Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis

Circular RNAs (circRNAs) have emerged as important roles in various inflammatory processes of rheumatic diseases. However, their expression profiles and influences in the pathogenesis of ankylosing spondylitis (AS) remain unclear. In this study, we revealed the differential expression profiles of ci...

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Main Authors: Minkai Song, Jiawen Gao, Tao Yan, Enguang Bi, Taixue An, Xiangyu Wang, Weizhou Jiang, Ting Wang, Zishuo Chen, Zhanjun Shi, Chao Zhang, Jun Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.737599/full
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author Minkai Song
Jiawen Gao
Tao Yan
Enguang Bi
Taixue An
Xiangyu Wang
Weizhou Jiang
Ting Wang
Zishuo Chen
Zhanjun Shi
Chao Zhang
Jun Xiao
author_facet Minkai Song
Jiawen Gao
Tao Yan
Enguang Bi
Taixue An
Xiangyu Wang
Weizhou Jiang
Ting Wang
Zishuo Chen
Zhanjun Shi
Chao Zhang
Jun Xiao
author_sort Minkai Song
collection DOAJ
description Circular RNAs (circRNAs) have emerged as important roles in various inflammatory processes of rheumatic diseases. However, their expression profiles and influences in the pathogenesis of ankylosing spondylitis (AS) remain unclear. In this study, we revealed the differential expression profiles of circRNAs in peripheral blood mononuclear cells (PBMCs) in AS by circRNA sequencing. We screened the differentially expressed circRNAs in AS and verified that hsa_circ_0000652 was upregulated and had potential to be a biomarker of progression. Functionally, hsa_circ_0000652 promoted proliferation and cytokine production in macrophages and inhibited apoptosis. Through dual-luciferase assays and RNA pull-down assays, we demonstrated that hsa_circ_0000652 acted as a competing endogenous RNA (ceRNA) by binding with hsa-miR-1179 and regulated OX40L, which is characterized as a co-stimulatory molecule and found to be upregulated in AS patients. As a result, hsa_circ_0000652 aggravated the inflammation in the coculture system containing CD4+ T cells and macrophages via OX40/OX40L interaction. Our findings suggest that hsa_circ_0000652 was upregulated in AS patients and may serve as a pro-inflammatory factor in macrophages and a positive regulator of OX40/OX40L by sponging hsa-miR-1179.
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spelling doaj.art-23921666659242f48cf7f61796cb017c2022-12-21T17:44:38ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-12-01910.3389/fcell.2021.737599737599Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing SpondylitisMinkai Song0Jiawen Gao1Tao Yan2Enguang Bi3Taixue An4Xiangyu Wang5Weizhou Jiang6Ting Wang7Zishuo Chen8Zhanjun Shi9Chao Zhang10Jun Xiao11Division of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDivision of Spinal Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDivision of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Laboratory Medicine, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Endocrinology and Metabolism, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDivision of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDivision of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Southern Medical University, Guangzhou, ChinaDivision of Orthopaedic Surgery, Department of Orthopaedics, NanFang Hospital, Southern Medical University, Guangzhou, ChinaCircular RNAs (circRNAs) have emerged as important roles in various inflammatory processes of rheumatic diseases. However, their expression profiles and influences in the pathogenesis of ankylosing spondylitis (AS) remain unclear. In this study, we revealed the differential expression profiles of circRNAs in peripheral blood mononuclear cells (PBMCs) in AS by circRNA sequencing. We screened the differentially expressed circRNAs in AS and verified that hsa_circ_0000652 was upregulated and had potential to be a biomarker of progression. Functionally, hsa_circ_0000652 promoted proliferation and cytokine production in macrophages and inhibited apoptosis. Through dual-luciferase assays and RNA pull-down assays, we demonstrated that hsa_circ_0000652 acted as a competing endogenous RNA (ceRNA) by binding with hsa-miR-1179 and regulated OX40L, which is characterized as a co-stimulatory molecule and found to be upregulated in AS patients. As a result, hsa_circ_0000652 aggravated the inflammation in the coculture system containing CD4+ T cells and macrophages via OX40/OX40L interaction. Our findings suggest that hsa_circ_0000652 was upregulated in AS patients and may serve as a pro-inflammatory factor in macrophages and a positive regulator of OX40/OX40L by sponging hsa-miR-1179.https://www.frontiersin.org/articles/10.3389/fcell.2021.737599/fullcircular RNAcompeting endogenous RNAankylosing spondylitismacrophage activationco-stimulatory molecules
spellingShingle Minkai Song
Jiawen Gao
Tao Yan
Enguang Bi
Taixue An
Xiangyu Wang
Weizhou Jiang
Ting Wang
Zishuo Chen
Zhanjun Shi
Chao Zhang
Jun Xiao
Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis
Frontiers in Cell and Developmental Biology
circular RNA
competing endogenous RNA
ankylosing spondylitis
macrophage activation
co-stimulatory molecules
title Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis
title_full Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis
title_fullStr Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis
title_full_unstemmed Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis
title_short Hsa_circ_0000652 Aggravates Inflammation by Activation of Macrophages and Enhancement of OX40/OX40L Interaction in Ankylosing Spondylitis
title_sort hsa circ 0000652 aggravates inflammation by activation of macrophages and enhancement of ox40 ox40l interaction in ankylosing spondylitis
topic circular RNA
competing endogenous RNA
ankylosing spondylitis
macrophage activation
co-stimulatory molecules
url https://www.frontiersin.org/articles/10.3389/fcell.2021.737599/full
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