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Wen S, Santander J, Barria D, Salazar LA, Sandoval C, Arias C, Iturriaga V. Epigenetic Biomarkers in Temporomandibular Joint Osteoarthritis: An Emerging Target in Treatment. Int J Mol Sci 2025; 26:3668. [PMID: 40332184 PMCID: PMC12027526 DOI: 10.3390/ijms26083668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/07/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025] Open
Abstract
Osteoarthritis (OA) of the temporomandibular joint (TMJ) is a progressive disease characterized by the progressive destruction of the internal surfaces of the joint. Certain epigenetic biomarkers have been detected in TMJ-OA. We summarized the available evidence on the epigenetic biomarkers in TMJ-OA. There is an increase in the expression of non-coding RNAs related to the degradation of the extracellular matrix, chondrocyte apoptosis, and proinflammatory cytokines, while there is a decrease in the expression of those related to COL2A1, as well as the osteogenic and chondrogenic differentiation of mesenchymal stem cells. Certain methylated genes and histone modifications in TMJ-OA were also identified. In the early stage, DNA methylation was significantly decreased; that is, the expression of inflammation-related genes such as TNF and genes associated with extracellular matrix degradation, such as Adamts, were increased. While in the late stage, there was an increase in the expression of genes associated with the TGF-β and MAPK signaling pathway and angiogenesis-related genes. Although research on the role of epigenetic markers in TMJ-OA is still ongoing, the results here contribute to improving the basis for the identification of accurate diagnostic and prognostic markers and the development of new therapeutic molecules for the prevention and management of TMJ-OA. It also represents a significant advancement in elucidating its pathogenesis.
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Affiliation(s)
- Schilin Wen
- Grupo de Investigación de Pregrado en Odontología, Universidad Autónoma de Chile, Temuco 4811230, Chile; (S.W.); (J.S.); (D.B.)
- Sleep & Pain Research Group, Faculty of Dentistry, Universidad de La Frontera, Temuco 4811230, Chile
| | - Javiera Santander
- Grupo de Investigación de Pregrado en Odontología, Universidad Autónoma de Chile, Temuco 4811230, Chile; (S.W.); (J.S.); (D.B.)
| | - Daniel Barria
- Grupo de Investigación de Pregrado en Odontología, Universidad Autónoma de Chile, Temuco 4811230, Chile; (S.W.); (J.S.); (D.B.)
| | - Luis A. Salazar
- Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco 4811230, Chile;
| | - Cristian Sandoval
- Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Los Carreras 753, Osorno 5310431, Chile
- Departamento de Medicina Interna, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile
| | - Consuelo Arias
- Escuela de Medicina, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 8580745, Chile;
| | - Verónica Iturriaga
- Sleep & Pain Research Group, Faculty of Dentistry, Universidad de La Frontera, Temuco 4811230, Chile
- Department of Integral Adult Care Dentistry, Temporomandibular Disorder and Orofacial Pain Program, Universidad de La Frontera, Temuco 4811230, Chile
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Wang Y, Chen X, Chen Y, Sun Q, Wang H. Regulatory effect and mechanism of CircSEC24A in IL-1β-induced osteoarthritis. Arch Physiol Biochem 2025; 131:188-198. [PMID: 39328069 DOI: 10.1080/13813455.2024.2404975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 06/27/2024] [Accepted: 09/09/2024] [Indexed: 09/28/2024]
Abstract
Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_0128006 (also known as circSEC24) was reported as an upregulated circRNA in OA tissues, but its biological role and underlying mechanism in OA are still to be discussed. circSEC24A and NAMPT expression levels were upregulated, and miR-515-5p was reduced in OA cartilage tissues and IL-1β-treated CHON-001 cells. The absence of circSEC24A overturned IL-1β-induced suppression of cell viability and promotion of oxidative stress, apoptosis, extracellular matrix (ECM) degradation, and inflammation in CHON-001 cells. Mechanistically, circSEC24A acted as a molecular sponge for miR-515-5p to affect NAMPT expression. CircSEC24A knockdown could attenuate IL-1β-triggered CHON-001 cell injury partly via the miR-515-5p/NAMPT axis, providing new insight into the underlying application of circSEC24A in OA treatment.
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Affiliation(s)
- Yuanrui Wang
- Department of Orthopaedics, Xijing Hospital, The Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Xiaochao Chen
- Department of Orthopaedics, Xijing Hospital, The Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Yongfeng Chen
- Department of Orthopaedics, Xijing Hospital, The Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Qiang Sun
- Department of Orthopaedics, Xijing Hospital, The Air Force Military Medical University, Xi'an, Shaanxi, China
| | - Huayi Wang
- Department of Orthopaedics, Xijing Hospital, The Air Force Military Medical University, Xi'an, Shaanxi, China
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Wang C, Yang D, Zhu Y, Yang Q, Liu T, Liu X, Zhao D, Bao X, Dong T, Shao L, Tang L. Circulating circular RNAs act as potential novel biomarkers for sepsis secondary to pneumonia: a prospective cohort study. World J Emerg Med 2025; 16:144-152. [PMID: 40135204 PMCID: PMC11930550 DOI: 10.5847/wjem.j.1920-8642.2025.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 12/09/2024] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Circulating biomarkers for sepsis are lacking, and research on circular RNAs (circRNAs) as potential biomarkers of pneumonia-induced sepsis is limited. This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis. METHODS This prospective cohort study included 40 healthy individuals, 60 patients with pneumonia, and 80 patients with pneumonia-induced sepsis. CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman correlation analysis was used to evaluate the associations between circRNAs, inflammatory markers, Sequential Organ Failure Assessment (SOFA) scores, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Receiver operating characteristic (ROC) curves analysis were used to assess the diagnostic performance of circRNAs, while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality. RESULTS qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients. Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores, whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters. The area under the curve (AUC) values for Circ-CTD-2281E23.2, Circ-0075723, and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728, 0.706, and 0.793, respectively. The combination of these circRNAs (AUC=0.846) and the combination with other clinical indicators (AUC=0.990) demostrated enhanced AUC values. The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765, respectively. CONCLUSION This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis. Circ-CTD-2281E23.2, Circ-0075723, and Circ-0008679 exhibit diagnostic potential, with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.
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Affiliation(s)
- Chunxue Wang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Dianyin Yang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Yuxin Zhu
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Qian Yang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Tong Liu
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Xiandong Liu
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Dongyang Zhao
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Xiaowei Bao
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Tiancao Dong
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
| | - Li Shao
- Department of VIP Clinic, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Lunxian Tang
- Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200120, China
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Shakeri M, Aminian A, Mokhtari K, Bahaeddini M, Tabrizian P, Farahani N, Nabavi N, Hashemi M. Unraveling the molecular landscape of osteoarthritis: A comprehensive review focused on the role of non-coding RNAs. Pathol Res Pract 2024; 260:155446. [PMID: 39004001 DOI: 10.1016/j.prp.2024.155446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 06/27/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024]
Abstract
Osteoarthritis (OA) poses a significant global health challenge, with its prevalence anticipated to increase in the coming years. This review delves into the emerging molecular biomarkers in OA pathology, focusing on the roles of various molecules such as metabolites, noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Advances in omics technologies have transformed biomarker identification, enabling comprehensive analyses of the complex pathways involved in OA pathogenesis. Notably, ncRNAs, especially miRNAs and lncRNAs, exhibit dysregulated expression patterns in OA, presenting promising opportunities for diagnosis and therapy. Additionally, the intricate interplay between epigenetic modifications and OA progression highlights the regulatory role of epigenetics in gene expression dynamics. Genome-wide association studies have pinpointed key genes undergoing epigenetic changes, providing insights into the inflammatory processes and chondrocyte hypertrophy typical of OA. Understanding the molecular landscape of OA, including biomarkers and epigenetic mechanisms, holds significant potential for developing innovative diagnostic tools and therapeutic strategies for OA management.
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Affiliation(s)
- Mohammadreza Shakeri
- MD, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Aminian
- MD, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Khatere Mokhtari
- Department of Cellular and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Mohammadreza Bahaeddini
- MD, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Pouria Tabrizian
- MD, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Najma Farahani
- Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Noushin Nabavi
- Independent Researcher, Victoria, British Columbia V8V 1P7, Canada
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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Dadihanc T, Zhang Y, Li GQ, Zhou HK, Huang J, Zhang X, Li ZQ, Ma HR. CircRNA SEC24A promotes osteoarthritis through miR-107-5p/CASP3 axis. Regen Ther 2024; 26:60-70. [PMID: 38828010 PMCID: PMC11143789 DOI: 10.1016/j.reth.2024.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/08/2024] [Accepted: 04/25/2024] [Indexed: 06/05/2024] Open
Abstract
Background Osteoarthritis (OA) is the most frequently diagnosed chronic joint disease. CircSEC24A is significantly elevated in OA chondrocytes upon IL-1β stimulation. However, its biological function in OA is still not fully understood. Methods The circRNAs-miRNA-mRNA network was predicted by bioinformatics analysis. An in vitro OA chondrocytes model was established by IL-1β stimulation. The expression of circSEC24A, miR-107-5p, CASP3, apoptosis-related molecules and extracellular matrix (ECM) components were detected by Western blot and qRT-PCR. MTT assay and Annexin V/PI staining were employed to monitor cell viability and apoptosis, respectively. The interaction between circSEC24A and miR-107-5p, as well as the binding between miR-107-5p and CASP3 3' UTR were detected by luciferase reporter and RIP assays. Cytokine secretion was monitored by ELISA assay. The role of circSEC24A was also explored in anterior cruciate ligament transection (ACLT) rat models. Results CircSEC24A and CASP3 were increased, but miR-107-5p was decreased in rat OA cartilage tissues and OA chondrocytes. CircSEC24A acted as a sponge of miR-107-5p. Knockdown of circSEC24A promoted chondrocyte proliferation, but suppressed chondrocyte apoptosis, ECM degradation and inflammation via sponging miR-107-5p. CASP3 was identified as a miR-107-5p target gene. MiR-107-5p mimics protected against OA progression via targeting CASP3. Silencing of circSEC24A alleviated OA progression in ACLT model. Conclusion CircSEC24A promotes OA progression through miR-107-5p/CASP3 axis.
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Affiliation(s)
- Tuerxunjiang Dadihanc
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
- Department of Orthopaedic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
| | - Yong Zhang
- School of Life Science and Technology, Shanghai Jiao Tong University, Shanghai 200010, PR China
| | - Guo-Qing Li
- Department of Orthopaedic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
| | - Hai-Kang Zhou
- Department of Orthopaedic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
| | - Jingyong Huang
- Department of Orthopaedic Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
| | - Xue Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
| | - Zhi-Qiang Li
- Animal Research Center, Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
| | - Hai-Rong Ma
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medicine Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Province, PR China
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Yue Y, Dai W, Wei Y, Cao S, Liao S, Li A, Liu P, Lin J, Zeng H. Unlocking the potential of exosomes: a breakthrough in the theranosis of degenerative orthopaedic diseases. Front Bioeng Biotechnol 2024; 12:1377142. [PMID: 38699435 PMCID: PMC11064847 DOI: 10.3389/fbioe.2024.1377142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 04/01/2024] [Indexed: 05/05/2024] Open
Abstract
Degenerative orthopaedic diseases pose a notable worldwide public health issue attributable to the global aging population. Conventional medical approaches, encompassing physical therapy, pharmaceutical interventions, and surgical methods, face obstacles in halting or reversing the degenerative process. In recent times, exosome-based therapy has gained widespread acceptance and popularity as an effective treatment for degenerative orthopaedic diseases. This therapeutic approach holds the potential for "cell-free" tissue regeneration. Exosomes, membranous vesicles resulting from the fusion of intracellular multivesicles with the cell membrane, are released into the extracellular matrix. Addressing challenges such as the rapid elimination of natural exosomes in vivo and the limitation of drug concentration can be effectively achieved through various strategies, including engineering modification, gene overexpression modification, and biomaterial binding. This review provides a concise overview of the source, classification, and preparation methods of exosomes, followed by an in-depth analysis of their functions and potential applications. Furthermore, the review explores various strategies for utilizing exosomes in the treatment of degenerative orthopaedic diseases, encompassing engineering modification, gene overexpression, and biomaterial binding. The primary objective is to provide a fresh viewpoint on the utilization of exosomes in addressing bone degenerative conditions and to support the practical application of exosomes in the theranosis of degenerative orthopaedic diseases.
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Affiliation(s)
- Yaohang Yue
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Wei Dai
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Yihao Wei
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Siyang Cao
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Shuai Liao
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Aikang Li
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Peng Liu
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Jianjing Lin
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Sports Medicine and Rehabilitation, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Hui Zeng
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
- Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- National and Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Shenzhen Second People’s Hospital, Shenzhen, Guangdong, China
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Tan J, Sahaer P, Li H, Han W, Sun H. The expression, function, and network regulation of circDNAJB6 in chicken macrophages under lipopolysaccharide (LPS) stimulation. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2024; 151:105095. [PMID: 37951323 DOI: 10.1016/j.dci.2023.105095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 10/06/2023] [Accepted: 11/06/2023] [Indexed: 11/13/2023]
Abstract
Circular RNAs (circRNA) originate from back-splicing events that link a downstream 5'splice site to an upstream 3' splice site. Circular RNA has been shown to be involved in gene expression, interacting with microRNA and RNA binding proteins to affect transcription, splicing, translation, and other processes. However, little is known about the potential function of chicken circRNAs that trigger the pathogenesis. In a previous study, a circular RNA DNAJB6 (circDNAJB6) was identified as a typical covalently closed circular RNA that is abundant in chicken macrophages upon bacterial infection. It was identified that circDNAJB6 was formed by reverse splicing of exons 2 to 5 of the DNAJB6 gene by PCR amplification, Sanger sequencing, and RNase R exonuclease treatment. Moreover, circDNAJB6 had ability to exacerbate the lipopolysaccharides (LPS) induced cellular injury via reducing cell viability, increasing NO product and pro-inflammatory cytokines. In addition, bioinformatic analysis showed that five miRNAs were identified to interact with circDNAJB6, potentially targeting 75 genes, which were significantly enriched in the pathways of autophagy-animal and MAPK signaling. This study has provided and broadened a better understanding the function of circDNAJB6, which may exert potential biomarkers and act as potential targets for the treatment of bacterial infection.
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Affiliation(s)
- Jishuang Tan
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Paizelaiti Sahaer
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Huan Li
- School of Biological and Chemical Engineering, Yangzhou Polytechnic College, Yangzhou, China
| | - Wei Han
- The Poultry Research Institute of Chinese Academy of Agricultural Sciences, Yangzhou, China
| | - Hongyan Sun
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture & Agri-Product Safety, Ministry of Education, Yangzhou University, Yangzhou, China.
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Liang S, Liu S, Song J, Lin Q, Zhao S, Li S, Li J, Liang S, Wang J. HMCDA: a novel method based on the heterogeneous graph neural network and metapath for circRNA-disease associations prediction. BMC Bioinformatics 2023; 24:335. [PMID: 37697297 PMCID: PMC10494331 DOI: 10.1186/s12859-023-05441-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 08/08/2023] [Indexed: 09/13/2023] Open
Abstract
Circular RNA (CircRNA) is a type of non-coding RNAs in which both ends are covalently linked. Researchers have demonstrated that many circRNAs can act as biomarkers of diseases. However, traditional experimental methods for circRNA-disease associations identification are labor-intensive. In this work, we propose a novel method based on the heterogeneous graph neural network and metapaths for circRNA-disease associations prediction termed as HMCDA. First, a heterogeneous graph consisting of circRNA-disease associations, circRNA-miRNA associations, miRNA-disease associations and disease-disease associations are constructed. Then, six metapaths are defined and generated according to the biomedical pathways. Afterwards, the entity content transformation, intra-metapath and inter-metapath aggregation are implemented to learn the embeddings of circRNA and disease entities. Finally, the learned embeddings are used to predict novel circRNA-disase associations. In particular, the result of extensive experiments demonstrates that HMCDA outperforms four state-of-the-art models in fivefold cross validation. In addition, our case study indicates that HMCDA has the ability to identify novel circRNA-disease associations.
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Affiliation(s)
- Shiyang Liang
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China
- Department of Internal Medicine, The No. 944 Hospital of Joint Logistic Support Force of PLA, Xiongguan Road, Jiuquan, China
| | - Siwei Liu
- Department of Machine Learning, Mohamed bin Zayed University of Artificial Intelligence, Abu Dhabi, United Arab Emirates
| | - Junliang Song
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China
| | - Qiang Lin
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China
| | - Shihong Zhao
- Department of Respiratory Medicine, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China
| | - Shuaixin Li
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China
| | - Jiahui Li
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China
| | - Shangsong Liang
- Department of Machine Learning, Mohamed bin Zayed University of Artificial Intelligence, Abu Dhabi, United Arab Emirates
| | - Jingjie Wang
- Department of Gastroenterology, Tangdu Hospital, Air Force Medical University, Xinsi Road, Xi'an, China.
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Malviya A, Bhuyan R. The recent advancements in circRNA research: From biogenesis to therapeutic interventions. Pathol Res Pract 2023; 248:154697. [PMID: 37506629 DOI: 10.1016/j.prp.2023.154697] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/14/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023]
Abstract
Circular RNAs (circRNAs) belong to the genre of long non-coding RNAs that are formed by special back-splicing events and are currently the molecule of interest for studies globally due their involvement in various ailments like diabetes, neurodegenerative disorders, cardio-vascular diseases and cancers. These class of highly stable RNAs participate in diverse cellular functionalities including microRNA (miRNA) sponging, ceRNA (competing endogenous RNA) activity or via exhibiting RNA binding protein (RBP) interactions. They are also known to regulate cancer progression both positively and negatively through various biological pathways such as, modulating the cell cycle and apoptotic pathways, epigenetic regulation, and translational and/or transcriptional regulations etc. Given its significance, a variety of computational tools and dedicated databases have been created for the identification, quantification, and differential expression of such RNAs in combination with sequencing approaches. In this review, we provide a comprehensive analysis of the numerous computational tools, pipelines, and online resources developed in recent years for the detection and annotation of circRNAs. We also summarise the most recent findings regarding the characteristics, functions, biological processes, and involvement of circRNAs in diseases. The review emphasises the significance of circRNAs as potential disease biomarkers and new treatment targets.
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Affiliation(s)
- Ayushi Malviya
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Tonk, Rajasthan 304022, India
| | - Rajabrata Bhuyan
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Tonk, Rajasthan 304022, India.
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10
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Qadir J, Wen SY, Yuan H, Yang BB. CircRNAs regulate the crosstalk between inflammation and tumorigenesis: The bilateral association and molecular mechanisms. Mol Ther 2023; 31:1514-1532. [PMID: 36518080 PMCID: PMC10278049 DOI: 10.1016/j.ymthe.2022.12.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/16/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022] Open
Abstract
Inflammation, a hallmark of cancer, has been associated with tumor progression, transition into malignant phenotype and efficacy of the chemotherapeutic agents in cancer. Chronic inflammation provides a favorable environment for tumorigenesis by inducing immunosuppression, whereas acute inflammation prompts tumor suppression by generating anti-tumor immune responses. Inflammatory factors derived from interstitial cells or tumor cells can stimulate cell proliferation and survival by modulating oncogenes and/or tumor suppressors. Recently, a new class of RNAs, i.e., circular RNAs (circRNAs), has been implicated in inflammatory diseases. Although there are reports on circRNAs imparting functions in inflammatory insults, whether these circularized transcripts hold the potential to regulate inflammation-induced cancer or tumor-related inflammation, and modulate the interactions between tumor microenvironment (TME) and the inflammatory stromal/immune cells, awaits further elucidation. Contextually, the current review describes the molecular association between inflammation and cancer, and spotlights the regulatory mechanisms by which circRNAs can moderate TME in response to inflammatory signals/triggers. We also present comprehensive information about the immune cell(s)-specific expression and functions of the circRNAs in TME, modulation of inflammatory signaling pathways to drive tumorigenesis, and their plausible roles in inflammasomes and tumor development. Moreover, the therapeutic potential of these circRNAs in harnessing inflammatory responses in cancer is also discussed.
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Affiliation(s)
- Javeria Qadir
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Shuo-Yang Wen
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Hui Yuan
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | - Burton B Yang
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
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11
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Li Z, Lu J. CircRNAs in osteoarthritis: research status and prospect. Front Genet 2023; 14:1173812. [PMID: 37229197 PMCID: PMC10203419 DOI: 10.3389/fgene.2023.1173812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 04/18/2023] [Indexed: 05/27/2023] Open
Abstract
Osteoarthritis (OA) is the most common joint disease globally, and its progression is irreversible. The mechanism of osteoarthritis is not fully understood. Research on the molecular biological mechanism of OA is deepening, among which epigenetics, especially noncoding RNA, is an emerging hotspot. CircRNA is a unique circular noncoding RNA not degraded by RNase R, so it is a possible clinical target and biomarker. Many studies have found that circRNAs play an essential role in the progression of OA, including extracellular matrix metabolism, autophagy, apoptosis, the proliferation of chondrocytes, inflammation, oxidative stress, cartilage development, and chondrogenic differentiation. Differential expression of circRNAs was also observed in the synovium and subchondral bone in the OA joint. In terms of mechanism, existing studies have mainly found that circRNA adsorbs miRNA through the ceRNA mechanism, and a few studies have found that circRNA can serve as a scaffold for protein reactions. In terms of clinical transformation, circRNAs are considered promising biomarkers, but no large cohort has tested their diagnostic value. Meanwhile, some studies have used circRNAs loaded in extracellular vesicles for OA precision medicine. However, there are still many problems to be solved in the research, such as the role of circRNA in different OA stages or OA subtypes, the construction of animal models of circRNA knockout, and more research on the mechanism of circRNA. In general, circRNAs have a regulatory role in OA and have particular clinical potential, but further studies are needed in the future.
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Affiliation(s)
- Zhuang Li
- School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - Jun Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
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12
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Xue Q, Huang Y, Chang J, Cheng C, Wang Y, Wang X, Miao C. CircRNA-mediated ceRNA mechanism in Osteoarthritis: special emphasis on circRNAs in exosomes and the crosstalk of circRNAs and RNA methylation. Biochem Pharmacol 2023; 212:115580. [PMID: 37148980 DOI: 10.1016/j.bcp.2023.115580] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/24/2023] [Accepted: 04/26/2023] [Indexed: 05/08/2023]
Abstract
Osteoarthritis (OA) is an age-related joint disease with chronic inflammation, progressive articular cartilage destruction and subchondral bone sclerosis. CircRNAs (circRNAs) are a class of non-coding RNA with a circular structure that participate in a series of important pathophysiological processes of OA, especially its ceRNA mechanisms, and play an important role in OA. CircRNAs may be potential biomarkers for the diagnosis and prognosis of OA. Additionally, differentially expressed circRNAs were found in patients with OA, indicating that circRNAs are involved in the pathogenesis of OA. Experiments have shown that the intra-articular injection of modified circRNAs can effectively relieve OA. Exosomal circRNAs and methylated circRNAs also provide new ideas for the treatment of OA. Clarifying the important roles of circRNAs in OA will deepen people's understanding of the pathogenesis of OA. CircRNAs may be developed as new biomarkers or drug targets for the diagnosis of OA and provide new methods for the treatment of OA.
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Affiliation(s)
- Qiuyun Xue
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Yurong Huang
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Jun Chang
- Department of Orthopaedics, the First Affiliated Hospital of Anhui Medical University, Hefei, China; Anhui Public Health Clinical Center, Hefei, China.
| | - Chenglong Cheng
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Yuting Wang
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China
| | - Xiaomei Wang
- Department of Humanistic Nursing, School of Nursing, Anhui University of Chinese Medicine, Hefei, China.
| | - Chenggui Miao
- Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China; Institute of Rheumatism, Anhui University of Chinese Medicine, Hefei, China
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13
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Zhang Z, Huang Y, Guo AY, Yang L. Research progress of circular RNA molecules in aging and age-related diseases. Ageing Res Rev 2023; 87:101913. [PMID: 36934850 DOI: 10.1016/j.arr.2023.101913] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/05/2023] [Accepted: 03/15/2023] [Indexed: 03/19/2023]
Abstract
Circular RNAs (circRNAs) are a class of single-chain endogenous closed circular RNAs that do not have a poly(A) tail at the 3' end and a cap structure at the 5' end and are connected end-to-end by covalent bonds. CircRNAs, which are pervasive, diverse, stable, and conversed, have functions in transcriptional control and protein translation and play vital roles in modulating cell senescence, individual aging, as well as the occurrence and development of age-related diseases. Studies in recent years were reviewed from aspects including the biosynthesis mechanisms, classification, expression, biomedical functions, associations with aging and age-related diseases, and potential clinical applications of circRNAs. It will provide the theoretic basis for exploring the molecular biological mechanisms of aging, using circRNA as the therapeutic target to delay aging, and finding therapeutic strategies to prevent and treat age-related diseases.
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Affiliation(s)
- Zhidan Zhang
- Departments of Infectious Disease, The First Hospital of China Medical University, Shenyang, PR China
| | - Yuling Huang
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, PR China
| | - AYao Guo
- Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, PR China.
| | - Lina Yang
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, PR China.
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14
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Kim M, Rubab A, Chan WC, Chan D. Osteoarthritis year in review: genetics, genomics and epigenetics. Osteoarthritis Cartilage 2023:S1063-4584(23)00725-2. [PMID: 36924918 DOI: 10.1016/j.joca.2023.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 03/08/2023] [Accepted: 03/08/2023] [Indexed: 03/18/2023]
Abstract
This "year in review" provides a summary of the research findings on the topic of genetics, genomics and epigenetics for osteoarthritis (OA) between Mar 2021-Apr 2022. A search routine of the literature in PubMed for the keyword, osteoarthritis, together with topics on genetics, genomics, epigenetics, polymorphism, DNA methylation, noncoding RNA, lncRNA, proteomics, and single cell RNA sequencing, returned key research articles and relevant reviews. Following filtering of duplicates across search routines, 695 unique research articles and 112 reviews were identified. We manually curated these articles and selected 90 as references for this review. However, we were unable to refer to all these articles, and only used selected articles to highlight key outcomes and trends. The trend in genetics is on the meta-analysis of existing cohorts with comparable genetic and phenotype characterisation of OA; in particular, clear definition of endophenotypes to enhance the genetic power. Further, many researchers are realizing the power of big data and multi-omics approaches to gain molecular insights for OA, and this has opened innovative approaches to include transcriptomics and epigenetics data as quantitative trait loci (QTLs). Given that most of the genetic loci for OA are not located within coding regions of genes, implying the impact is likely to be on gene regulation, epigenetics is a hot topic, and there is a surge in studies relating to the role of miRNA and long non-coding RNA on cartilage biology and pathology. The findings are exciting and new insights are provided in this review to summarize a year of research and the road map to capture all new innovations to achieve the desired goal in OA prevention and treatment.
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Affiliation(s)
- Minyeong Kim
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Aqsa Rubab
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Wilson Cw Chan
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Danny Chan
- School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
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15
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Zou YC, Wu J, Zhao C, Luo ZR. Analysis of circular RNA expression profile of pathological bone formation in ankylosing spondylitis. Int J Rheum Dis 2023. [PMID: 36876652 DOI: 10.1111/1756-185x.14638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/09/2023] [Accepted: 02/18/2023] [Indexed: 03/07/2023]
Abstract
OBJECTIVE To screen and analyze the function of specific CircRNAs involved in pathological bone formation in patients with ankylosing spondylitis (AS). METHODS From September 2019 to October 2020, hip capsule tissues obtained from 3 patients with AS developed hip joint fusion and 3 patients with femoral neck fracture (FNF) were obtained. The circular RNA expressions of hip capsule were analyzed by Arraystar CircRNA chip. qRT-PCR analysis wan performed to identify the expression patterns of differentially expression CircRNAs. RESULTS Our findings showed that there were 25 up-regulated and 39 down-regulated differential CircRNAs. Among these CircRNAs, we screened 10 highest up-regulatedCircRNAs and 13 lowest down-regulated CircRNAs (Fold Change≥2,P<0.05). In further verification analysis, hsa_circ_0067103, hsa_circ_0004496, and hsa_circ_0002649, ACTG1 were significantly upregulated, while hsa_circ_0020273, hsa_circ_0005699, and hsa_circ_0048764 were markly downregulated in AS tissue than FNF controls. CONCLUSION The expression of CircRNAs involved of pathological bone formation in AS were significantly different from those of control group. These differentially expressed Circular RNAs may be closely related to the occurrence and development of pathological bone formation in AS.
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Affiliation(s)
- Yu-Cong Zou
- The 5th People's Hospital of Foshan, Foshan, China
| | - Juan Wu
- Department of Rehabilitation, Suining Central Hospital, Suining, China
| | - Chang Zhao
- Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Zi-Rui Luo
- The 5th People's Hospital of Foshan, Foshan, China
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Wang R, Li L, Wang J, Zhao X, Shen J. CircBRMS1L Participates in Lipopolysaccharide-induced Chondrocyte Injury via the TLR4/NF-κB Pathway through Serving as a miR-142-5p Decoy. BIOTECHNOL BIOPROC E 2023. [DOI: 10.1007/s12257-021-0224-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Chen A, Chen Y, Rong X, You X, Wu D, Zhou X, Zeng W, Zhou Z. The application of exosomes in the early diagnosis and treatment of osteoarthritis. Front Pharmacol 2023; 14:1154135. [PMID: 37188263 PMCID: PMC10175594 DOI: 10.3389/fphar.2023.1154135] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 04/11/2023] [Indexed: 05/17/2023] Open
Abstract
With the increase in human lifespan and the aggravation of global aging, the incidence of osteoarthritis (OA) is increasing annually. To better manage and control the progression of OA, prompt diagnosis and treatment for early-stage OA are important. However, a sensitive diagnostic modality and therapy for early OA have not been well developed. The exosome is a class of extracellular vesicles containing bioactive substances, that can be delivered directly from original cells to neighboring cells to modulate cellular activities through intercellular communication. In recent years, exosomes have been considered important in the early diagnosis and treatment of OA. Synovial fluid exosome and its encapsulated substances, e.g., microRNA, lncRNA, and proteins, can not only distinguish OA stages but also prevent the progression of OA by directly targeting cartilage or indirectly modulating the immune microenvironment in the joints. In this mini-review, we include recent studies on the diagnostic and therapeutic modalities of exosomes and hope to provide a new direction for the early diagnosis and treatment of OA disease in the future.
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Affiliation(s)
- Anjing Chen
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
- Department of Scientific Research and Experiment Management, West China Hospital, Sichuan University, Chengdu, China
| | - Yangmengfan Chen
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao Rong
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Xuanhe You
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Diwei Wu
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Xinran Zhou
- West China Biobanks and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Weinan Zeng
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Weinan Zeng, ; Zongke Zhou,
| | - Zongke Zhou
- Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University/Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Weinan Zeng, ; Zongke Zhou,
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Chen X, Chen Q, Zhao C, Lu Z. Hsa_circ_0005050 regulated the progression of oral squamous cell carcinoma via miR-487a-3p/CHSY1 axis. J Dent Sci 2023; 18:282-294. [PMID: 36643258 PMCID: PMC9831796 DOI: 10.1016/j.jds.2022.05.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/18/2022] [Indexed: 02/07/2023] Open
Abstract
Background/purpose Circular RNAs (circRNAs) have been identified as potential functional modulators of the cellular physiology processes. This study aims to learn the potential molecular mechanisms of hsa_circ_0005050 (circ_0005050) in oral squamous cell carcinoma (OSCC). Materials and methods Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to examine the expression of circ_0005050, miR-487a-3p, and chondroitin sulfate synthase 1 (CHSY1). Dual-luciferase reporter system, RNA pull-down, and RNA Immunoprecipitation (RIP) assays were used to determine the binding between miR-487a-3p and circ_0005050 or CHSY1. Colony formation experiment and EdU assay were used to investigate proliferation. Wound-healing and transwell assays were used to detect the migration of cells. The apoptosis rate of OSCC cells was tested by flow cytometry. Protein levels of related factors were determined by Western blot. Tumor xenograft was established to determine the regulatory role of circ_0005050 on tumor growth in vivo, and Ki-67 expression was detected in this xenograft using Immunohistochemical (IHC). Results We implicated that circ_0005050 was apparently upregulated in OSCC tissues cells. In function experiments, repressing of circ_0005050 remarkably retarded OSCC growth in vitro. Furthermore, we conducted dual-luciferase reporter assays and RNA pull-down assays to verify that circ_0005050 sponged miR-487a-3p. Suppression of miR-487a-3p rescued the inhibition of proliferation in SCC15 and SCC25 cells induced by circ_0005050 knockdown. In addition, we found that overexpression of CHSY1 also reversed the inhibitory effect of circ_0005050 silencing on cell proliferation. Moreover, circ_0005050 knockdown inhibited tumor growth in vivo. Conclusion Circ_0005050 acted as an oncogenic factor in OSCC progression through miR-487a-3p/CHSY1 axis.
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Affiliation(s)
- Xubin Chen
- Department of Oral and Maxillofacial Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Qiaojiang Chen
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Chen Zhao
- Department of Oral and Maxillofacial Surgery, Jiangmen Central Hospital, Jiangmen, China
| | - Zhiqi Lu
- Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
- Corresponding author. Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, 570311. China.
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Abstract
Bone is a connective tissue that has important functions in the human body. Cells and the extracellular matrix (ECM) are key components of bone and are closely related to bone-related diseases. However, the outcomes of conventional treatments for bone-related diseases are not promising, and hence it is necessary to elucidate the exact regulatory mechanisms of bone-related diseases and identify novel biomarkers for diagnosis and therapy. Circular RNAs (circRNAs) are single-stranded RNAs that form closed circular structures without a 5' cap or 3' tail and polycyclic adenylate tails. Due to their high stability, circRNAs have the potential to be typical biomarkers. Accumulating evidence suggests that circRNAs are involved in bone-related diseases, including osteoarthritis, osteoporosis, osteosarcoma, multiple myeloma, intervertebral disc degeneration, and rheumatoid arthritis. Herein, we summarize the recent research progress on the characteristics and functions of circRNAs, and highlight the regulatory mechanism of circRNAs in bone-related diseases.
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Affiliation(s)
- Linghui HU
- School of Exercise and Health, Shanghai University of Sport, Shanghai200438, China
| | - Wei WU
- School of Exercise and Health, Shanghai University of Sport, Shanghai200438, China
| | - Jun ZOU
- School of Exercise and Health, Shanghai University of Sport, Shanghai200438, China,Jun ZOU,
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20
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Que W, Liu H, Yang Q. CircPRKCH modulates extracellular matrix formation and metabolism by regulating the miR-145/HGF axis in osteoarthritis. Arthritis Res Ther 2022; 24:216. [PMID: 36068644 PMCID: PMC9447342 DOI: 10.1186/s13075-022-02893-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 08/12/2022] [Indexed: 08/30/2023] Open
Abstract
BACKGROUND Osteoarthritis (OA) is a chronic degenerative joint disease. Extracellular matrix (ECM) degradation is essential for OA progression. Previous studies have shown that circular RNAs (circRNAs) are involved in the pathological process of OA. CircPRKCH has been shown to be upregulated in OA chondrocytes. The present study was aimed to explore the roles of circPRKCH in vivo and in vitro models of OA and its underlying molecular mechanisms. METHODS IL-1β-induced chondrocytes and mice injected with monosodium iodoacetate were used as OA models in vitro and in vivo, respectively. RT-qPCR was performed to measure the expression of circPRKCH, miR-145, and HGF in cartilage tissues and chondrocytes. The interaction between miR-145 and circPRKCH or HGF was verified by a dual-luciferase reporter assay. Chondrocyte apoptosis, viability, and ECM-related proteins were examined by flow cytometry, MTT assay, and Western blotting, respectively. Histopathological changes were detected by HE and Safranin O-fast green staining. RESULTS The expression of circPRKCH and HGF was increased in OA cartilage tissues and IL-1β-treated chondrocytes, while miR-145 expression was decreased. IL-1β induced chondrocyte apoptosis and ECM degradation in chondrocytes. Moreover, circPRKCH promoted HGF expression and activated HGF/c-MET by directly binding to miR-145. miR-145 knockdown or HGF overexpression significantly reversed circPRKCH knockdown-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes. Besides, miR-145 overexpression alleviated IL-1β-induced chondrocyte apoptosis and ECM degradation by inhibiting HGF/c-MET. Finally, circPRKCH knockdown reduced ECM degradation by regulating the miR-145/HGF axis in an experimental OA model in mice. CONCLUSION Our study demonstrated that circPRKCH promoted chondrocyte apoptosis and ECM degradation via the miR-145/HGF axis in OA, which may provide a novel target for OA treatment.
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Affiliation(s)
- Wenzhong Que
- Department of Rheumatology, Fuzhou No. 1 Hospital Affiliated with Fujian Medical University, Taijiang District, Fuzhou, 350000, Fujian Province, China.
| | - Huili Liu
- Department of Medical Technology, Zhangzhou Health Vocational College, Zhangzhou, 363000, Fujian Province, China
| | - Qinqin Yang
- College of Pharmacy, Fujian Medical University, Fuzhou, 350005, Fujian Province, China
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Zhou Y, Li H, Wang L. Mechanism of miR-34a in the metabolism of extracellular matrix in fibroblasts of stress urinary incontinence via Nampt-mediated autophagy. Cell Stress Chaperones 2022; 27:369-381. [PMID: 35666377 PMCID: PMC9346036 DOI: 10.1007/s12192-022-01278-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/12/2022] [Accepted: 05/15/2022] [Indexed: 01/03/2023] Open
Abstract
Stress urinary incontinence (SUI) is a troublesome hygienic problem that afflicts the female population and is associated with extracellular matrix (ECM). Herein, we investigated the effects of microRNA (miR)-34a on ECM metabolism in fibroblasts of SUI via mediating nicotinamide phosphoribosyl transferase (Nampt/NAmPRTase) and hope to find novel insights in the treatment of SUI. Firstly, the anterior vaginal wall tissues of SUI patients and the female vaginal wall fibroblasts (FVWFs) of non-SUI subjects were collected and identified. Then, FVWFs were treated with 10 ng/mL of interleukin 1 beta (IL-1β) to establish SUI cell models. Subsequently, miR-34a and Nampt expressions in both types of cells were detected via RT-qPCR. It was found that miR-34a was poorly expressed, while Nampt was highly expressed in SUI. Subsequently, IL-1β-treated FVWFs were transfected with miR-34a-mimic and pcDNA3.1-Nampt, respectively. Thereafter, RT-qPCR and Western blot detected that miR-34a overexpression increased COL1A, ACAN, and TIMP-1; decreased MMP-2 and MMP-9; and elevated LC3 II/I ratio, Beclin-1 expression, and the autophagosome number in IL-1β-treated FVWFs, while Nampt upregulation reversed the above outcomes. Then, dual-luciferase reporter gene assay detected that Nampt is a downstream target of miR-34a. Together, miR-34a overexpression promoted autophagy, inhibited ECM degradation in IL-1β-treated FVWFs, and ameliorated SUI via suppressing Nampt.
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Affiliation(s)
- Ying Zhou
- Department of Gynecology, Zhengzhou Central Hospital of Zhengzhou University, No. 195 Middle Tongbai Road, Zhengzhou, 450000, Henan Province, China
| | - Hongjuan Li
- Department of Gynecology, Zhengzhou Central Hospital of Zhengzhou University, No. 195 Middle Tongbai Road, Zhengzhou, 450000, Henan Province, China.
| | - Lu Wang
- Department of Gynecology, Zhengzhou Central Hospital of Zhengzhou University, No. 195 Middle Tongbai Road, Zhengzhou, 450000, Henan Province, China.
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22
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Lai X, Song Y, Tian J. CircCDK14 ameliorates interleukin-1β-induced chondrocyte damage by the miR-1183/KLF5 pathway in osteoarthritis. Autoimmunity 2022; 55:408-417. [PMID: 35723551 DOI: 10.1080/08916934.2022.2081843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND The pathogenesis of osteoarthritis (OA), an endemic and debilitating disease, remains unclear. The study aimed to reveal the role of circular RNA cyclin dependent kinase 14 (circCDK14) in OA development and the underlying mechanism. METHODS Human chondrocytes were stimulated by 10 ng/mL interleukin-1β (IL-1β) to mimic OA cell model. The RNA expression of circCDK14, microRNA-1183 (miR-1183) and kruppel like factor 5 (KLF5) was checked through quantitative real-time polymerase chain reaction. Western blot was employed to detect protein expression. Cell viability, proliferation and apoptosis were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine and flow cytometry analysis, respectively. Starbase online database was performed to identify the interaction between miR-1183 and circCDK14 or KLF5. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. RESULTS CircCDK14 and KLF5 expression were significantly decreased, while miR-1183 was increased in OA cartilage tissues and IL-1β-treated chondrocytes in comparison with controls. CircCDK14 overexpression attenuated the inhibitory effect of IL-1β treatment on cell proliferation and the promoting effects on cell apoptosis and extracellular matrix degradation. Additionally, miR-1183 was targeted by circCDK14, and miR-1183 mimics reversed circCDK14-mediated actions in IL-1β-treated chondrocytes. The knockdown of KLF5, a target mRNA of miR-1183, also rescued the effects of miR-1183 inhibitors in IL-1β-induced chondrocytes. Moreover, circCDK14 could induce KLF5 expression by interacting with miR-1183. Further, exosomal circCDK14 had a high diagnostic value in OA. CONCLUSION CircCDK14 reintroduction assuaged IL-1β-caused chondrocyte damage by the miR-1183/KLF5 pathway, providing a diagnostic biomarker for OA.
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Affiliation(s)
- Xiaowei Lai
- Department of Rheumatology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, China
| | - Yali Song
- Department of Rheumatology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, China
| | - Jimei Tian
- Department of Rheumatology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi City, China
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Fujii Y, Liu L, Yagasaki L, Inotsume M, Chiba T, Asahara H. Cartilage Homeostasis and Osteoarthritis. Int J Mol Sci 2022; 23:6316. [PMID: 35682994 PMCID: PMC9181530 DOI: 10.3390/ijms23116316] [Citation(s) in RCA: 94] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 05/29/2022] [Accepted: 06/03/2022] [Indexed: 01/27/2023] Open
Abstract
Healthy limb joints are important for maintaining health and attaining longevity. Endochondral ossification (the replacement of cartilage with bone, occurring during skeletal development) is essential for bone formation, especially in long-axis bones. In contrast to endochondral ossification, chondrocyte populations in articular cartilage persist and maintain joint tissue into adulthood. Articular cartilage, a connective tissue consisting of chondrocytes and their surrounding extracellular matrices, plays an essential role in the mechanical cushioning of joints in postnatal locomotion. Osteoarthritis (OA) pathology relates to disruptions in the balance between anabolic and catabolic signals, that is, the loss of chondrocyte homeostasis due to aging or overuse of cartilages. The onset of OA increases with age, shortening a person's healthy life expectancy. Although many people with OA experience pain, the mainstay of treatment is symptomatic therapy, and no fundamental treatment has yet been established. To establish regenerative or preventative therapies for cartilage diseases, further understanding of the mechanisms of cartilage development, morphosis, and homeostasis is required. In this review, we describe the general development of cartilage and OA pathology, followed by a discussion on anabolic and catabolic signals in cartilage homeostasis, mainly microRNAs.
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Affiliation(s)
- Yuta Fujii
- Department of Systems Biomedicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8501, Japan; (Y.F.); (L.L.); (L.Y.); (M.I.); (T.C.)
| | - Lin Liu
- Department of Systems Biomedicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8501, Japan; (Y.F.); (L.L.); (L.Y.); (M.I.); (T.C.)
| | - Lisa Yagasaki
- Department of Systems Biomedicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8501, Japan; (Y.F.); (L.L.); (L.Y.); (M.I.); (T.C.)
- Department of Periodontology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-851, Japan
| | - Maiko Inotsume
- Department of Systems Biomedicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8501, Japan; (Y.F.); (L.L.); (L.Y.); (M.I.); (T.C.)
| | - Tomoki Chiba
- Department of Systems Biomedicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8501, Japan; (Y.F.); (L.L.); (L.Y.); (M.I.); (T.C.)
| | - Hiroshi Asahara
- Department of Systems Biomedicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8501, Japan; (Y.F.); (L.L.); (L.Y.); (M.I.); (T.C.)
- Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
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24
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He M, Jia Z, Wen Y, Chen X. Circ_0043947 contributes to interleukin 1β-induced injury in chondrocytes by sponging miR-671-5p to up-regulate RTN3 expression in osteoarthritis pathology. J Orthop Surg Res 2022; 17:177. [PMID: 35331286 PMCID: PMC8944141 DOI: 10.1186/s13018-022-02970-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 01/25/2022] [Indexed: 12/21/2022] Open
Abstract
Objective Osteoarthritis (OA) is a chronic joint disease featured by articular cartilage degeneration and damage. Accumulating evidence have demonstrated the pivotal regulatory roles of circular RNAs in OA pathology. However, the role of circ_0043947 in OA progression and its associated mechanism remain largely unknown. Methods The expression of RNA and protein was determined by reverse transcription-quantitative polymerase chain reaction and Western blot assay. Cell viability was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was analyzed by 5-Ethynyl-2′-deoxyuridine (EdU) assay and flow cytometry. Cell apoptosis was assessed by flow cytometry. Enzyme linked immunosorbent assay was conducted to analyze the release of pro-inflammatory cytokines. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to confirm the target interaction between microRNA-671-5p (miR-671-5p) and circ_0043947 or reticulon 3 (RTN3). Results Interleukin 1β (IL-1β) stimulation up-regulated the expression of circ_0043947 in chondrocytes. IL-1β treatment restrained the viability and proliferation and induced the apoptosis, extracellular matrix degradation and inflammatory response of chondrocytes partly by up-regulating circ_0043947. Circ_0043947 interacted with miR-671-5p, and miR-671-5p silencing largely reversed circ_0043947 knockdown-mediated protective effects in IL-1β-induced chondrocytes. miR-671-5p interacted with the 3′ untranslated region (3′UTR) of RTN3. miR-671-5p overexpression attenuated IL-1β-induced injury in chondrocytes, and these protective effects were largely overturned by the overexpression of RTN3. Circ_0043947 acted as a molecular sponge for miR-671-5p to up-regulate RTN3 level in chondrocytes. Conclusion Circ_0043947 silencing alleviated IL-1β-induced injury in chondrocytes by targeting miR-671-5p/RTN3 axis.
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Affiliation(s)
- Min He
- Department of Joint Surgery, Pingxiang People's Hospital, Pingxiang City, 337055, Jiangxi, China
| | - Zhihe Jia
- Department of Joint Surgery, Pingxiang People's Hospital, Pingxiang City, 337055, Jiangxi, China
| | - Yiying Wen
- Department of Joint Surgery, Pingxiang People's Hospital, Pingxiang City, 337055, Jiangxi, China
| | - Xiaolin Chen
- Department of Laboratory, Pingxiang People's Hospital, No. 8 Wugong Shanzhong Avenue, Development Zone, Pingxiang City, Jiangxi, China.
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25
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Luo S, Li W, Wu W, Shi Q. Next-Generation Sequencing of Circular RNAs Reveals the Molecular Mechanisms of Chondrogenic Differentiation in Human Adipose-derived Stem Cells. Cell Biochem Biophys 2022; 80:443-455. [PMID: 35257277 DOI: 10.1007/s12013-022-01062-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 01/19/2022] [Indexed: 11/24/2022]
Abstract
Adipose-derived stem cells are one of the potential sources of cells for the treatment of cartilage defects. This study aimed to investigate the molecular mechanisms that account for the chondrogenic differentiation of human adipose-derived stem cells (hADSCs). We employed integrin β1 (ITGB1) overexpression to induce chondrogenic differentiation of hADSCs. Next-generation sequencing was used to determine the mRNAs and circular RNAs (circRNAs) expression profiles in ITGB1-overexpresing and negative control cells. The potential functions of differentially expressed mRNAs were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Moreover, differentially expressed circRNAs with the greatest fold change were validated by polymerase chain reaction (PCR), Sanger sequencing, and quantitative real-time PCR (qRT-PCR). These three circRNAs and their downstream microRNAs and mRNAs were used to construct a circRNA-microRNA-mRNA interaction network. The results showed that we identified 713 differentially expressed circRNAs (150 upregulated and 563 downregulated in ITGB1-overexpressing hADSCs versus negative control cells, respectively). Meanwhile, 2383 mRNAs were differentially expressed between two groups (1672 upregulated and 711 downregulated in ITGB1-overexpressing cells compared with the negative control cells). The GO and KEGG analysis results showed that the differentially expressed mRNAs were enriched in biological processes, cellular components, and molecular functions, especially in the phosphatidylinositol 3-kinase (PI3K)-AKT and mitogen-activated protein kinase signaling pathways. Three differentially expressed circRNAs, including hsa_circ_0071127, hsa_circ_0008637, and hsa_circ_0020028, were validated by qRT-PCR. Moreover, the circRNA-microRNA-mRNA network predicted that fibroblast growth factor 2 (FGF2) was a common node regulated by these three circRNAs through several microRNAs, including miR-195-3p, miR-205-3p, and miR-152-3p. We further found that the knockdown of hsa_circ_0020028, but not the two other circRNAs, significantly reduced FGF2 mRNA expression in hADSCs. Furthermore, the knockdown of hsa_circ_0020028 significantly inhibited the protein expression of FGF2, chondrogenic differentiation markers (COL II, aggrecan, and SOX9), and PI3K/AKT signaling in ITGB1-overexpressing hADSCs. This study uncovered the differentially expressed mRNA and circRNA profiles in the chondrogenic differentiation of hADSCs induced by ITGB1 overexpression. Our findings demonstrate that hsa_circ_0020028 regulates the ITGB1 overexpression-mediated chondrogenic differentiation of hADSCs through regulation of FGF2-related signaling pathways.
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Affiliation(s)
- Simin Luo
- Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.,Chaoshan Hospital, The First Affiliated Hospital of Jinan University, Chaozhou, 515700, China
| | - Wuji Li
- Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China
| | - Wenrui Wu
- Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China
| | - Qiping Shi
- Department of Endocrine, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
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Zhang Z, Zhao T, Xu H, Wu X. Circ_0008365 Suppresses Apoptosis, Inflammation and Extracellular Matrix Degradation of IL-1β-treated Chondrocytes in Osteoarthritis by Regulating miR-324-5p/BMPR2/NF-κB Signaling Axis. Immunol Invest 2022; 51:1598-1611. [PMID: 35172669 DOI: 10.1080/08820139.2021.2001496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Recent studies have revealed that circular RNAs (circRNAs) play crucial roles in the progression of osteoarthritis (OA). This study aimed to investigate the biological function and regulatory mechanism of circ_0008365 in OA. METHODS OA cell model in vitro was established in chondrocytes by treatment with Interleukin-1β (IL-1β). The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of circ_0008365, microRNA-324-5p (miR-324-5p) and bone morphogenetic protein type 2 receptor (BMPR2) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was assessed using flow cytometry and caspase3 activity assays. The protein expression was determined via a western blot assay. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down assays were used to analyze the correlation between targets. RESULTS IL-1β level and miR-324-5p expression were increased, while circ_0008365 was downregulated in OA patients. IL-1β treatment-induced cell apoptosis, inflammation and extracellular matrix (ECM) degradation in chondrocytes. Besides, circ_0008365 overexpression partly relieved IL-1β-induced cell damage in chondrocytes. Circ_0008365 could interact with miR-324-5p, and BMPR2 was a downstream target of miR-324-5p. Overexpression of miR-324-5p or BMPR2 knockdown partly overturned the inhibiting effect of circ_0008365 on cell damage in IL-1β-induced chondrocytes. In addition, circ_0008365 inactivated NF-κB pathway via regulating miR-324-5p/BMPR2 axis. CONCLUSION Circ_0008365 reduced IL-1β-induced cell damage in chondrocytes via inactivating NF-κB signaling pathway and regulating miR-324-5p/BMPR2 axis.Abbreviations OA: osteoarthritis; BMPR2: bone morphogenetic protein type 2 receptor.
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Affiliation(s)
- Zilong Zhang
- Department of Spine, Zaozhuang Municipal Hospital, Zaozhuang City, China
| | - Teng Zhao
- Department of Orthopedics, Zaozhuang Hospital, Zaozhuang Mining Group, Jining City, China
| | - Haiwei Xu
- Department of Orthopedics, Zaozhuang Hospital, Zaozhuang Mining Group, Jining City, China
| | - Xing Wu
- Department of Orthopedics, Tennan Hospital, Zaozhuang Mining Group, Jining City, China
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27
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Luobu Z, Wang L, Jiang D, Liao T, Luobu C, Qunpei L. CircSCAPER contributes to IL-1β-induced osteoarthritis in vitro via miR-140-3p/EZH2 axis. Bone Joint Res 2022; 11:61-72. [PMID: 35103493 PMCID: PMC8882325 DOI: 10.1302/2046-3758.112.bjr-2020-0482.r2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Aims Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study. Methods In vitro cultured human normal chondrocyte C28/I2 was exposed to interleukin (IL)-1β to mimic the microenvironment of OA. The expression of circSCAPER, microRNA (miR)-140-3p, and enhancer of zeste homolog 2 (EZH2) was detected using quantitative real-time polymerase chain reaction and Western blot assays. The extracellular matrix (ECM) degradation, proliferation, and apoptosis of chondrocytes were determined using Western blot, cell counting kit-8, and flow cytometry assays. Targeted relationships were predicted by bioinformatic analysis and verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein were detected using Western blot assays. Results CircSCAPER was highly expressed in OA cartilage tissues and IL-1β-induced chondrocytes. Knockdown of circSCAPER reduced IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes. Mechanistically, circSCAPER directly bound to miR-140-3p, and miR-140-3p inhibition reversed the effects of circSCAPER knockdown on IL-1β-induced chondrocytes. miR-140-3p was verified to target EZH2, and overexpression of miR-140-3p protected chondrocytes against IL-1β-induced dysfunction via targeting EZH2. Additionally, we confirmed that circSCAPER could regulate EZH2 through sponging miR-140-3p, and the circSCAPER/miR-140-3p/EZH2 axis could activate the PI3K/AKT pathway. Conclusion CircSCAPER promoted IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes via regulating miR-140-3p/EZH2 axis, which gained a new insight into the pathogenesis of OA. Cite this article: Bone Joint Res 2022;11(2):61–72.
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Affiliation(s)
- Zhaxi Luobu
- Department of Orthopedics, Lhasa People's Hospital, Lhasa City, Tibet, China
| | - Lei Wang
- Department of Orthopedics, Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Dahai Jiang
- Department of Orthopedics, Lhasa People's Hospital, Lhasa City, Tibet, China
| | - Tao Liao
- Department of Orthopedics, Lhasa People's Hospital, Lhasa City, Tibet, China
| | - Ciren Luobu
- Department of Orthopedics, Lhasa People's Hospital, Lhasa City, Tibet, China
| | - Luosong Qunpei
- Department of Orthopedics, Lhasa People's Hospital, Lhasa City, Tibet, China
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28
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Interplay between circular RNA, microRNA, and human diseases. Mol Genet Genomics 2022; 297:277-286. [PMID: 35084582 DOI: 10.1007/s00438-022-01856-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 01/04/2022] [Indexed: 12/09/2022]
Abstract
Circular RNAs (circRNAs) are endogenous RNA formed by the back splicing process. They are ubiquitous, stable, evolutionally conserved, and are tissue-specific. The biochemical and molecular features of circRNAs hold the potential to be used as biomarkers in various diseases to achieve pharmacological goals. CircRNAs have numerous latent modes of action, from acting as sponges for microRNAs and RNA binding proteins to serve as transcriptional regulators, epigenetic alterations, etc. Dysregulated functioning of several circular RNAs lead to the progression of a plethora of diseases. Due to their extremely stable nature and amazing tissue specificity, circRNAs have paved the way for advanced clinical studies as a novel method of early disease detection and treatment efficacy. Therefore, they have been recognized as a latent diagnostic biomarker for neurodegenerative diseases, diabetes, osteoarthritis, and cardiovascular diseases.
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29
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Zhu J, Guo Y. Circ_0020093 Overexpression Alleviates Interleukin-1 Beta-induced Inflammation, Apoptosis and Extracellular Matrix Degradation in Human Chondrocytes by Targeting the miR-181a-5p/ERG Pathway. Immunol Invest 2022; 51:1660-1677. [PMID: 35012421 DOI: 10.1080/08820139.2021.2021938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Osteoarthritis (OA) is a well-known chronic degenerative joint disease, with multiple changes in the phenotype of chondrocytes. Circular RNAs (circRNAs) have been shown to be involved in various human diseases, including OA. The purpose of this study was to determine the role of circ_0020093 in OA pathological changes in vitro. C28/I2 cells were treated with interleukin-1 beta (IL-1β) to mimic OA pathological conditions. The expression levels of circ_0020093, miR-181a-5p and ETS-related gene (ERG) mRNA were measured by quantitative real-time PCR (qRT-PCR). For functional analyses, cell proliferative capacity was detected using EdU assay and CCK-8 assay. Inflammatory response was assessed by determining the release of pro-inflammatory factors using ELISA kits. Cell apoptosis was examined by flow cytometry assay. The levels of apoptosis-related proteins and extracellular matrix (ECM)-associated proteins were assessed by Western blot. The binding relationship between miR-181a-5p and circ_0020093 or ERG was confirmed by RNA pull-down assay, dual-luciferase reporter assay or RIP assay. The expression level of circ_0020093 was decreased in IL-1β-treated C28/I2 cells. Circ_0020093 overexpression relieved inflammatory responses, cell apoptosis and ECM degradation in IL-1β-induced C28/I2 cells. Circ_0020093 directly targeted miR-181a-5p, and miR-181a-5p bound to the 3' -untranslated region (3'UTR) of ERG to regulate ERG expression. Circ_0020093 overexpression promoted the expression of ERG by sponging miR-181a-5p. Rescue experiments showed that miR-181a-5p overexpression or ERG knockdown could reverse the inhibitory effects of circ_0020093 overexpression on the pathological changes in IL-1β-induced C28/I2 cells. Circ_0020093 overexpression alleviated IL-1β-induced human chondrocyte inflammatory injury, apoptosis and ECM degradation by targeting miR-181a-5p/ERG pathway.
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Affiliation(s)
- Jun Zhu
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang City, Hubei Province, China
| | - Yongchun Guo
- Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang City, Hubei Province, China
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30
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Kim J. Dysregulated circular RNAs and their pathological implications in knee osteoarthritis: potential novel therapeutic targets and diagnostic biomarkers. ALL LIFE 2022. [DOI: 10.1080/26895293.2021.2020172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Jaehee Kim
- Department of Alternative Medicine, Graduate School of Alternative Medicine, Kyonggi University (Seoul Campus), Seoul, Republic of Korea
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31
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Kong H, Sun ML, Zhang XA, Wang XQ. Crosstalk Among circRNA/lncRNA, miRNA, and mRNA in Osteoarthritis. Front Cell Dev Biol 2022; 9:774370. [PMID: 34977024 PMCID: PMC8714905 DOI: 10.3389/fcell.2021.774370] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Osteoarthritis (OA) is a joint disease that is pervasive in life, and the incidence and mortality of OA are increasing, causing many adverse effects on people's life. Therefore, it is very vital to identify new biomarkers and therapeutic targets in the clinical diagnosis and treatment of OA. ncRNA is a nonprotein-coding RNA that does not translate into proteins but participates in protein translation. At the RNA level, it can perform biological functions. Many studies have found that miRNA, lncRNA, and circRNA are closely related to the course of OA and play important regulatory roles in transcription, post-transcription, and post-translation, which can be used as biological targets for the prevention, diagnosis, and treatment of OA. In this review, we summarized and described the various roles of different types of miRNA, lncRNA, and circRNA in OA, the roles of different lncRNA/circRNA-miRNA-mRNA axis in OA, and the possible prospects of these ncRNAs in clinical application.
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Affiliation(s)
- Hui Kong
- College of Kinesiology, Shenyang Sport University, Shenyang, China
| | - Ming-Li Sun
- College of Kinesiology, Shenyang Sport University, Shenyang, China
| | - Xin-An Zhang
- College of Kinesiology, Shenyang Sport University, Shenyang, China
| | - Xue-Qiang Wang
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China.,Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, China
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Dong Q, Han Z, Tian L. Identification of Serum Exosome-Derived circRNA-miRNA-TF-mRNA Regulatory Network in Postmenopausal Osteoporosis Using Bioinformatics Analysis and Validation in Peripheral Blood-Derived Mononuclear Cells. Front Endocrinol (Lausanne) 2022; 13:899503. [PMID: 35757392 PMCID: PMC9218277 DOI: 10.3389/fendo.2022.899503] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 05/05/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Osteoporosis is one of the most common systemic metabolic bone diseases, especially in postmenopausal women. Circular RNA (circRNA) has been implicated in various human diseases. However, the potential role of circRNAs in postmenopausal osteoporosis (PMOP) remains largely unknown. The study aims to identify potential biomarkers and further understand the mechanism of PMOP by constructing a circRNA-associated ceRNA network. METHODS The PMOP-related datasets GSE161361, GSE64433, and GSE56116 were downloaded from the Gene Expression Omnibus (GEO) database and were used to obtain differentially expressed genes (DEGs). Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to determine possible relevant functions of differentially expressed messenger RNAs (mRNAs). The TRRUST database was used to predict differential transcription factor (TF)-mRNA regulatory pairs. Afterwards, combined CircBank and miRTarBase, circRNA-miRNA as well as miRNA-TF pairs were constructed. Then, a circRNA-miRNA-TF-mRNA network was established. Next, the correlation of mRNAs, TFs, and PMOP was verified by the Comparative Toxicogenomics Database. And expression levels of key genes, including circRNAs, miRNAs, TFs, and mRNAs in the ceRNA network were further validated by quantitative real-time PCR (qRT-PCR). Furthermore, to screen out signaling pathways related to key mRNAs of the ceRNA network, Gene Set Enrichment Analysis (GSEA) was performed. RESULTS A total of 1201 DE mRNAs, 44 DE miRNAs, and 1613 DE circRNAs associated with PMOP were obtained. GO function annotation showed DE mRNAs were mainly related to inflammatory responses. KEGG analysis revealed DE mRNAs were mainly enriched in osteoclast differentiation, rheumatoid arthritis, hematopoietic cell lineage, and cytokine-cytokine receptor interaction pathways. We first identified 26 TFs and their target mRNAs. Combining DE miRNAs, miRNA-TF/mRNA pairs were obtained. Combining DE circRNAs, we constructed the ceRNA network contained 6 circRNAs, 4 miRNAs, 4 TFs, and 12 mRNAs. The expression levels of most genes detected by qRT-PCR were generally consistent with the microarray results. Combined with the qRT-PCR validation results, we eventually identified the ceRNA network that contained 4 circRNAs, 3 miRNAs, 3 TFs, and 9 mRNAs. The GSEA revealed that 9 mRNAs participate in many important signaling pathways, such as "olfactory transduction", "T cell receptor signaling pathway", and "neuroactive ligand-receptor interaction". These pathways have been reported to the occurrence and development of PMOP. To sum up, key mRNAs in the ceRNA network may participate in the development of osteoporosis by regulating related signal pathways. CONCLUSIONS A circRNA-associated ceRNA network containing TFs was established for PMOP. The study may help further explore the molecular mechanisms and may serve as potential biomarkers or therapeutic targets for PMOP.
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Affiliation(s)
- Qianqian Dong
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China
- Clinical Research Center for Metabolic Disease, Gansu Provincial Hospital, Lanzhou, China
| | - Ziqi Han
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China
- Clinical Research Center for Metabolic Disease, Gansu Provincial Hospital, Lanzhou, China
| | - Limin Tian
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China
- Clinical Research Center for Metabolic Disease, Gansu Provincial Hospital, Lanzhou, China
- *Correspondence: Limin Tian,
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Zhang H, Wang L, Xiang Y, Wang Y, Li H. Nampt promotes fibroblast extracellular matrix degradation in stress urinary incontinence by inhibiting autophagy. Bioengineered 2021; 13:481-495. [PMID: 34967693 PMCID: PMC8805819 DOI: 10.1080/21655979.2021.2009417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Stress urinary incontinence (SUI) is defined as involuntary urinary leakage happening in exertion. Nicotinamide phosphoribosyltransferase (Nampt) is seldom researched in the pathogenesis of SUI. Accordingly, the current study set out to elucidate the role of Nampt in SUI progression. Firstly, we determined Nampt expression patterns in SUI patients and rat models. In addition, fibroblasts were obtained from the anterior vaginal wall tissues of non-SUI patients and subjected to treatment with different concentrations of interleukin-1β (IL-1β), followed by quantification of Nampt expressions in fibroblasts. Subsequently, an appropriate concentration of IL-1β was selected to treat anterior vaginal wall fibroblasts. Nampt was further silenced in IL-1β-treated fibroblasts to assess the role of Nampt in autophagy and extracellular matrix (ECM) degradation. Lastly, functional rescue assays were carried out to inhibit autophagy and evaluate the role of autophagy in the mechanism of Nampt modulating IL-1β-treated fibroblast ECM degradation. It was found that Nampt was highly-expressed in SUI patients and rat models and IL-1β-treated fibroblasts. On the other hand, Nampt silencing was found to suppress ECM degradation and promote SUI fibroblast autophagy. Additionally, inhibition of autophagy attenuated the inhibitory effects of Nampt silencing on SUI fibroblast ECM degradation. Collectively, our findings revealed that Nampt was over-expressed in SUI, whereas Nampt silencing enhanced SUI fibroblast autophagy, and thereby inhibited ECM degradation.
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Affiliation(s)
- Hui Zhang
- Gynecology II Ward, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China
| | - Lu Wang
- Gynecology II Ward, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yuancui Xiang
- Gynecology II Ward, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China
| | - Yali Wang
- Gynecology II Ward, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China
| | - Hongjuan Li
- Gynecology II Ward, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China
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Deng J, Zong Z, Su Z, Chen H, Huang J, Niu Y, Zhong H, Wei B. Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect. Front Pharmacol 2021; 12:772678. [PMID: 34887766 PMCID: PMC8649959 DOI: 10.3389/fphar.2021.772678] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/04/2021] [Indexed: 12/27/2022] Open
Abstract
Osteoarthritis (OA) is a degenerative joint disease in the musculoskeletal system with a relatively high incidence and disability rate in the elderly. It is characterized by the degradation of articular cartilage, inflammation of the synovial membrane, and abnormal structure in the periarticular and subchondral bones. Although progress has been made in uncovering the molecular mechanism, the etiology of OA is still complicated and unclear. Nevertheless, there is no treatment method that can effectively prevent or reverse the deterioration of cartilage and bone structure. In recent years, in the field of pharmacology, research focus has shifted to disease prevention and early treatment rather than disease modification in OA. Biologic agents become more and more attractive as their direct or indirect intervention effects on the initiation or development of OA. In this review, we will discuss a wide spectrum of biologic agents ranging from DNA, noncoding RNA, exosome, platelet-rich plasma (PRP), to protein. We searched for key words such as OA, DNA, gene, RNA, exosome, PRP, protein, and so on. From the pharmacological aspect, stem cell therapy is a very special technique, which is not included in this review. The literatures ranging from January 2016 to August 2021 were included and summarized. In this review, we aim to help readers have a complete and precise understanding of the current pharmacological research progress in the intervention of OA from the biological aspect and provide an indication for the future translational studies.
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Affiliation(s)
- Jinxia Deng
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Zhixian Zong
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Zhanpeng Su
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Haicong Chen
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Jianping Huang
- College of Dentistry, Yonsei University, Seoul, South Korea.,Department of Stomatology, Guangdong Medical University, Zhanjiang, China
| | - Yanru Niu
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Huan Zhong
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
| | - Bo Wei
- Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China
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Apizi X, Talifujiang D, Kasimu A, Zhang X, Yiming A, Ma X, Song Q, Wang D. Circular RNA mmu_circ_0001598 Contributes to IL-1 β-Induced Osteoarthritis Progression by Regulating miR-127-3p. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:2793379. [PMID: 34917303 PMCID: PMC8670906 DOI: 10.1155/2021/2793379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/07/2021] [Accepted: 11/13/2021] [Indexed: 12/05/2022]
Abstract
Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. In this study, we found that circ_0001598 was significantly upregulated in chondrocytes treated with IL-1β and in cartilage tissue from mice with severed anterior cruciate ligament surgery (ACLT) induced OA models. Interference with circ_0001598 in vitro restored IL-1β-induced chondrocyte proliferation and apoptosis. Silencing circ_0001598 significantly alleviated ACLT-induced OA in mice. Mechanistically, knockdown of circ_0001598 affected chondrocyte proliferation, apoptosis, and matrix degradation by regulating miR-127-3p. Taken together, our results demonstrate the fundamental role of circ_0001598 and provide new ideas for the prevention and treatment of osteoarthritis.
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Affiliation(s)
- Xierenguli Apizi
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Dilibaier Talifujiang
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Aziguli Kasimu
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Xue Zhang
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Aibibula Yiming
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Xin Ma
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Qingshan Song
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
| | - Dequan Wang
- Department of Pain Treatment, People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous Region, Urumqi 830001, China
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Ghafouri-Fard S, Poulet C, Malaise M, Abak A, Mahmud Hussen B, Taheriazam A, Taheri M, Hallajnejad M. The Emerging Role of Non-Coding RNAs in Osteoarthritis. Front Immunol 2021; 12:773171. [PMID: 34912342 PMCID: PMC8666442 DOI: 10.3389/fimmu.2021.773171] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 11/10/2021] [Indexed: 12/16/2022] Open
Abstract
Osteoarthritis (OS) is the most frequent degenerative condition in the joints, disabling many adults. Several abnormalities in the articular cartilage, subchondral bone, synovial tissue, and meniscus have been detected in the course of OA. Destruction of articular cartilage, the formation of osteophytes, subchondral sclerosis, and hyperplasia of synovial tissue are hallmarks of OA. More recently, several investigations have underscored the regulatory roles of non-coding RNAs (ncRNAs) in OA development. Different classes of non-coding RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been reported to affect the development of OA. The expression level of these transcripts has also been used as diagnostic tools in OA. In the present article, we aimed at reporting the role of these transcripts in this process. We need to give a specific angle on the pathology to provide meaningful thoughts on it.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Christophe Poulet
- Department of Rheumatology, University Hospital of Liège (CHULiege), Liège, Belgium
- Fibropôle Research Group, University Hospital of Liège (CHULiege), Liège, Belgium
- GIGA-I3 Research Group, GIGA Institute, University of Liège (ULiege) and University Hospital of Liège (CHULiege), Liège, Belgium
| | - Michel Malaise
- Department of Rheumatology, University Hospital of Liège (CHULiege), Liège, Belgium
- Fibropôle Research Group, University Hospital of Liège (CHULiege), Liège, Belgium
- GIGA-I3 Research Group, GIGA Institute, University of Liège (ULiege) and University Hospital of Liège (CHULiege), Liège, Belgium
| | - Atefe Abak
- Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
- Center of Research and Strategic Studies, Lebanese French University, Erbil, Iraq
| | - Afshin Taheriazam
- Department of Orthopedics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany
- *Correspondence: Mohammad Taheri, ; Mohammad Hallajnejad,
| | - Mohammad Hallajnejad
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- *Correspondence: Mohammad Taheri, ; Mohammad Hallajnejad,
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Zheng YL, Song G, Guo JB, Su X, Chen YM, Yang Z, Chen PJ, Wang XQ. Interactions Among lncRNA/circRNA, miRNA, and mRNA in Musculoskeletal Degenerative Diseases. Front Cell Dev Biol 2021; 9:753931. [PMID: 34708047 PMCID: PMC8542847 DOI: 10.3389/fcell.2021.753931] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/22/2021] [Indexed: 12/18/2022] Open
Abstract
Musculoskeletal degenerative diseases (MSDDs) are pathological conditions that affect muscle, bone, cartilage, joint and connective tissue, leading to physical and functional impairments in patients, mainly consist of osteoarthritis (OA), intervertebral disc degeneration (IDD), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression that play an important role in biological regulation, involving in chondrocyte proliferation and apoptosis, extracellular matrix degradation and peripheral blood mononuclear cell inflammation. Research on MSDD pathogenesis, especially on RA and AS, is still in its infancy and major knowledge gaps remain to be filled. The effects of lncRNA/circRNA-miRNA-mRNA axis on MSDD progression help us to fully understand their contribution to the dynamic cellular processes, provide the potential OA, IDD, RA and AS therapeutic strategies. Further studies are needed to explore the mutual regulatory mechanisms between lncRNA/circRNA regulation and effective therapeutic interventions in the pathology of MSDD.
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Affiliation(s)
- Yi-Li Zheng
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
| | - Ge Song
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
| | - Jia-Bao Guo
- The Second School of Clinical Medicine, Xuzhou Medical University, Xuzhou, China
| | - Xuan Su
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
| | - Yu-Meng Chen
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
| | - Zheng Yang
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
| | - Pei-Jie Chen
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China
| | - Xue-Qiang Wang
- Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, China.,Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, China
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Wang J, Yang B, Wu C, Guo Y, Jiang X, Zhang Y. Role of circular RNAs in osteoarthritis (Review). Exp Ther Med 2021; 22:1279. [PMID: 34594416 PMCID: PMC8456490 DOI: 10.3892/etm.2021.10714] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 08/11/2021] [Indexed: 11/12/2022] Open
Abstract
Osteoarthritis (OA) is a chronic bone and joint disease characterized by articular cartilage degeneration and joint inflammation. OA is the most common form of arthritis, and the major clinical manifestations of OA are chronic pain and joint activity disorder, which severely affect patients' quality of life. Circular RNA (circRNA) is a type of non-coding RNA that is ubiquitous in eukaryotic cells. Unlike standard linear RNAs, they form a covalently closed continuous loop without 5' or 3' polarity. They are usually considered as byproducts of mis-splicing or mRNA processing. CircRNAs have been detected and identified in numerous species. Various studies have confirmed that certain circRNAs are differentially expressed in OA cartilage and are closely associated with a variety of pathological processes of OA, including extracellular matrix degradation, inflammation and apoptosis. The present study reviewed the latest research on circRNAs in the pathogenesis of OA, providing a novel direction for the prevention, diagnosis and treatment of OA.
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Affiliation(s)
- Jicheng Wang
- Department of Joint Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Bo Yang
- Department of Joint Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Changkun Wu
- Department of Joint Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Yongzhi Guo
- Department of Joint Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Xin Jiang
- Department of Joint Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Yangyang Zhang
- Department of Joint Surgery, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
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Feng M, Jing L, Cheng J, An S, Huang J, Yan Q. Circ_0020093 ameliorates IL-1β-induced apoptosis and extracellular matrix degradation of human chondrocytes by upregulating SPRY1 via targeting miR-23b. Mol Cell Biochem 2021; 476:3623-3633. [PMID: 34046827 PMCID: PMC8382646 DOI: 10.1007/s11010-021-04186-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 05/18/2021] [Indexed: 01/06/2023]
Abstract
Osteoarthritis (OA) is a chronic disease characterized by articular cartilage degeneration and uncontrolled chondrocyte apoptosis. At present, accumulating evidence introduces that circular RNA (circRNA) is involved in the development of OA. The aim of our study was to explore the role and the functional mechanism of circ_0020093 in OA cell model. Human chondrocytes were treated with interleukin-1 beta (IL-1β) to construct OA model. The expression of circ_0020093, miR-23b, and Sprouty 1 (SPRY1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis was assessed by flow cytometry assay. The expression of extracellular matrix (ECM)-associated markers and SPRY1 protein level was detected by qRT-PCR and Western blot. Bioinformatics analysis-predicted relationship between miR-23b and circ_0020093 or SPRY1 was further verified by dual-luciferase reporter assay and RNA pull-down assay. In this study, we found that the expression of circ_0020093 and SPRY1 was declined, while miR-23b expression was elevated in IL-1β-treated chondrocytes. IL-1β induced chondrocyte apoptosis and ECM degradation, while these negative effects were alleviated by circ_0020093 overexpression or miR-23b inhibition. MiR-23b was a target of circ_0020093, and SPRY1 was a downstream target of miR-23b. Rescue experiments showed that miR-23b enrichment reversed the role of circ_0020093 overexpression, and SPRY1 knockdown also reversed the effects of miR-23b inhibition. Importantly, circ_0020093 positively regulated SPRY1 expression by targeting miR-23b. In conclusion, circ_0020093 ameliorates IL-1β-induced apoptosis and ECM degradation of human chondrocytes by regulating the miR-23b/SPRY1 axis.
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Affiliation(s)
- Mingli Feng
- Department of Orthopaedics, Xuanwu Hospital, Capital Medical University, Changchun Ave 45, Xicheng District, Beijing, 100053, China.
| | - Lin Jing
- Department of Orthopaedics, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jingbo Cheng
- Department of Orthopaedics, Xuanwu Hospital, Capital Medical University, Changchun Ave 45, Xicheng District, Beijing, 100053, China
| | - Shuai An
- Department of Orthopaedics, Xuanwu Hospital, Capital Medical University, Changchun Ave 45, Xicheng District, Beijing, 100053, China
| | - Jiang Huang
- Department of Orthopaedics, Xuanwu Hospital, Capital Medical University, Changchun Ave 45, Xicheng District, Beijing, 100053, China
| | - Qi Yan
- Department of Orthopaedics, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Li H, Liu Z, Guo X, Zhang M. Circ_0128846/miR-140-3p/JAK2 Network in Osteoarthritis Development. Immunol Invest 2021; 51:1529-1547. [PMID: 34544313 DOI: 10.1080/08820139.2021.1981930] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Circular RNAs (circRNAs) titrate the function of microRNAs (miRNAs), regulate transcription, and interfere with splicing. This study attempted to confirm the role of a novel circRNA circ_0128846 during osteoarthritis (OA) progression. Tissues and chondrocytes were isolated from OA patients. Overexpression and knockdown of target genes were generated using cell transfection and siRNA interference. Expression levels of genes were measured by qRT-PCR, Western blot, and immunohistochemistry, respectively. The interactions among circ_0128846, miR-140-3p, and JAK2 were verified by bioinformatics prediction, a dual-luciferase reporter assay, and RNA immunoprecipitation assay. The role of circ_0128846 in vivo was confirmed by the construction of experimental OA rats. Pathological changes were evaluated by hematoxylin and eosin and Safranin O staining. In OA patients, the level of circ_0128846 and JAK2 were up-regulated with down-regulated level of miR-140-3p. Circ_0128846 was principally located in the cytoplasm. Circ_0128846 silence enhanced cells viability, but reduced apoptosis rate and inflammatory response, which was obviously reversed by miR-140-3p knockdown. The overexpression of JAK2 reversed the effects of miR-140-3p on cell phenotypes. Circ_0128846 silence suppressed the level of MMP-13 and promoted the expression of collagen II by up-regulating miR-140-3p and down-regulating JAK2 in OA cells. Results of animal experiments demonstrated that circ_0128846 silence promoted collagen II expression and attenuated the OA progression by regulating the miR-140-3p/JAK2 axis. Circ_0128846 contributes to OA development through acting as a sponge RNA for miR-140-3p and thereby increasing JAK2 expression. Results indicated that targeting circ_0128846 may have the potential to alleviate OA progression.Abbreviations:circRNAs: Circular RNAs; miRNAs: microRNAs; OA: osteoarthritis; RIP: RNA immunoprecipitation; H&E: hematoxylin and eosin; ncRNAs: noncoding RNAs; ceRNA: competitive endogenous RNA; DMEM: Dulbecco's modified Eagle's medium; PBS: phosphate buffered saline; OE-circ_0128846: overexpression vector for circ_0128846; pcDNA3.1-JAK2: pcDNA3.1 overexpression vector for Janus kinase 2; NC: negative control; CCK-8: Cell Counting Kit-8; PI: propidium iodide; WT: Wild-type; mutants (MUT); SD rats: Sprague Dawley rats; DMM: destabilization of medial meniscus; IHC: immunohistochemistry; DAB: diaminobenzene; pre-Mrna: precursor mRNA.
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Affiliation(s)
- Hongjun Li
- Department of Rheumatology and Immunology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Zhongyu Liu
- Department of Knee Joint, Tianjin Hospital, Tianjin, China
| | - Xiaoyun Guo
- Department of Rheumatology and Immunology, The Second Hospital of Tianjin Medical University, Tianjin, China.,Department of Nephrology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Mei Zhang
- Department of Rheumatology and Immunology, Tianjin Medical University Genenral Hospital, Tianjin, China
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Exosome-mediated circ_0001846 participates in IL-1β-induced chondrocyte cell damage by miR-149-5p-dependent regulation of WNT5B. Clin Immunol 2021; 232:108856. [PMID: 34536574 DOI: 10.1016/j.clim.2021.108856] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 09/07/2021] [Accepted: 09/13/2021] [Indexed: 12/22/2022]
Abstract
AIMS Osteoarthritis (OA) is the leading cause of physical disability in middle-aged and elderly people globally. Previous studies have revealed that circular RNA (circRNA) is involved in the pathogenesis of OA. In this study, we studied the role of circ_0001846 in interleukin-1β (IL-1β)-induced OA progression. METHODS Twenty-one patients with OA and 17 volunteers were recruited for the collection of articular cartilage tissues. The expression of circ_0001846, microRNA-149-5p (miR-149-5p) and Wingless-type MMTV integration site family, member 5B (WNT5B) was detected by quantitative real-time polymerase chain reaction. The protein expression was determined by western blot analysis. Cell viability, apoptosis, invasion and migration were demonstrated by cell counting kit-8, flow cytometry analysis, transwell invasion and wound-healing assays, respectively. The levels of IL-6 and tumor necrosis factor-α were detected by Enzyme-linked immunosorbent assay. The interaction between miR-149-5p and circ_0001846 or WNT5B was predicted by starbase online database, and proved by dual-luciferase reporter and RIP assays. RESULTS Circ_0001846 and WNT5B expression were upregulated, while miR-149-5p expression was downregulated in articular cartilage tissues from patients with OA and IL-1β-treated CHON-001 cells compared with normal articular cartilage tissues or untreated CHON-001 cells. Circ_0001846 expression was increased in IL-1β-treated CHON-001 cell exosomes. Circ_0001846 knockdown reversed IL-1β-mediated cell proliferation, apoptosis, migration, invasion, inflammation and extracellular matrix (ECM) degradation in CHON-001 cells. Additionally, circ_0001846 participated in IL-1β-induced chondrocyte cell damage by sponging miR-149-5p. MiR-149-5p mediated IL-1β-induced chondrocyte cell dysfunction by targeting WNT5B. Furthermore, circ_0001846 secretion was mediated by exosomes in IL-1β-treated CHON-001 cells. CONCLUSION Exosome-mediated transfer of circ_0001846 modulated IL-1β-induced chondrocyte cell damage by miR-149-5p/WNT5B axis, providing a novel avenue for the therapy of OA.
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Studies on the Role of circRNAs in Osteoarthritis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:8231414. [PMID: 34527744 PMCID: PMC8437644 DOI: 10.1155/2021/8231414] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/31/2021] [Accepted: 08/17/2021] [Indexed: 12/30/2022]
Abstract
Objective Provide a reference to elucidate the mechanism of circRNAs regulating osteoarthritis (OA) and the clinical treatment. Methods Herein, articles about circRNAs (hsa-circ) and osteoarthritis in the recent 5 years have been reviewed and the differential expression and regulatory effect of circRNAs in OA deduced. Based on these conclusions and Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the acquired circRNAs, the potential functions and interactions of circRNAs in OA and the involved signaling pathways are discussed. Results A total of 33 studies meeting the inclusion criteria were included in this study, and 27 circRNAs were upregulated and 8 circRNAs were downregulated in OA. A total of 31 circRNAs were finally included in the PPI, GO, and KEGG analyses. From PPI, 12 map nodes and 7 map edges were interrelated. VWF had the biggest node and edge size. From GO, VWF showed a majority of the functions. From KEGG, circRNAs are enriched in PI3K/AKT, human papillomavirus infection (HPI), and focal adhesion (FA) pathways, and VWF was involved in major pathways. Conclusion We found that most articles about circRNAs regulating OA in the recent 5 years focused on the mechanism, especially the absorption effect of circ-miRNA as sponges in the recent 2 years, while most of the articles about their functions addressed ECM and PI3K, AKT, and mTOR signaling pathways. Future studies might focus on the functions of circRNAs, and circRNA VWF, with preferable functions, interactions, and involvement, can be used as a biological indicator to detect OA in clinical practice.
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Tan L, Xie Y, Yuan Y, Hu K. LncRNA GAS5 as miR-26a-5p Sponge Regulates the PTEN/PI3K/Akt Axis and Affects Extracellular Matrix Synthesis in Degenerative Nucleus Pulposus Cells in vitro. Front Neurol 2021; 12:653341. [PMID: 34413821 PMCID: PMC8369364 DOI: 10.3389/fneur.2021.653341] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 06/30/2021] [Indexed: 12/23/2022] Open
Abstract
The role of lncRNA growth arrest specific 5 (GAS5) in degenerative nucleus pulposus cell (NPC) apoptosis has been reported, but the mechanism of GAS5 in extracellular matrix (ECM) synthesis in intervertebral disc degeneration (IDD) remains unknown. We aimed to investigate the mechanism of GAS5 in ECM synthesis in degenerative NPCs. GAS5 expression was measured in degenerative NPCs (CP-H170) and normal NPCs (CP-H097). siRNA-mediated GAS5 knockdown was transfected to NPCs to detect cell viability and the expression of ECM-related genes (Collagen II, aggrecan, Collagen I, and MMP-3). Subcellular localization of GAS5 was analyzed. The downstream gene and pathway of GAS5 in degenerative NPCs were explored. As our results indicated, lncRNA GAS5 was upregulated in degenerative NPCs. Silencing GAS5 improved the viability of degenerative NPCs and increased ECM synthesis. GAS5 was mainly located in the cytoplasm of NPCs. LncRNA GAS5 sponged miR-26a-5p to regulate PTEN. Overexpression of miR-26a-5p promoted ECM synthesis in degenerative NPCs. Akt inhibitor LY294002 reversed the promotion of silencing GAS5 on ECM synthesis of degenerative NPCs. In conclusion, lncRNA GAS5 sponged miR-26a-5p to upregulate PTEN and inhibit the PI3K/Akt pathway, thus inhibiting ECM synthesis of degenerative NPCs.
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Affiliation(s)
- Liang Tan
- Department of Spine Surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College, Central South University, Zhuzhou, China
| | - Yifang Xie
- Department of Spine Surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College, Central South University, Zhuzhou, China
| | - Ye Yuan
- Department of Spine Surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College, Central South University, Zhuzhou, China
| | - Kai Hu
- Department of Spine Surgery, The Affiliated Zhuzhou Hospital of Xiangya Medical College, Central South University, Zhuzhou, China
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Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction. Aging (Albany NY) 2021; 13:20383-20394. [PMID: 34413269 PMCID: PMC8436948 DOI: 10.18632/aging.203420] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 07/17/2021] [Indexed: 11/25/2022]
Abstract
Mechanical, metabolic, inflammatory, and immune factors contribute to the development of osteoarthritis (OA), a joint disease characterized by cartilage destruction. The circular RNA (circRNA) hsa_circ_0134111 is upregulated in the cartilage of OA patients; however, its potential role in OA pathogenesis and progression remains unexplored. In this study, the effects of hsa_circ_0134111 knockdown were evaluated in primary human chondrocytes treated with IL-1β to simulate OA, as well as in a rat model of OA. Hsa_circ_0134111 expression was upregulated in IL-1β-stimulated chondrocytes. CCK-8 and flow cytometry assays showed that hsa_circ_0134111 knockdown reversed IL-1β-induced cell decline by inhibiting apoptosis. Following prediction analysis of circRNA and miRNA targets, dual-luciferase reporter and silencing/overexpression assays suggested that a regulatory network composed of hsa_circ_0134111, miR-224-5p, and CCL1 modulates IL-1β-mediated OA-like effects in chondrocytes. Accordingly, CCL1 overexpression abrogated the prosurvival effects of hsa_circ_0134111 knockdown in vitro. Moreover, hsa_circ_0134111 silencing in vivo alleviated cartilage destruction in an OA rat model, decreased IL-6 and TNF-α levels in synovial fluid, and downregulated CCL1 expression in the affected joints. These results suggest that hsa_circ_0134111 contributes to OA development by binding to miR-224-5p, thereby releasing the inhibition that miR-224-5p exerts over CCL1.
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Zhang Z, Yang B, Zhou S, Wu J. CircRNA circ_SEC24A upregulates DNMT3A expression by sponging miR-26b-5p to aggravate osteoarthritis progression. Int Immunopharmacol 2021; 99:107957. [PMID: 34325283 DOI: 10.1016/j.intimp.2021.107957] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 06/30/2021] [Accepted: 07/01/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by degeneration and injury of articular cartilage. Circular RNA_SEC24A (circ_SEC24A; circBase ID: hsa_circ_0005105) is upregulated and promotes multiple tumor processes. However, its role in OA progression remained mostly unknown. METHODS Quantitative real-time PCR (qRT-PCR) was used to detect the RNA expression of circ_SEC24A, miR-26b-5p and DNA methyltransferase 3 alpha (DNMT3A). Cell proliferation was verified by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Flow cytometry was used to detect apoptosis. Western blot was used to detect protein expression of DNMT3A, proliferating cell nuclear antigen (PCNA), extracellular matrix (ECM) proteins (Collagen II and Aggrecan), and ECM degrading enzymes (matrix metalloproteinase-13 [MMP13] and metallopeptidase with thrombospondin type 1 motif 5 [ADAMTS5]). The target relationship between miR-26b-5p and circ_SEC24A or DNMT3A was predicted by Statbase3.0 or TargetScan and confirmed by dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation. RESULTS Circ_SEC24A was upregulated in osteoarthritic cartilage tissues and IL-1β-induced chondrocytes, accompanying with miR-26b-5p downregulation and DNMT3A upregulation. Circ_SEC24A expression was resistant to RNase R digestion and mainly expressed in the cytoplasm. Interfering circ_SEC24A abolished IL-1β-induced effects on proliferation inhibition, apoptosis, and ECM degradation in chondrocytes, but overexpressing circ_SEC24A had the opposite effects. Inhibiting miR-26b-5p counteracted but upregulating miR-26a-5p mimicked the functions of circ_SEC24A silencing. Reinforcing DNMT3A reversed miR-26b-5p overexpression's role in IL-1β-induced chondrocytes. Mechanically, circ_SEC24A and DNMT3A were competitive endogenous RNAs (ceRNAs) for miR-26b-5p. CONCLUSION Circ_SEC24A was a promoting factor for IL-1β-induced OA progression via circ_SEC24A/miR-26b-5p/DNMT3A ceRNA axis.
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Affiliation(s)
- Zhongqiang Zhang
- Department of Joint Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang City, Hunan 421002, China
| | - Bo Yang
- Department of Joint Surgery, Affiliated Nanhua Hospital, University of South China, Hengyang City, Hunan 421002, China
| | - Shuping Zhou
- Department of Sports Medicine, Affiliated Nanhua Hospital, University of South China, Hengyang City, Hunan 421002, China
| | - Junxing Wu
- Department of Sports Medicine, Affiliated Nanhua Hospital, University of South China, Hengyang City, Hunan 421002, China.
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Ji F, Lang C, Gao P, Sun H. Knockdown of Circ_0000144 Suppresses Cell Proliferation, Migration and Invasion in Gastric Cancer Via Sponging MiR-217. J Microbiol Biotechnol 2021; 31:784-793. [PMID: 33958507 PMCID: PMC9705855 DOI: 10.4014/jmb.2102.02005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/23/2021] [Accepted: 05/03/2021] [Indexed: 12/15/2022]
Abstract
Previous studies have uncovered the role of circ_0000144 in various tumors. Here, we investigated the function and mechanism of circ_0000144 in gastric cancer (GC) progression. The expression of circ_0000144 in GC tissues and cells was detected through quantitative real-time polymerase chain reaction (qRT-PCR) method. Gain- and loss-of-function experiments including colony formation, wound healing and transwell assays were performed to examine the role of circ_0000144 in GC cells. Furthermore, western blot was conducted to determine the expressions of epithelial mesenchymal transition (EMT)-related proteins. The interaction between circ_0000144 and miR-217 was analyzed by bioinformatic analysis and luciferase reporter assays. The circ_0000144 expression was obviously upregulated in GC tissues and cells. Silencing of circ_0000144 inhibited cell proliferation, migration and invasion of GC cells, but ectopic expression of circ_0000144 showed the opposite results. Moreover, circ_0000144 sponged miR-217, and rescue assays revealed that silencing miR-217 expression reversed the inhibitory effect of circ_0000144 knockdown on the progress of GC. Our findings reveal that circ_0000144 inhibition suppresses GC cell proliferation, migration and invasion via absorbing miR-217, providing a new biomarker and potential therapeutic target for treatment of GC.
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Affiliation(s)
- Fengcun Ji
- Department of General Surgery, Sunshine Union Hospital, High-Tech District, Weifang 261000, P.R. China
| | - Chao Lang
- Department of General Surgery, Sunshine Union Hospital, High-Tech District, Weifang 261000, P.R. China
| | - Pengfei Gao
- Department of General Surgery, Sunshine Union Hospital, High-Tech District, Weifang 261000, P.R. China
| | - Huanle Sun
- Department of General Surgery, Sunshine Union Hospital, High-Tech District, Weifang 261000, P.R. China,Corresponding author E-mail:
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Liu Y, Li Q, Gao Z, Lei F, Gao X. Circ-SPG11 knockdown hampers IL-1β-induced osteoarthritis progression via targeting miR-337-3p/ADAMTS5. J Orthop Surg Res 2021; 16:392. [PMID: 34140036 PMCID: PMC8212518 DOI: 10.1186/s13018-021-02526-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 06/06/2021] [Indexed: 11/10/2022] Open
Abstract
Background Osteoarthritis (OA) is responsible for the impotent disability in old people. Circular RNA (circRNA) has been reported to be related to the development of diseases. The lack of research on the role of circRNA spastic paraplegia 11 (circ-SPG11) results in conducting this study. Methods The expression of circ-SPG11, microRNA-337-3p (miR-337-3p), and aggrecanases like a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to measure the protein expression of extracellular matrix (ECM) degradation-related markers and ADAMTS5. Ribonuclease R (RNase R) was applied to test the stability of circ-SPG11 in CHON-001 cells. The viability, apoptosis, TNF-α and IL-6 production were determined by cell counting kit-8 (CCK-8) assay, flow cytometry assay, and enzyme-linked immunosorbent assay (ELISA), respectively. Meanwhile, the interaction between miR-337-3p and circ-SPG11 or ADAMTS5 was respectively predicted by Circinteractome or Starbase2.0, which was further verified by dual-luciferase reporter system and RNA binding protein immunoprecipitation (RIP) assay. Results Circ-SPG11 and ADAMTS5 were upregulated and miR-337-3p was downregulated in OA tissues and OA model cells. Circ-SPG11 knockdown allayed interleukin 1β (IL-1β)-induced restraint in viability and promotion in apoptosis, TNF-α, and IL-6 generation and ECM degradation in CHON-001 cells. Anti-miR-337-3p or ADAMTS5 overexpression correspondingly reversed si-circ-SPG11 or miR-337-3p overexpression-mediated facilitation in viability, and inhibition in apoptosis, TNF-α and IL-6 generation and ECM degradation in OA model cells. Moreover, anti-miR-337-3p ameliorated si-circ-SPG11-mediated inhibition in ADAMTS5 mRNA and protein expression in OA model cells. Conclusion Circ-SPG11 facilitated OA development via regulating miR-337-3p/ADAMTS5 axis. This finding might contribute to the improvement of OA therapy.
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Affiliation(s)
- Yongqiang Liu
- Department of Orthopedics, Shijiazhuang People's Hospital, No. 365 Jianhua South Road, Shijiazhang, Hebei, 050000, People's Republic of China
| | - Qian Li
- Department of Orthopedics, Shijiazhuang People's Hospital, No. 365 Jianhua South Road, Shijiazhang, Hebei, 050000, People's Republic of China
| | - Zhida Gao
- Department of Orthopedics, Shijiazhuang People's Hospital, No. 365 Jianhua South Road, Shijiazhang, Hebei, 050000, People's Republic of China
| | - Fang Lei
- Department of Orthopedics, Shijiazhuang People's Hospital, No. 365 Jianhua South Road, Shijiazhang, Hebei, 050000, People's Republic of China.
| | - Xuefeng Gao
- Department of Orthopedics, Shijiazhuang People's Hospital, No. 365 Jianhua South Road, Shijiazhang, Hebei, 050000, People's Republic of China
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Abstract
Acute kidney injury (AKI) is an independent risk factor for the increased risk of death in patients with sepsis. In the current study, we first investigated the expression of circMTO1 in sepsis-induced AKI, and the underlying mechanism was further elucidated. The results showed that circMTO1 expression level was significantly decreased in serums and kidney tissues of US rats and RMCs treated with LPS. Besides, circMTO1 overexpression promoted cell viability, suppressed cell apoptosis and cytokines production of LPS-treated RMCs. Bioinformatics analysis showed that circMTO1 served as a sponge for miR-337. Furthermore, circMTO1 could inhibit the expression of KLF6. Altogether, our study first reported that circMTO1 expression was decreased in sepsis-induced AKI rat models and RMCs treated with LPS. CircMTO1 overexpression could attenuate AKI development by sponging miR-337 and regulating KLF6 expression, which may provide new ideas for evaluation the pathogenesis and the treatment of sepsis-induced AKI.
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Affiliation(s)
- Chuan-Chuan Shi
- Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Lu-Yan Pan
- Henan Health Cadre College, Zhengzhou, 450000, Henan, China
| | - Zhi-Yong Peng
- Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Jian-Guo Li
- Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
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Exosomal circ-BRWD1 contributes to osteoarthritis development through the modulation of miR-1277/TRAF6 axis. Arthritis Res Ther 2021; 23:159. [PMID: 34082824 PMCID: PMC8173917 DOI: 10.1186/s13075-021-02541-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 05/21/2021] [Indexed: 11/16/2022] Open
Abstract
Background Circular RNAs (circRNAs) can act as vital players in osteoarthritis (OA). However, the roles of circRNAs in OA remain obscure. Herein, we explored the roles of exosomal circRNA bromodomain and WD repeat domain containing 1(circ-BRWD1) in OA pathology. Methods In vitro model of OA was constructed by treating CHON-001 cells with interleukin-1β (IL-1β). Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used for circ-BRWD1, BRWD, miR-1277, and TNF receptor-associated factor 6 (TRAF6) levels. RNase R assay was conducted for the feature of circ-BRWD1. Transmission electron microscopy (TEM) was employed to analyze the morphology of exosomes. Western blot assay was performed for protein levels. Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis, and 5-Ethynyl-2′-deoxyuridine (EDU) assay were adopted for cell viability, apoptosis, and proliferation, respectively. Enzyme-linked immunosorbent assay (ELISA) was carried out for the concentrations of interleukin-6 (IL-6) and interleukin-8 (IL-8). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to analyze the interaction between miR-1277 and circ-BRWD1 or TRAF6. Results Circ-BRWD1 was increased in OA cartilage tissues, IL-1β-treated CHON-001 cells, and the exosomes derived from IL-1β-treated CHON-001 cells. Exosome treatment elevated circ-BRWD1 level, while exosome blocker reduced circ-BRWD1 level in IL-1β-treated CHON-001 cells. Silencing of circ-BRWD1 promoted cell viability and proliferation and repressed apoptosis, inflammation, and extracellular matrix (ECM) degradation in IL-1β-stimulated CHON-001 cells. For mechanism analysis, circ-BRWD1 could serve as the sponge for miR-1277 to positively regulate TRAF6 expression. Moreover, miR-1277 inhibition ameliorated the effects of circ-BRWD1 knockdown on IL-1β-mediated CHON-001 cell damage. Additionally, miR-1277 overexpression relieved IL-1β-induced CHON-001 cell injury, while TRAF6 elevation restored the impact. Conclusion Exosomal circ-BRWD1 promoted IL-1β-induced CHON-001 cell progression by regulating miR-1277/TRAF6 axis.
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Li X, Jiang W, Zhong Y, Wu L, Sun G, Wang H, Tao J, Li Z. Advances of circular RNAs in thyroid cancer: An overview. Biomed Pharmacother 2021; 140:111706. [PMID: 34004512 DOI: 10.1016/j.biopha.2021.111706] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 05/03/2021] [Accepted: 05/05/2021] [Indexed: 12/19/2022] Open
Abstract
Circular RNA (circRNA) is a general term for a type of single-stranded RNAs, they are primarily generated via exon back-splice process in precursor mRNAs (pre-mRNAs). circRNAs refer to an emerging type of endogeneity-correlated closed molecules of RNA in a covalent manner. They mainly function as microRNA sponges, protein brackets, and regulatory element in transcription and splicing process. Recently, it has also starting been noticed that they serve as extraordinary models involved in polypeptides producing process. Although circRNAs have been extensively studied, their function in thyroid carcinoma is still lacking. Thus, we present the latest advances in circRNA research and summarize their fundamental rules of regulating process as well as the mechanism. More importantly, We mainly review the role and mechanism of circRNA in thyroid cancer, which provides an emerging perspective and theoretically supports the treatment of thyroid cancer.
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Affiliation(s)
- Xiao Li
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Wei Jiang
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yi Zhong
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Liangliang Wu
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Guoqiang Sun
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hanjin Wang
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Jing Tao
- Department of General Surgery, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Zhouxiao Li
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Pettenkoferstraße 8a, 80336, Munich, Germany.
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