKN2B−AS_006 promoted the proliferation, migration, and invasion of RASFs by modulating the miR−1258/RUNX1 axis.
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spelling pubmed-100516002023-03-30 Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis Xu, Yayun Zai, Zhuoyan Lu, Zheng Zhang, Tao Wang, Longfei Qian, Xuewen Tao, Jingjing Peng, Xiaoqing Zhang, Yihao Chen, Feihu Int J Mol Sci Article Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SFs) play a major role in cartilage and bone destruction through tumor−like proliferation, migration, and invasion. Circular RNAs (circRNAs) have emerged as vital regulators for tumor progression. However, the regulatory role, clinical significance, and underlying mechanisms of circRNAs in RASF tumor−like growth and metastasis remain largely unknown. Differentially expressed circRNAs in synovium samples from patients with RA and patients with joint trauma were identified via RNA sequencing. Subsequently, in vitro and in vivo experiments were performed to investigate the functional roles of circCDKN2B−AS_006 in RASF proliferation, migration, and invasion. CircCDKN2B−AS_006 was upregulated in synovium samples from patients with RA and promoted the tumor-like proliferation, migration, and invasion of RASFs. Mechanistically, circCDKN2B−AS_006 was shown to regulate the expression of runt−related transcription factor 1 (RUNX1) by sponging miR-1258, influencing the Wnt/β−catenin signaling pathway, and promoting the epithelial−to−mesenchymal transition (EMT) in RASFs. Moreover, in the collagen−induced arthritis (CIA) mouse model, intra−articular injection of lentivirus−shcircCDKN2B−AS_006 was capable of alleviating the severity of arthritis and inhibiting the aggressive behaviors of SFs. Furthermore, the correlation analysis results revealed that the circCDKN2B−AS_006/miR−1258/RUNX1 axis in the synovium was correlated with the clinical indicators of RA patients. CircCDKN2B−AS_006 promoted the proliferation, migration, and invasion of RASFs by modulating the miR−1258/RUNX1 axis. MDPI 2023-03-20 /pmc/articles/PMC10051600/ /pubmed/36982956 http://dx.doi.org/10.3390/ijms24065880 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Yayun
Zai, Zhuoyan
Lu, Zheng
Zhang, Tao
Wang, Longfei
Qian, Xuewen
Tao, Jingjing
Peng, Xiaoqing
Zhang, Yihao
Chen, Feihu
Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis
title Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis
title_full Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis
title_fullStr Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis
title_full_unstemmed Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis
title_short Circular RNA CircCDKN2B−AS_006 Promotes the Tumor-like Growth and Metastasis of Rheumatoid Arthritis Synovial Fibroblasts by Targeting the miR−1258/RUNX1 Axis
title_sort circular rna circcdkn2b−as_006 promotes the tumor-like growth and metastasis of rheumatoid arthritis synovial fibroblasts by targeting the mir−1258/runx1 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051600/
https://www.ncbi.nlm.nih.gov/pubmed/36982956
http://dx.doi.org/10.3390/ijms24065880
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