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Sanz-Rubio D, Martín-Burriel I, Rodríguez J, Marín-Oto M, Khalyfa A, Sánchez-de-la-Torre M, Gozal D, Marin JM. Circulating Exosomal MicroRNAs and Subclinical Atherosclerosis in Obstructive Sleep Apnea. Arch Bronconeumol 2025; 61:235-238. [PMID: 39741042 DOI: 10.1016/j.arbres.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/11/2024] [Accepted: 12/12/2024] [Indexed: 01/02/2025]
Affiliation(s)
- David Sanz-Rubio
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain.
| | - Inmaculada Martín-Burriel
- Laboratorio de Genética Bioquímica (LAGENBIO), Instituto Agroalimentario de Aragón IA2 (UNIZAR-CITA), Instituto de Investigación Sanitaria de Aragón (IISAragón), Universidad de Zaragoza, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNed), Madrid, Spain
| | - Jorge Rodríguez
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain
| | - Marta Marín-Oto
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain
| | - Abdelnaby Khalyfa
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Manuel Sánchez-de-la-Torre
- Group of Precision Medicine in Chronic Diseases, Hospital Nacional de Parapléjicos, IDISCAM, Department of Nursing, Physiotherapy and Occupational Therapy, Faculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERes), Madrid, Spain
| | - David Gozal
- Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Jose M Marin
- Precision Medicine in Respiratory Diseases Group, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISAragón), Zaragoza, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERes), Madrid, Spain; Respiratory Service, Hospital Universitario Miguel Servet, University of Zaragoza, Zaragoza, Spain
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Schiavello M, Bosco O, Vizio B, Sciarrillo A, Pensa A, Pivetta E, Morello F, Risso D, Montrucchio G, Mariano F, Lupia E. Profiling of miRNAs Contained in Circulating Extracellular Vesicles and Associated with Sepsis Development in Burn Patients: A Proof-of-Concept Study. Int J Mol Sci 2025; 26:1844. [PMID: 40076471 PMCID: PMC11899136 DOI: 10.3390/ijms26051844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Sepsis is the leading cause of mortality in patients with burn injuries and it may represent, in these patients, a real diagnostic challenge. Here we studied the profile of miRNAs contained in extracellular vesicles (EVs) (EV-miRNAs) isolated from plasma from burn patients complicated by sepsis at admission and 7 days later. We enrolled 28 burn patients, 18 with (Burn Septic Patients-BSPs) and 10 without (Burn non-Septic Patients-BnSPs) sepsis. Ten healthy subjects (HSs) were used as additional controls. After EV isolation by charge precipitation and miRNA extraction, we proceeded with a two-phase approach. Through a first screening phase, we identified 178 miRNAs differentially expressed in BSPs compared to HSs. Among these, by a validation phase based on qRT-PCR, we found that miR-483-5p, miR-193a-5p, and miR-188-3p were increased in the BSPs compared to the BnSPs and HSs. Upon ROC analysis, all three miRNAs showed a good accuracy in differentiating BSPs from BnSPs, especially miR-483-5p (AUC = 0.955, p-value = 0.001). Moreover, we found 173 miRNAs differentially expressed in BSPs after 7 days from enrollment compared to T0, among whose miR-1-3p, miR-34a-3p, and miR-193a-5p decreased in BSPs after 7 days, in parallel with a decrease in SOFA scores. Finally, the other two miRNAs, miR-34a-3p and miR-193a-5p, positively correlated with the SOFA score. In conclusion, we identified several miRNAs-namely miR-483-5p, miR-193a-5p, and miR-188-3p-with potential clinical utility as diagnostic biomarkers in a heterogeneous population of burn patients at high risk of developing sepsis. Moreover, we found some miRNAs (miR-1-3p, miR-34a-3p, and miR-193a-5p) that vary according to the course of sepsis and others (miR-34a-3p and miR-193a-5p) that are associated with its clinical severity.
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Affiliation(s)
- Martina Schiavello
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
| | - Ornella Bosco
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
| | - Barbara Vizio
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
| | - Alberto Sciarrillo
- Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy; (A.S.); (A.P.); (D.R.)
| | - Anna Pensa
- Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy; (A.S.); (A.P.); (D.R.)
| | - Emanuele Pivetta
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
| | - Fulvio Morello
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
| | - Daniela Risso
- Plastic Surgery and Burn Center, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, 10126 Turin, Italy; (A.S.); (A.P.); (D.R.)
| | - Giuseppe Montrucchio
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
| | - Filippo Mariano
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
- Nephrology, Dialysis and Transplantation Unit, City of Health and Science, CTO Hospital, 10126 Turin, Italy
| | - Enrico Lupia
- Department of Medical Science, University of Turin, 10126 Turin, Italy; (M.S.); (O.B.); (B.V.); (E.P.); (F.M.); (F.M.); (E.L.)
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Tong Z, Xu X, Shen C, Yang D, Li Y, Li Q, Yang W, Xu F, Wu Z, Zhou L, Zhan C, Mao H. All-in-one multiple extracellular vesicle miRNA detection on a miniaturized digital microfluidic workstation. Biosens Bioelectron 2025; 270:116976. [PMID: 39591923 DOI: 10.1016/j.bios.2024.116976] [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: 09/16/2024] [Revised: 11/06/2024] [Accepted: 11/19/2024] [Indexed: 11/28/2024]
Abstract
Extracellular vesicles (EVs) and EV-derived microRNAs (EV-miRNAs) are emerging as promising circulating biomarkers for early detection of malignant tumors such as non-small cell lung cancer (NSCLC). However, utilization of the gold standard method of RNA detection, the reverse transcription - quantitative polymerase chain reaction (RT-qPCR), on EV-miRNAs is hindered by laborious sample purification requirements and time-consuming multi-step procedures. Herein, we propose and demonstrate a miniaturized digital microfluidic (DMF) workstation for all-in-one EV-miRNA detection based on RT-qPCR. In comparison with the previously reported DMF platform for EV isolation, the system further integrates parallel on-chip real-time PCR capability with a comparable detection sensitivity with in-vitro RT-qPCR (limit of detection = 2 copies/μL), realizing automated, miniaturized, and facile EV-miRNA detection. Meanwhile, major methodological improvements were made, including one-step stem-looped RT-qPCR for miRNAs with both high sensitivity and specificity, and a simplified DMF substrate rework strategy for cost-effectiveness. As a demonstration, the detection of NSCLC-related EV-miRNAs within 20 μL of plasma samples was implemented, indicating the potential applicability of the DMF workstation and its automated protocol on point-of-care diagnosis of a wide range of diseases.
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Affiliation(s)
- Zhaoduo Tong
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Xin Xu
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Chuanjie Shen
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Dawei Yang
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yan Li
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 200032, China
| | - Qiushi Li
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Weidong Yang
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Fangliang Xu
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Zhenhua Wu
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Lin Zhou
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Cheng Zhan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Hongju Mao
- State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
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Naranbat D, Herdes E, Tapinos N, Tripathi A. Review of microRNA detection workflows from liquid biopsy for disease diagnostics. Expert Rev Mol Med 2025; 27:e11. [PMID: 39911053 PMCID: PMC11879380 DOI: 10.1017/erm.2025.2] [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: 06/25/2024] [Revised: 12/04/2024] [Accepted: 01/13/2025] [Indexed: 02/07/2025]
Abstract
MicroRNAs have emerged as effective biomarkers in disease diagnostics, particularly cancer, due to their role as regulatory sequences. More recently, microRNAs have been detected in liquid biopsies, which hold immense potential for early disease diagnostics. This review comprehensively analyses distinct liquid biopsy microRNA detection methods validated with clinical samples. Each step in the microRNA detection workflow, including sample collection, RNA isolation, processing, and detection of target microRNAs, has been thoroughly assessed. The review discusses the advantages and limitations of established and novel techniques in microRNA detection workflows, discussing their diagnostic capabilities and potential for future implementation at scale.
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Affiliation(s)
- Dulguunnaran Naranbat
- Center for Biomedical Engineering, School of Engineering, Brown University, Providence, RI, USA
| | - Emilia Herdes
- Center for Biomedical Engineering, School of Engineering, Brown University, Providence, RI, USA
| | - Nikos Tapinos
- Warren Alpert Medical School, Brown University, Providence, RI, USA
- Department of Neurosurgery, Rhode Island Hospital, Providence, RI, USA
| | - Anubhav Tripathi
- Center for Biomedical Engineering, School of Engineering, Brown University, Providence, RI, USA
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Zhang S, Yang Y, Wang D, Yang X, Cai Y, Shui C, Yang R, Tian W, Li C. Exploring exosomes: novel diagnostic and therapeutic frontiers in thyroid cancer. Front Pharmacol 2024; 15:1431581. [PMID: 39584141 PMCID: PMC11581896 DOI: 10.3389/fphar.2024.1431581] [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: 05/12/2024] [Accepted: 10/25/2024] [Indexed: 11/26/2024] Open
Abstract
In recent years, the incidence of thyroid cancer has surged globally, posing significant challenges in its diagnosis, treatment, and prognosis. Exosomes, as a class of extracellular vesicles, are secreted by nearly all cell types and encapsulate a variety of nucleic acids and proteins reflective of their cell of origin, thereby facilitating critical intercellular communication. Recent advancements in understanding these exosomes have catalyzed their application in oncology, particularly through uncovering their roles in the pathogenesis, diagnosis, and therapy of cancers. Notably, the latest literature highlights the integral role of exosomes in refining diagnostic techniques, enhancing targeted therapies, optimizing radiotherapy outcomes, and advancing immunotherapeutic approaches in thyroid cancer management. This review provides a current synthesis of the implications of exosomes in thyroid cancer tumorigenesis and progression, as well as their emerging applications in diagnosis and treatment strategies. Furthermore, we discuss the profound clinical potential of exosome-based interventions in managing thyroid cancer, serving as a foundational reference for future therapeutic developments.
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Affiliation(s)
- Sicheng Zhang
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Yan Yang
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Dianri Wang
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Xueting Yang
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Yongcong Cai
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Chunyan Shui
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
| | - Ruoyi Yang
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
- Department of Oral and Maxillofacial Surgery, Guizhou Medical University, Guiyang, China
| | - Wen Tian
- Department of General Surgery, Chinese People’s Liberation Army General Hospital, Beijing, China
| | - Chao Li
- Department of Head and Neck Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China
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Li S, Cheng F, Zhang Z, Xu R, Shi H, Yan Y. The role of hepatocyte-derived extracellular vesicles in liver and extrahepatic diseases. Biomed Pharmacother 2024; 180:117502. [PMID: 39357327 DOI: 10.1016/j.biopha.2024.117502] [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: 07/21/2024] [Revised: 09/09/2024] [Accepted: 09/19/2024] [Indexed: 10/04/2024] Open
Abstract
Extracellular vesicles (EVs) are vesicle-like bodies with a double membrane structure that are released from the cell membrane or secreted by cells into the extracellular environment. These include exosomes, microvesicles, and apoptotic bodies. There is growing evidence indicating that the composition of liver cell contents changes following injury. The quantity of EVs and the biologically active substances they carry vary depending on the condition of the liver cells. Hepatocytes utilize EVs to modulate the functions of different liver cells and transfer them to distant organs via the systemic circulation, thereby playing a crucial role in intercellular communication. This review provides a concise overview of the research on the effects and potential mechanisms of hepatocyte-derived EVs (Hep-EVs) on liver diseases and extrahepatic diseases under different physiological and pathological conditions. Common liver diseases discussed include non-alcoholic fatty liver disease (NAFLD), viral hepatitis, alcoholic liver disease, drug-induced liver damage, and liver cancer. Given that NAFLD is the most prevalent chronic liver disease globally, this review particularly highlights the use of hepatocyte-derived EVs in NAFLD for disease progression, diagnosis, and treatment.
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Affiliation(s)
- Shihui Li
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China; Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Fang Cheng
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China; Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Zhuan Zhang
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China; Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Ruizi Xu
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China; Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China
| | - Honglei Shi
- Wujin Hospital Affiliated With Jiangsu University, Changzhou Wujin People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213004, China; Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, Wujin Hospital Affiliated with Jiangsu University (Wujin Clinical College of Xuzhou Medical University), Changzhou 213017, China; Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Changzhou 213017, China.
| | - Yongmin Yan
- Department of Laboratory Medicine, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China; Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, Wujin Hospital Affiliated with Jiangsu University (Wujin Clinical College of Xuzhou Medical University), Changzhou 213017, China; Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Changzhou 213017, China.
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Wei L, Liu S, Xie Z, Tang G, Lei X, Yang X. The interaction between m6A modification and noncoding RNA in tumor microenvironment on cancer progression. Int Immunopharmacol 2024; 140:112824. [PMID: 39116490 DOI: 10.1016/j.intimp.2024.112824] [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: 06/12/2024] [Revised: 07/21/2024] [Accepted: 07/25/2024] [Indexed: 08/10/2024]
Abstract
Cancer development is thought to be closely related to aberrant epigenetic regulation, aberrant expression of specific non-coding RNAs (ncRNAs), and tumor microenvironment (TME). The m6A methylation is one of the most abundant RNA modifications found in eukaryotes, and it can determine the fate of RNA at the post-transcriptional level through a variety of mechanisms, which affects important biological processes in the organism. The m6A methylation modification is involved in RNA processing, regulation of RNA nuclear export or localisation, RNA degradation and RNA translation. This process affects the function of mRNAs and ncRNAs, thereby influencing the biological processes of cancer cells. TME accelerates and promotes cancer generation and progression during tumor development. The m6A methylation interacting with ncRNAs is closely linked to TME formation. Mutual regulation and interactions between m6A methylation and ncRNAs in TME create complex networks and mediate the progression of various cancers. In this review, we will focus on the interactions between m6A modifications and ncRNAs in TME, summarising the molecular mechanisms by which m6A interacts with ncRNAs to affect TME and their roles in the development of different cancers. This work will help to deepen our understanding of tumourigenesis and further explore new targets for cancer therapy.
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Affiliation(s)
- Liushan Wei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China
| | - Shun Liu
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China
| | - Zhizhong Xie
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China
| | - Guotao Tang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China
| | - Xiaoyong Lei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, People's Republic of China.
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van Rensburg DJ, Womersley JS, Martin L, Seedat S, Hemmings SMJ. Differential microRNA expression in adolescent anxiety proneness. Eur J Neurosci 2024; 60:5680-5693. [PMID: 39189635 DOI: 10.1111/ejn.16523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 07/29/2024] [Accepted: 08/14/2024] [Indexed: 08/28/2024]
Abstract
Biological mechanisms underlying anxiety proneness (AP), the tendency to react fearfully to stressors due to the belief that experiencing anxiety has harmful consequences, remain unclear. Epigenetic mechanisms, such as microRNAs (small, non-coding RNAs 19-20 nucleotides long), may be contributory. This study investigated AP-associated differences in microRNA expression among South African adolescents with variable exposure to childhood trauma (CT). AP was assessed using a composite score reflecting trait anxiety and anxiety sensitivity, while CT exposure was assessed with the Childhood Trauma Questionnaire. High-quality total RNA (n = 88) extracted from whole blood underwent microRNA-sequencing. Differential microRNA expression analysis was conducted with DESeq2 in R, messenger RNA target prediction analysis was performed using TargetScan and DIANA-microT, and the DIANA mirPATH tool was used for KEGG pathway analysis. The majority of participants were female (75.86%) with an average age of 15 (±1.19) years. MicroRNA expression analysis identified upregulation of hsa-miR-28-5p and downregulation of hsa-miR-502-3p and hsa-miR-500a-3p in high-AP individuals, irrespective of CT. Four KEGG pathways, each with ≥10% of their constituent genes predicted to be targets of the differentially expressed microRNAs, were identified and were enriched for genes involved in calcineurin and glutamate signalling. These findings suggest that epigenetically mediated effects on neuronal function contribute to the molecular aetiology of AP.
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Affiliation(s)
- Danièlle Jansen van Rensburg
- Division of Molecular Biology and Human Genetics, Department of Biomedical Science, Faculty of Medicine and Health Science, Stellenbosch University, Cape Town, South Africa
| | - Jacqueline Samantha Womersley
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Stellenbosch University/South African Medical Research Council Genomics of Brain Disorders Extramural Research Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Lindi Martin
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Soraya Seedat
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Stellenbosch University/South African Medical Research Council Genomics of Brain Disorders Extramural Research Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Sian Megan Joanna Hemmings
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
- Stellenbosch University/South African Medical Research Council Genomics of Brain Disorders Extramural Research Unit, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Chen NN, Zhou KF, Miao Z, Chen YX, Cui JX, Su SW. Exosomes regulate doxorubicin resistance in breast cancer via miR-34a-5p/NOTCH1. Mol Cell Probes 2024; 76:101964. [PMID: 38810840 DOI: 10.1016/j.mcp.2024.101964] [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: 03/22/2023] [Revised: 04/22/2024] [Accepted: 05/26/2024] [Indexed: 05/31/2024]
Abstract
Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.
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Affiliation(s)
- Nan-Nan Chen
- Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Ke-Fan Zhou
- Key Laboratory of Innovative Drug Research and Safety Evaluation, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Zhuang Miao
- Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Yun-Xia Chen
- Key Laboratory of Innovative Drug Research and Safety Evaluation, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, Hebei, China
| | - Jing-Xia Cui
- Key Laboratory of Innovative Drug Research and Safety Evaluation, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
| | - Su-Wen Su
- Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
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10
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de Lourdes Signorini-Souza I, Tureck LV, Batistela MS, Coutinho de Almeida R, Monteiro de Almeida S, Furtado-Alle L, Lehtonen Rodrigues Souza R. The potential of five c-miRNAs as serum biomarkers for Late-Onset Alzheimer's disease diagnosis: miR-10a-5p, miR-29b-2-5p, miR-125a-5p, miR-342-3p, and miR-708-5p. Brain Res 2024; 1841:149090. [PMID: 38880411 DOI: 10.1016/j.brainres.2024.149090] [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: 03/08/2024] [Revised: 05/29/2024] [Accepted: 06/13/2024] [Indexed: 06/18/2024]
Abstract
The nervous system is rich in miRNAs, indicating an important role of these molecules in regulating processes associated with cognition, memory, and others. Therefore, qualitative and quantitative imbalances involving such miRNAs may be involved in dementia contexts, including Late-Onset Alzheimer's Disease (LOAD). To test the viability of circulating miRNAs (c-miRNAs) as biomarkers for LOAD, we proceed accordingly to the following reasoning. The first stage was to discover and identify profile of c-miRNAs by RNA sequencing (RNA-Seq). For this purpose, blood serum samples were used from LOAD patients (n = 5) and cognitively healthy elderly control group (CTRL_CH) (n = 5), all over 70 years old. We identified seven c-miRNAs differentially expressed (p ≤ 0.05) in the serum of LOAD patients compared to CTRL_CH (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p, miR-380-5p and miR-340-3p). Of these, five (p ≤ 0.01) were selected for in silico analysis (miR-10a-5p; miR-29b-2-5p; miR-125a-5p; miR-342-3p, miR-708-5p), for which 44 relevant target genes were found regulated by these c-miRNAs and related to LOAD. Through the analysis of these target genes in databases, it was possible to observe that they have functions related to the development and progress of LOAD, directly or indirectly connecting the different Alzheimer's pathways. Thus, this work found five promising serum c-miRNAs as options for biomarkers contributing to LOAD diagnosis. Our study shows the complex network between these molecules and LOAD, supporting the relevance of studies using c-miRNAs in dementia contexts.
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Affiliation(s)
- Isadora de Lourdes Signorini-Souza
- Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990 Curitiba, Paraná State, Brazil
| | - Luciane Viater Tureck
- Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990 Curitiba, Paraná State, Brazil
| | - Meire Silva Batistela
- Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990 Curitiba, Paraná State, Brazil
| | - Rodrigo Coutinho de Almeida
- Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, LUMC, Leiden, the Netherlands
| | | | - Lupe Furtado-Alle
- Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990 Curitiba, Paraná State, Brazil
| | - Ricardo Lehtonen Rodrigues Souza
- Postgraduate Program in Genetics. Department of Genetics, Federal University of Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-990 Curitiba, Paraná State, Brazil.
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11
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Vahidi S, Agah S, Mirzajani E, Asghari Gharakhyli E, Norollahi SE, Rahbar Taramsari M, Babaei K, Samadani AA. microRNAs, oxidative stress, and genotoxicity as the main inducers in the pathobiology of cancer development. Horm Mol Biol Clin Investig 2024; 45:55-73. [PMID: 38507551 DOI: 10.1515/hmbci-2023-0012] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 03/06/2024] [Indexed: 03/22/2024]
Abstract
Cancer is one of the most serious leading causes of death in the world. Many eclectic factors are involved in cancer progression including genetic and epigenetic alongside environmental ones. In this account, the performance and fluctuations of microRNAs are significant in cancer diagnosis and treatment, particularly as diagnostic biomarkers in oncology. So, microRNAs manage and control the gene expression after transcription by mRNA degradation, or also they can inhibit their translation. Conspicuously, these molecular structures take part in controlling the cellular, physiological and pathological functions, which many of them can accomplish as tumor inhibitors or oncogenes. Relatively, Oxidative stress is defined as the inequality between the creation of reactive oxygen species (ROS) and the body's ability to detoxify the reactive mediators or repair the resulting injury. ROS and microRNAs have been recognized as main cancer promoters and possible treatment targets. Importantly, genotoxicity has been established as the primary reason for many diseases as well as several malignancies. The procedures have no obvious link with mutagenicity and influence the organization, accuracy of the information, or fragmentation of DNA. Conclusively, mutations in these patterns can lead to carcinogenesis. In this review article, we report the impressive and practical roles of microRNAs, oxidative stress, and genotoxicity in the pathobiology of cancer development in conjunction with their importance as reliable cancer biomarkers and their association with circulating miRNA, exosomes and exosomal miRNAs, RNA remodeling, DNA methylation, and other molecular elements in oncology.
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Affiliation(s)
- Sogand Vahidi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shahram Agah
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ebrahim Mirzajani
- Department of Biochemistry and Biophysics, School of Medicine, 37554 Guilan University of Medical Sciences , Rasht, Iran
| | | | - Seyedeh Elham Norollahi
- Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran
| | - Morteza Rahbar Taramsari
- Department of Forensic Medicine, School of Medicine, 37554 Guilan University of Medical Sciences , Rasht, Iran
| | - Kosar Babaei
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Ali Akbar Samadani
- Guilan Road Trauma Research Center, Trauma Institute, Guilan University of Medical Sciences, Rasht, Iran
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12
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Zablon F, Desai P, Dellinger K, Aravamudhan S. Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis. Adv Biol (Weinh) 2024; 8:e2300532. [PMID: 38258348 PMCID: PMC11198028 DOI: 10.1002/adbi.202300532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 12/26/2023] [Indexed: 01/24/2024]
Abstract
Breast cancer accounts for the highest cancer cases globally, with 12% of occurrences progressing to metastatic breast cancer with a low survival rate and limited effective early intervention strategies augmented by late diagnosis. Moreover, a low concentration of prognostic and predictive markers hinders disease monitoring. Circulating and exosomal microRNAs (miRNAs) have recently shown a considerable interplay in breast cancer, standing out as effective diagnostic and prognostic markers. The primary functions are as gene regulatory agents at the genetic and epigenetic levels. An array of dysregulated miRNAs stimulates cancer-promoting mechanisms, activating oncogenes and controlling tumor-suppressing genes and mechanisms. Exosomes are vastly studied extracellular vesicles, carrying, and transporting cargo, including noncoding RNAs with premier roles in oncogenesis. Translocation of miRNAs from the circulation to exosomes, with RNA-binding proteins in stress-induced conditions, has shown significant cooperation in function to promote breast cancer. This review examines cellular and exosomal miRNA biogenesis and loading, the clinical implications of their dysregulation, their function in diagnosis, prognosis, and prediction of breast cancer, and in regulating cancer signaling pathways. The influence of cellular and exosomal miRNAs presents clinical significance on breast cancer diagnosis, subtyping, staging, prediction, and disease monitoring during treatment, hence a potent marker for breast cancer.
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Affiliation(s)
- Faith Zablon
- Joint School of Nanoscience and Nanoengineering, North Carolina, A & T State University, 2904 E. Gate City Blvd, Greensboro, NC-27401
| | - Parth Desai
- University of North Carolina, Greensboro, 2904 E. Gate City Blvd, Greensboro, NC-27401
| | - Kristen Dellinger
- Joint School of Nanoscience and Nanoengineering, North Carolina, A & T State University, 2904 E. Gate City Blvd, Greensboro, NC-27401
| | - Shyam Aravamudhan
- Joint School of Nanoscience and Nanoengineering, North Carolina, A & T State University, 2904 E. Gate City Blvd, Greensboro, NC-27401
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13
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Kaurani L. Clinical Insights into MicroRNAs in Depression: Bridging Molecular Discoveries and Therapeutic Potential. Int J Mol Sci 2024; 25:2866. [PMID: 38474112 PMCID: PMC10931847 DOI: 10.3390/ijms25052866] [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: 01/31/2024] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/14/2024] Open
Abstract
Depression is a major contributor to the overall global burden of disease. The discovery of biomarkers for diagnosis or prediction of treatment responses and as therapeutic agents is a current priority. Previous studies have demonstrated the importance of short RNA molecules in the etiology of depression. The most extensively researched of these are microRNAs, a major component of cellular gene regulation and function. MicroRNAs function in a temporal and tissue-specific manner to regulate and modify the post-transcriptional expression of target mRNAs. They can also be shuttled as cargo of extracellular vesicles between the brain and the blood, thus informing about relevant mechanisms in the CNS through the periphery. In fact, studies have already shown that microRNAs identified peripherally are dysregulated in the pathological phenotypes seen in depression. Our article aims to review the existing evidence on microRNA dysregulation in depression and to summarize and evaluate the growing body of evidence for the use of microRNAs as a target for diagnostics and RNA-based therapies.
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Affiliation(s)
- Lalit Kaurani
- Department for Epigenetics and Systems Medicine in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), 37075 Göttingen, Germany
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14
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Sandau US, Wiedrick JT, McFarland TJ, Galasko DR, Fanning Z, Quinn JF, Saugstad JA. Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers. Sci Rep 2024; 14:2148. [PMID: 38272952 PMCID: PMC10810819 DOI: 10.1038/s41598-024-52681-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 01/18/2024] [Indexed: 01/27/2024] Open
Abstract
There is great interest in developing clinical biomarker assays that can aid in non-invasive diagnosis and/or monitoring of human diseases, such as cancer, cardiovascular disease, and neurological diseases. Yet little is known about the longitudinal stability of miRNAs in human plasma. Here we assessed the intraindividual longitudinal stability of miRNAs in plasma from healthy human adults, and the impact of common factors (e.g., hemolysis, age) that may confound miRNA data. We collected blood by venipuncture biweekly over a 3-month period from 22 research participants who had fasted overnight, isolated total RNA, then performed miRNA qPCR. Filtering and normalization of the qPCR data revealed amplification of 134 miRNAs, 74 of which had high test-retest reliability and low percentage level drift, meaning they were stable in an individual over the 3-month time period. We also determined that, of nuisance factors, hemolysis and tobacco use have the greatest impact on miRNA levels and variance. These findings support that many miRNAs show intraindividual longitudinal stability in plasma from healthy human adults, including some reported as candidate biomarkers for Alzheimer's disease.
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Affiliation(s)
- Ursula S Sandau
- Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Jack T Wiedrick
- Biostatistics and Design Program, Oregon Health and Science University, Portland, OR, USA
| | - Trevor J McFarland
- Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Douglas R Galasko
- Department of Neurosciences, University of California San Diego, La Jolla, CA, USA
| | - Zoe Fanning
- Department of Neurology, Oregon Health and Science University, Portland, OR, USA
| | - Joseph F Quinn
- Department of Neurology, Oregon Health and Science University, Portland, OR, USA
| | - Julie A Saugstad
- Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA.
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15
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Wang Y, Zou M, Zhao Y, Kabir MA, Peng X. Exosomal microRNA/miRNA Dysregulation in Respiratory Diseases: From Mycoplasma-Induced Respiratory Disease to COVID-19 and Beyond. Cells 2023; 12:2421. [PMID: 37830635 PMCID: PMC10571955 DOI: 10.3390/cells12192421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/26/2023] [Accepted: 10/03/2023] [Indexed: 10/14/2023] Open
Abstract
Respiratory diseases represent a significant economic and health burden worldwide, affecting millions of individuals each year in both human and animal populations. MicroRNAs (miRNAs) play crucial roles in gene expression regulation and are involved in various physiological and pathological processes. Exosomal miRNAs and cellular miRNAs have been identified as key regulators of several immune respiratory diseases, such as chronic respiratory diseases (CRD) caused by Mycoplasma gallisepticum (MG), Mycoplasma pneumoniae pneumonia (MMP) caused by the bacterium Mycoplasma pneumoniae, coronavirus disease 2019 (COVID-19), chronic obstructive pulmonary disease (COPD), asthma, and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Consequently, miRNAs seem to have the potential to serve as diagnostic biomarkers and therapeutic targets in respiratory diseases. In this review, we summarize the current understanding of the functional roles of miRNAs in the above several respiratory diseases and discuss the potential use of miRNAs as stable diagnostic biomarkers and therapeutic targets for several immune respiratory diseases, focusing on the identification of differentially expressed miRNAs and their targeting of various signaling pathways implicated in disease pathogenesis. Despite the progress made, unanswered questions and future research directions are discussed to facilitate personalized and targeted therapies for patients with these debilitating conditions.
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Affiliation(s)
| | | | | | | | - Xiuli Peng
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (Y.W.); (M.Z.); (Y.Z.); (M.A.K.)
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16
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Elabd WK, Elbakry MMM, Hassany M, Baki AA, Seoudi DM, El Azeem EMA. Evaluation of miRNA-7, miRNA-10 and miRNA-21 as diagnostic non-invasive biomarkers of hepatocellular carcinoma. Clin Exp Hepatol 2023; 9:221-227. [PMID: 37790691 PMCID: PMC10544064 DOI: 10.5114/ceh.2023.130547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 07/02/2023] [Indexed: 10/05/2023] Open
Abstract
Aim of the study Liver cancer (hepatocellular carcinoma - HCC) remains a serious health challenge; it is the fourth leading cause of death worldwide. Egypt ranks fifteenth worldwide and the third in Africa in terms of HCC burden. The present study aimed to assess some microRNAs (miRNAs) including miRNA-7, miRNA-10, and miRNA-21, serum markers such as cluster of differentiation-14 (CD-14) and transforming growth factor b1 (TGF-b1), and other biochemical parameters as non-invasive tools for HCC diagnosis. Material and methods The study included 100 participants divided into five groups: group I (20 normal subjects as a healthy group), group II (20 participants with chronic HCV infection but non-cirrhotic), group III (20 volunteers with chronic HCV infection and compensated cirrhosis), group IV (20 patients with chronic HCV infection and decompensated cirrhosis), and group V (20 participants with HCC). Levels of miR-7, miR-10, and miR-21 were evaluated using qRT-PCR. Serum ALT, AST, total bilirubin, total protein, albumin, PT, INR, and platelet count were determined. FIB-4 and APRI test levels were also calculated. CD-14 and TGF-β1 serum levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits. Results The expression levels of miR-21 followed by miR-10 showed high sensitivity and specificity in predicting HCC. Serum CD-14 and TGF-b1 levels were significantly increased in all patient groups. Conclusions From the study, it is concluded that the expression level of miR-21 has the highest sensitivity and specificity, followed by miR-10, which has high sensitivity and low specificity as non-invasive markers for HCC detection, while miR-7 exhibits high sensitivity and reasonable specificity in fibrosis detection.
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Affiliation(s)
| | | | - Mohamed Hassany
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Amin Abdel Baki
- National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
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17
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Zhang MH, Yuan YF, Liu LJ, Wei YX, Yin WY, Zheng LZY, Tang YY, Lv Z, Zhu F. Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:4706-4735. [PMID: 37664153 PMCID: PMC10473924 DOI: 10.3748/wjg.v29.i31.4706] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/29/2023] [Accepted: 08/01/2023] [Indexed: 08/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignancy with a high incidence and fatality rate worldwide. Hepatitis B virus (HBV) infection is one of the most important risk factors for its occurrence and development. Early detection of HBV-associated HCC (HBV-HCC) can improve clinical decision-making and patient outcomes. Biomarkers are extremely helpful, not only for early diagnosis, but also for the development of therapeutics. MicroRNAs (miRNAs), a subset of non-coding RNAs approximately 22 nucleotides in length, have increasingly attracted scientists' attention due to their potential utility as biomarkers for cancer detection and therapy. HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis. In this review, we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC. From a molecular standpoint, we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC. In the near future, miRNA-based diagnostic, prognostic, and therapeutic applications will make their way into the clinical routine.
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Affiliation(s)
- Ming-He Zhang
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yu-Feng Yuan
- Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Li-Juan Liu
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Yu-Xin Wei
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Wan-Yue Yin
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Lan-Zhuo-Yin Zheng
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Ying-Ying Tang
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
| | - Zhao Lv
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Fan Zhu
- State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, Hubei Province, China
- Hubei Province Key Laboratory of Allergy & Immunology, Wuhan University, Wuhan 430071, Hubei Province, China
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Li W, Wang Z, Jiang Z, Yan Y, Yao X, Pan Z, Chen L, Wang F, Wang M, Qin Z. MiR-3960 inhibits bladder cancer progression via targeting of DEXI. Biochem Biophys Res Commun 2023; 668:8-18. [PMID: 37230046 DOI: 10.1016/j.bbrc.2023.05.055] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 05/15/2023] [Indexed: 05/27/2023]
Abstract
PURPOSE MicroRNAs (miRNAs) are dominant cargo in exosomes and act as master regulators of cell function, inhibiting mRNA translation and affecting gene silencing. Some aspects of tissue-specific miRNA transport in bladder cancer (BC) and its role in cancer progression are not fully understood. MATERIALS AND METHODS A microarray was used to identify miRNAs in mouse bladder carcinoma cell line MB49 exosomes. Real-time reverse transcription polymerase chain reaction was used to examine the expression of miRNAs in BC and healthy donor serum. Western blotting and immunohistochemical staining were used to examine the expression of dexamethasone-induced protein (DEXI) in patients with BC. CRISPR-Cas 9 was used to knock out Dexi in MB49, and flow cytometry was performed to test cell proliferation ability and apoptosis under chemotherapy. Human BC organoid culture, miR-3960 transfection, and 293T-exosome-loaded miR-3960 delivery were used to analyze the effect of miR-3960 on BC progression. RESULTS The results showed that miR-3960 levels in BC tissue were positively correlated with patient survival time. Dexi was a major target of miR-3960. Dexi knockout inhibited MB49 cell proliferation and promoted cisplatin- and gemcitabine-induced apoptosis. Transfection of miR-3960 mimic inhibited DEXI expression and organoid growth. In parallel, 293T-exosome-loaded miR-3960 delivery and Dexi knockout significantly inhibited subcutaneous growth of MB49 cells in vivo. CONCLUSION Our results demonstrate the potential role of miR-3960-mediated inhibition of DEXI as a therapeutic strategy against BC.
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Affiliation(s)
- Wenqing Li
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
| | - Zihao Wang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Ziming Jiang
- Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Yan Yan
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Xiaohan Yao
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Zhenzhen Pan
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Lin Chen
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Fei Wang
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Ming Wang
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
| | - Zhihai Qin
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China; Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
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Song X, Chen Y, Chen X, Zhao X, Zou Y, Li L, Zhou X, Li M, Zhang D, Ye G, Jia R, Yin Z. Exosomes from tannic acid-stimulated macrophages accelerate wound healing through miR-221-3p mediated fibroblasts migration by targeting CDKN1b. Int J Biol Macromol 2023; 244:125088. [PMID: 37270133 DOI: 10.1016/j.ijbiomac.2023.125088] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/06/2023] [Accepted: 05/22/2023] [Indexed: 06/05/2023]
Abstract
Tannic acid (TA) and its extraction were traditionally used for treatment of traumatic bleeding in China, and in the previous study we have demonstrated that TA could accelerate cutaneous wound healing in rats. We attempted to decipher the mechanism of TA in promoting wound healing. In this study, we found that TA could enhance the growth of macrophages and inhibit the release of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8 and IL-10) through inhibition of NF-κB/JNK pathway. TA activated Erk1/2 pathway, leading to increased expressions of growth factors, bFGF and HGF. Scratch study revealed that TA did not directly regulate the migration function of fibroblasts, but could indirectly enhance fibroblasts migration by the supernatant of TA-treated macrophages. Transwell study further proved that TA stimulates macrophages to secrete exosomes enriched in miR-221-3p by activating the p53 signaling pathway, and the exosomes entered into the fibroblast cytoplasm and bound to 3'UTR of target gene CDKN1b which induced decreased expression level of CDKN1b, leading to promoting fibroblast migration. This study provided new insights into how TA accelerates wound healing in the inflammatory and proliferative phases of wound healing.
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Affiliation(s)
- Xu Song
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Yaqin Chen
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Xiangxiu Chen
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Xinghong Zhao
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Yuanfeng Zou
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Lixia Li
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Xun Zhou
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Mingyue Li
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Dongmei Zhang
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Gang Ye
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China
| | - Renyong Jia
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
| | - Zhongqiong Yin
- Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
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Săsăran MO, Bănescu C. Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence. Front Genet 2023; 14:1228482. [PMID: 37456668 PMCID: PMC10346860 DOI: 10.3389/fgene.2023.1228482] [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: 05/30/2023] [Accepted: 06/20/2023] [Indexed: 07/18/2023] Open
Abstract
MiRNAs are short, non-coding RNA molecules, which are involved in the regulation of gene expression and which play an important role in various biological processes, including inflammation and cell cycle regulation. The possibility of detecting their extracellular expression, within body fluids, represented the main background for their potential use as non-invasive biomarkers of various diseases. Salivary miRNAs particularly gained interest recently due to the facile collection of stimulated/unstimulated saliva and their stability among healthy subjects. Furthermore, miRNAs seem to represent biomarker candidates of gastrointestinal disorders, with miRNA-based therapeutics showing great potential in those conditions. This review aimed to highlight available evidence on the role of salivary miRNAs in different gastrointestinal conditions. Most salivary-based miRNA studies available in the literature that focused on pathologies of the gastrointestinal tract have so far been conducted on pancreatic cancer patients and delivered reliable results. A few studies also showed the diagnostic utility of salivary miRNAs in conditions such as esophagitis, esophageal cancer, colorectal cancer, or inflammatory bowel disease. Moreover, several authors showed that salivary miRNAs may confidently be used as biomarkers of gastric cancer, but the use of salivary miRNA candidates in gastric inflammation and pre-malignant lesions, essential stages of Correa's cascade, is still put into question. On the other hand, besides miRNAs, other salivary omics have shown biomarker potential in gastro-intestinal conditions. The limited available data suggest that salivary miRNAs may represent reliable biomarker candidates for gastrointestinal conditions. However, their diagnostic potential requires validation through future research, performed on larger cohorts.
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Affiliation(s)
- Maria Oana Săsăran
- Department of Pediatrics 3, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Târgu Mureș, Romania
| | - Claudia Bănescu
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Targu Mures, Romania
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21
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Sandokji I, Xu Y, Denburg M, Furth S, Abraham AG, Greenberg JH. Current and Novel Biomarkers of Progression Risk in Children with Chronic Kidney Disease. Nephron Clin Pract 2023; 148:1-10. [PMID: 37232009 PMCID: PMC10840447 DOI: 10.1159/000530918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 02/18/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND Due to the complexity of chronic kidney disease (CKD) pathophysiology, biomarkers representing different mechanistic pathways have been targeted for the study and development of novel biomarkers. The discovery of clinically useful CKD biomarkers would allow for the identification of those children at the highest risk of kidney function decline for timely interventions and enrollment in clinical trials. SUMMARY Glomerular filtration rate and proteinuria are traditional biomarkers to classify and prognosticate CKD progression in clinical practice but have several limitations. Over the recent decades, novel biomarkers have been identified from blood or urine with metabolomic screening studies, proteomic screening studies, and an improved knowledge of CKD pathophysiology. This review highlights promising biomarkers associated with the progression of CKD that could potentially serve as future prognostic markers in children with CKD. KEY MESSAGES Further studies are needed in children with CKD to validate putative biomarkers, particularly candidate proteins and metabolites, for improving clinical management.
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Affiliation(s)
- Ibrahim Sandokji
- Department of Pediatrics, Taibah University College of Medicine, Medina, Saudi Arabia,
| | - Yunwen Xu
- Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA
| | - Michelle Denburg
- Division of Nephrology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Susan Furth
- Division of Nephrology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Alison G Abraham
- Department of Epidemiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jason H Greenberg
- Department of Pediatrics, Section of Nephrology, Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, Connecticut, USA
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22
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Encarnación-Medina J, Godoy L, Matta J, Ortiz-Sánchez C. Identification of Exo-miRNAs: A Summary of the Efforts in Translational Studies Involving Triple-Negative Breast Cancer. Cells 2023; 12:cells12091339. [PMID: 37174739 PMCID: PMC10177092 DOI: 10.3390/cells12091339] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 04/19/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers (BC) in the US and its diagnosis is associated with poor survival outcomes. A better understanding of the disease etiology is crucial to identify target treatment options to improve patient outcomes. The role of exo-miRNAs in TNBC has been studied for more than two decades. Although some studies have identified exo-miR candidates in TNBC using clinical samples, consensus regarding exo-miR candidates has not been achieved. The purpose of this review is to gather information regarding exo-miR candidates reported in TNBC translational studies along with the techniques used to isolate and validate the potential targets. The techniques suggested in this review are based on the use of commercially available materials for research and clinical laboratories. We expect that the information included in this review can add additional value to the recent efforts in the development of a liquid biopsy to identify TNBC cases and further improve their survival outcomes.
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Affiliation(s)
- Jarline Encarnación-Medina
- Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00716-2347, Puerto Rico
| | - Lenin Godoy
- Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00716-2347, Puerto Rico
| | - Jaime Matta
- Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00716-2347, Puerto Rico
| | - Carmen Ortiz-Sánchez
- Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce 00716-2347, Puerto Rico
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Zhang Y, Lv X, Chen F, Fan Q, Liu Y, Wan Z, Nibaruta J, Lv J, Han X, Wu L, Wang H, Leng Y. Role of microRNAs in programmed cell death in renal diseases: A review. Medicine (Baltimore) 2023; 102:e33453. [PMID: 37058073 PMCID: PMC10101263 DOI: 10.1097/md.0000000000033453] [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: 02/13/2023] [Accepted: 03/15/2023] [Indexed: 04/15/2023] Open
Abstract
MicroRNAs (miRNAs) regulate gene expression involving kidney morphogenesis and cell proliferation, apoptosis, differentiation, migration, invasion, immune evasion, and extracellular matrix remodeling. Programmed cell death (PCD) is mediated and regulated by specific genes and a wealth of miRNAs, which participate in various pathological processes. Dysregulation of miRNAs can disrupt renal development and induce the onset and progression of various renal diseases. An in-depth understanding of how miRNAs regulate renal development and diseases is indispensable to comprehending how they can be used in new diagnostic and therapeutic approaches. However, the mechanisms are still insufficiently investigated. Hence, we review the current roles of miRNA-related signaling pathways and recent advances in PCD research and aim to display the potential crosstalk between miRNAs and PCD. The prospects of miRNAs as novel biomarkers and therapeutic targets are also described, which might provide some novel ideas for further studies.
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Affiliation(s)
- Yan Zhang
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Xinghua Lv
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Feng Chen
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Qian Fan
- Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Nankai University Affiliated Eye Hospital, Tianjin, China
- Nankai Eye Institute, Nankai University, Tianjin, China
- Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China
| | - Yongqiang Liu
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Zhanhai Wan
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Janvier Nibaruta
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Jipeng Lv
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Xuena Han
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
| | - Lin Wu
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Hao Wang
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Yufang Leng
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
- The First Clinical Medical College of Lanzhou University, Lanzhou, GanSu Province, China
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24
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Fan W, Pang H, Li X, Xie Z, Huang G, Zhou Z. Plasma-derived exosomal miRNAs as potentially novel biomarkers for latent autoimmune diabetes in adults. Diabetes Res Clin Pract 2023; 197:110570. [PMID: 36746199 DOI: 10.1016/j.diabres.2023.110570] [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: 11/16/2022] [Revised: 01/28/2023] [Accepted: 02/01/2023] [Indexed: 02/06/2023]
Abstract
AIM To characterize the exosomal miRNA profiles of latent autoimmune diabetes in adults (LADA) and evaluate the biomarker potential of selected miRNAs to distinguish LADA from type 2 diabetes (T2D). METHODS Plasma-derived exosomal miRNA expression profiles were measured in patients with LADA (N = 5) and control subjects (N = 5). Five differentially expressed miRNAs were selected to validate their expression levels and assess their diagnostic potential by quantitative real-time PCR (qRT-PCR) in a larger cohort. RESULTS Seventy-five differentially expressed plasma-derived exosomal miRNAs were identified in LADA patients compared to healthy subjects. The expression levels of three exosomal miRNAs (hsa-miR-146a-5p, hsa-miR-223-3p and hsa-miR-21-5p) were significantly different between the LADA group and the T2D group. The three miRNAs exhibited areas under the receiver operating characteristic curves of 0.978, 0.96 and 0.809, respectively. CONCLUSIONS This study uncovers the miRNA profiles of plasma-derived exosomes from LADA patients and identifies exosomal miRNAs as potential biomarkers to discriminate LADA from T2D for the first time. Our data demonstrate the function of exosomal miRNAs in the development of LADA and contribute to an in-depth understanding of the precise mechanisms underlying the pathogenesis of LADA.
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Affiliation(s)
- Wenqi Fan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Haipeng Pang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiguo Xie
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Gan Huang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
| | - Zhiguang Zhou
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
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25
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Kumar P. miRNA dysregulation in traumatic brain injury and epilepsy: a systematic review to identify putative biomarkers for post-traumatic epilepsy. Metab Brain Dis 2023; 38:749-765. [PMID: 36715879 DOI: 10.1007/s11011-023-01172-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 01/18/2023] [Indexed: 01/31/2023]
Abstract
Traumatic brain injury (TBI) leads to post-traumatic epilepsy (PTE); hence, both TBI and PTE share various similar molecular mechanisms. MicroRNA (miRNA) is a small noncoding RNA that acts as a gene-silencing molecule. Notably, the dysregulation of miRNAs in various neurological diseases, including TBI and epilepsy, has been reported in several studies. However, studies on commonly dysregulated miRNAs and the regulation of shared pathways in both TBI and epilepsy that can identify potential biomarkers of PTE are still lacking. This systematic review covers the peer-review publications of TBI and database studies of epilepsy-dysregulated miRNAs of clinical studies. For TBI, 290 research articles were identified after screening, and 12 provided data for dysregulated miRNAs in humans. The compiled data suggest that 85 and 222 miRNAs are consecutively dysregulated in TBI and epilepsy. In both, 10 miRNAs were found to be commonly dysregulated, implying that they are potentially dysregulated miRNAs for PTE. Furthermore, the targets and involvement of each putative miRNA in different pathways were identified and evaluated. Additionally, clusters of predicted miRNAs were analyzed. Each miRNA's regulatory role was linked with apoptosis, inflammation, and cell cycle regulation pathways. Hence, these findings provide insight for future diagnostic biomarkers.
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Affiliation(s)
- Prince Kumar
- Department of Central Sophisticated Instrumentation Cell, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
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26
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Park EJ, Shimaoka M. Integrin-Mediated Exosomal Homing to Organs. Methods Mol Biol 2023; 2668:145-158. [PMID: 37140796 DOI: 10.1007/978-1-0716-3203-1_12] [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: 05/05/2023]
Abstract
Exosomes, the small extracellular vesicles of 40-150 nm in size, are secreted by nearly all types of cells and play a dynamic role in intercellular and interorgan communications. These vesicles secreted by source cells contain a variety of biologically active materials such as microRNAs (miRNAs) or proteins, thereby utilizing these cargoes in modifying molecular functionalities of the target cells in the remote tissues. Consequently, several key functions of microenvironmental niches in the tissues are regulated in an exosome-dependent manner. The precise mechanisms by which the exosomes bind and home to different organs remained largely unknown. In recent years, integrins, a large family of cell adhesion molecules, have been revealed to play a crucial role in guiding homing of exosomes to target tissues, as integrins regulate tissue-specific homing of cells. In this regard, it is imperative to experimentally determine the roles played by integrins on the exosomes in their tissue-specific homing. This chapter presents a protocol to investigate exosomal homing regulated by integrins in in vitro and in vivo settings. We focus on β7 integrin, as its role in mediating the gut-specific homing of lymphocytes has been well established.
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Affiliation(s)
- Eun Jeong Park
- Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
| | - Motomu Shimaoka
- Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
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27
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Lai C, Liao B, Peng S, Fang P, Bao N, Zhang L. Synovial fibroblast-miR-214-3p-derived exosomes inhibit inflammation and degeneration of cartilage tissues of osteoarthritis rats. Mol Cell Biochem 2023; 478:637-649. [PMID: 36001206 PMCID: PMC9938056 DOI: 10.1007/s11010-022-04535-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/30/2022] [Indexed: 11/26/2022]
Abstract
MicroRNAs (miRs) are regulators of number of cellular process. miRs enclosed within exosomes can be crucial regulators of intercellular signalling and could be an important biomarker of various age-associated disorders. Role of exosomal enclosed miRs in osteoarthritis (OA) chondrocytes and synovial fibroblasts (SFBs) remains poorly studied. Here, we profiled and studied the effect of synovial fluid-derived exosomal miRs on inflammation, survival, proliferation of chondrocyte in correlation with cartilage degeneration. Exosomes were isolated from synovial fluid collected from OA subjects and were analysed by transmission electron microscopy. miRs were isolated and were submitted to microarray profiling. Web-based PCR analysis was done. Chondrocyte proliferation and colony formation assay were performed. Apoptosis study was done by flow cytometer. Gene expression was done by qRT-PCR analysis and protein expression by western blot assay. Rat model of OA was created by operating the knee by anterior cruciate ligament and resection of medial menisci (ACLT + MMx) method. Micro-CT analysis, histological analysis, immunohistochemical staining, and TUNEL assay were also performed. About 17 miRs were found to be expressed differentially in the synovial fluid collected from the control and OA subjects. Microarray analysis confirmed, expression of miR-214-3p was significantly downregulated in the synovial fluid exosome of OA subjects. miR-214-3p mimic promoted proliferation of chondrocyte and suppressed apoptosis. Treatment also inhibited the levels of TNF-α, IL-1β and IL-6. SFB-miR-214-3p exosomes suppressed apoptosis and also inflammation in chondrocytes. In vivo study suggested that SFB-exosomal miR-214-3p from rats suppressed the formation of osteophytes, prevented degeneration of cartilage and exerted anti-inflammatory and anti-apoptotic effect in articular cartilage tissue. The findings suggested that SFB-miR-214-3p exosomes can ameliorate chondrocyte inflammation and degeneration of cartilage tissues. The study confirms therapeutic potential of SFB-miR-214-3p exosomes in treating OA.
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Affiliation(s)
- Chenteng Lai
- Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, No. 305 East Zhongshan Road, Nanjing, 210002 China
| | - Boyi Liao
- Department of Orthopedics, The People’s Hospital of Wugang City, Wugang, 422400 China
| | - Song Peng
- Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, No. 305 East Zhongshan Road, Nanjing, 210002 China
| | - Peng Fang
- Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, No. 305 East Zhongshan Road, Nanjing, 210002 China
| | - Nirong Bao
- Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, No. 305 East Zhongshan Road, Nanjing, 210002 China
| | - Lei Zhang
- Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, No. 305 East Zhongshan Road, Nanjing, 210002 China
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28
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Effect of positive pressure ventilation and bariatric surgery on extracellular vesicle microRNAs in patients with severe obesity and obstructive sleep apnea. Int J Obes (Lond) 2023; 47:24-32. [PMID: 36284205 DOI: 10.1038/s41366-022-01230-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 10/11/2022] [Accepted: 10/12/2022] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Obstructive sleep apnea (OSA) and severe obesity share a common pathophysiological phenomenon, systemic and tissue hypoxia. Hypoxaemia modifies microRNA expression, particularly, extracellular vesicles microRNAs which are involved in the progression of cardiovascular diseases, metabolic syndrome and cancer. We aim to evaluate extracellular vesicle miRNAs among patients with severe obesity with and without OSA and the effect of OSA and severe obesity treatment: continuous positive airway pressure (CPAP) and bariatric surgery. METHODS Patients were selected from the Epigenetics Modification in Morbid Obesity and Obstructive Sleep Apnea (EPIMOOSA) study (NCT03995836), a prospective observational study of patients undergoing bariatric surgery. Patients were divided into OSA (Apnea-hyponea index (AHI) > 10) and non-OSA (AHI < 10). Patients with OSA were treated with CPAP for 6 months. Then, all patients had bariatric surgery and re-evaluated 12 months later. At each visit, blood samples were obtained for biobanking. Subsequently, extracellular vesicles were extracted, and then, miRNA expression was analysed. RESULTS 15 patients with OSA and 9 without OSA completed the protocol. At baseline, patients with OSA showed higher miR16, miR126 and miR320 (p < 0.05) and lower miR223 expression (p < 0.05) than those without OSA. In patients with severe obesity and OSA, after 6 months with CPAP, we observed a significant decrease in miR21 (p < 0.01), miR126 (p < 0.001) and miR320 (p < 0.001), with no changes in any miRNA in patients without OSA. No changes were detected in any miRNA after 6 months of bariatric surgery in patients with or without OSA. CONCLUSION Co-existance of OSA and severe obesity alters the profile of extracellular vesicle miRNAs. Bariatric surgery and weight loss did not reverse this effect meanwhile the treatment with CPAP in patients with severe obesity and OSA showed a recovery outcome in those extracellular vesicle miRNAs. Those facts remark the need for OSA screening in patients with severe obesity. CLINICAL TRIAL REGISTRATION The study has also been registered at ClinicalTrials.gov identifier: NCT03995836.
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Aggio-Bruce R, Schumann U, Cioanca AV, Chen FK, McLenachan S, Heath Jeffery RC, Das S, Natoli R. Serum miRNA modulations indicate changes in retinal morphology. Front Mol Neurosci 2023; 16:1130249. [PMID: 36937046 PMCID: PMC10020626 DOI: 10.3389/fnmol.2023.1130249] [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: 12/23/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
Background Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression. Methods Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated. Results Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients. Conclusion In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.
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Affiliation(s)
- Riemke Aggio-Bruce
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
- The School of Medicine and Psychology, Acton, ACT, Australia
| | - Ulrike Schumann
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
- The Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Adrian V. Cioanca
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
| | - Fred K. Chen
- Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia
- Lions Eye Institute, Perth, WA, Australia
- Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia
| | - Samuel McLenachan
- Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia
- Lions Eye Institute, Perth, WA, Australia
| | - Rachael C. Heath Jeffery
- Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia
- Lions Eye Institute, Perth, WA, Australia
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia
| | - Shannon Das
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
| | - Riccardo Natoli
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
- The School of Medicine and Psychology, Acton, ACT, Australia
- *Correspondence: Riccardo Natoli,
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30
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Totoń-Żurańska J, Sulicka-Grodzicka J, Seweryn MT, Pitera E, Kapusta P, Konieczny P, Drabik L, Kołton-Wróż M, Chyrchel B, Nowak E, Surdacki A, Grodzicki T, Wołkow PP. MicroRNA composition of plasma extracellular vesicles: a harbinger of late cardiotoxicity of doxorubicin. Mol Med 2022; 28:156. [PMID: 36517751 PMCID: PMC9753431 DOI: 10.1186/s10020-022-00588-0] [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: 01/10/2022] [Accepted: 11/09/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The use of doxorubicin is associated with an increased risk of acute and long-term cardiomyopathy. Despite the constantly growing number of cancer survivors, little is known about the transcriptional mechanisms which progress in the time leading to a severe cardiac outcome. It is also unclear whether long-term transcriptomic alterations related to doxorubicin use are similar to transcriptomic patterns present in patients suffering from other cardiomyopathies. METHODS We have sequenced miRNA from total plasma and extracellular vesicles (EVs) from 66 acute lymphoblastic leukemia (ALL) survivors and 61 healthy controls (254 samples in total). We then analyzed processes regulated by differentially expressed circulating miRNAs and cross-validated results with the data of patients with clinically manifested cardiomyopathies. RESULTS We found that especially miRNAs contained within EVs may be informative in terms of cardiomyopathy development and may regulate pathways related to neurotrophin signaling, transforming growth factor beta (TGFβ) or epidermal growth factor receptors (ErbB). We identified vesicular miR-144-3p and miR-423-3p as the most variable between groups and significantly correlated with echocardiographic parameters and, respectively, for plasma: let-7g-5p and miR-16-2-3p. Moreover, vesicular miR-144-3p correlates with the highest number of echocardiographic parameters and is differentially expressed in the circulation of patients with dilated cardiomyopathy. We also found that distribution of particular miRNAs between of plasma and EVs (proportion between compartments) e.g., miR-184 in ALL, is altered, suggesting changes within secretory and miRNA sorting mechanisms. CONCLUSIONS Our results show that transcriptomic changes resulting from doxorubicin induced myocardial injury are reflected in circulating miRNA levels and precede development of the late onset cardiomyopathy phenotype. Among miRNAs related to cardiac function, we found vesicular miR-144-3p and miR-423-3p, as well as let-7g-5p and miR-16-2-3p contained in the total plasma. Selection of source for such studies (plasma or EVs) is of critical importance, as distribution of some miRNA between plasma and EVs is altered in ALL survivors, in comparison to healthy people, which suggests that doxorubicin-induced changes include miRNA sorting and export to extracellular space.
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Affiliation(s)
- Justyna Totoń-Żurańska
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland
| | - Joanna Sulicka-Grodzicka
- grid.5522.00000 0001 2162 9631Department of Rheumatology, Jagiellonian University Medical College, Krakow, Poland
| | - Michał T. Seweryn
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland ,grid.261331.40000 0001 2285 7943Department of Cancer Biology and Genetics, Center for Pharmacogenomics, College of Medicine, The Ohio State University, Columbus, OH USA
| | - Ewelina Pitera
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland
| | - Przemysław Kapusta
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland
| | - Paweł Konieczny
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland
| | - Leszek Drabik
- grid.5522.00000 0001 2162 9631Medical College and John Paul II Hospital, Jagiellonian University, Krakow, Poland ,grid.5522.00000 0001 2162 9631Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland
| | - Maria Kołton-Wróż
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland
| | - Bernadeta Chyrchel
- grid.5522.00000 0001 2162 9631Second Department of Cardiology, Jagiellonian University Medical College, Krakow, Poland
| | - Ewelina Nowak
- grid.5522.00000 0001 2162 9631Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland
| | - Andrzej Surdacki
- grid.5522.00000 0001 2162 9631Second Department of Cardiology, Jagiellonian University Medical College, Krakow, Poland
| | - Tomasz Grodzicki
- grid.5522.00000 0001 2162 9631Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Krakow, Poland
| | - Paweł P. Wołkow
- grid.5522.00000 0001 2162 9631Center for Medical Genomics OMICRON, Jagiellonian University Medical College, ul. Kopernika 7C, 31-034 Krakow, Poland ,grid.5522.00000 0001 2162 9631Department of Pharmacology, Jagiellonian University Medical College, Krakow, Poland
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Khashayar P, Al-Madhagi S, Azimzadeh M, Scognamiglio V, Arduini F. New frontiers in microfluidics devices for miRNA analysis. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116706] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Pradhan A, Shivaprasad S, Dey S, Goel A, Aggarwal R, Das S. Exosome-associated microRNA-375 induces cell proliferation by regulating IGFBP4 upon hepatitis C virus infection. Mol Microbiol 2022; 118:570-587. [PMID: 36203260 DOI: 10.1111/mmi.14986] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/24/2022] [Accepted: 09/26/2022] [Indexed: 11/28/2022]
Abstract
Hepatitis C virus (HCV) infection is one of the most common causes of liver cancer. HCV infection causes chronic disease followed by cirrhosis, which often leads to hepatocellular carcinoma (HCC). In this study, we investigated the roles of exosome-associated miRNAs in HCV-induced disease pathology. Small RNA sequencing was performed to identify miRNAs that are differentially regulated in exosomes isolated from patient sera at two different stages of HCV infection: cirrhosis and hepatocellular carcinoma. Among the differentially expressed miRNAs, miR-375 was found to be significantly upregulated in exosomes isolated from patients with cirrhosis and HCC. A similar upregulation was observed in intracellular and extracellular/exosomal levels of miR-375 in HCV-JFH1 infected Huh7.5 cells. The depletion of miR-375 in infected cells inhibited HCV-induced cell migration and proliferation, suggesting a supportive role for miR-375 in HCV pathogenesis. miR-375, secreted through exosomes derived from HCV-infected cells, could also be transferred to naïve Huh7.5 cells, resulting in an increase in cell proliferation and migration in the recipient cells. Furthermore, we identified Insulin growth factor binding protein 4 (IGFBP4), a gene involved in cell growth and malignancy, as a novel target of miR-375. Our results demonstrate the critical involvement of exosome-associated miR-375 in HCV-induced disease progression.
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Affiliation(s)
- Aunji Pradhan
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
| | - Shwetha Shivaprasad
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
| | - Shuchismita Dey
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
| | - Amit Goel
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Saumitra Das
- Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India
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Xu D, Di K, Fan B, Wu J, Gu X, Sun Y, Khan A, Li P, Li Z. MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology. Front Bioeng Biotechnol 2022; 10:948959. [PMID: 36324901 PMCID: PMC9618890 DOI: 10.3389/fbioe.2022.948959] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 09/30/2022] [Indexed: 11/13/2022] Open
Abstract
MicroRNAs (miRNAs) are a class of short, single-stranded, noncoding RNAs, with a length of about 18–22 nucleotides. Extracellular vesicles (EVs) are derived from cells and play a vital role in the development of diseases and can be used as biomarkers for liquid biopsy, as they are the carriers of miRNA. Existing studies have found that most of the functions of miRNA are mainly realized through intercellular transmission of EVs, which can protect and sort miRNAs. Meanwhile, detection sensitivity and specificity of EV-derived miRNA are higher than those of conventional serum biomarkers. In recent years, EVs have been expected to become a new marker for liquid biopsy. This review summarizes recent progress in several aspects of EVs, including sorting mechanisms, diagnostic value, and technology for isolation of EVs and detection of EV-derived miRNAs. In addition, the study reviews challenges and future research avenues in the field of EVs, providing a basis for the application of EV-derived miRNAs as a disease marker to be used in clinical diagnosis and even for the development of point-of-care testing (POCT) platforms.
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Affiliation(s)
- Dongjie Xu
- College of Animal Science, Yangtze University, Jingzhou, China
| | - Kaili Di
- Department of Laboratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Boyue Fan
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Jie Wu
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Xinrui Gu
- Department of Laboratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Yifan Sun
- Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China
| | - Adeel Khan
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, National Demonstration Center for Experimental Biomedical Engineering Education (Southeast University), Southeast University, Nanjing, China
| | - Peng Li
- College of Animal Science, Yangtze University, Jingzhou, China
- *Correspondence: Peng Li, ; Zhiyang Li,
| | - Zhiyang Li
- Department of Laboratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
- *Correspondence: Peng Li, ; Zhiyang Li,
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Differentially Expressed microRNAs in Peritoneal Dialysis Effluent-Derived Exosomes from the Patients with Ultrafiltration Failure. Genet Res (Camb) 2022; 2022:2276175. [PMID: 36101746 PMCID: PMC9452989 DOI: 10.1155/2022/2276175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 08/01/2022] [Accepted: 08/12/2022] [Indexed: 11/20/2022] Open
Abstract
Background Ultrafiltration failure remains one of the most severe complications of long-term peritoneal dialysis (PD), which results in death. This study aimed to characterize the circulating exosomal microRNA (miRNA) profiles associated with ultrafiltration failure and explore its underlying mechanisms. Methods Exosomes were isolated from the peritoneal dialysis effluent (PDE) of patients with ultrafiltration failure or success using the ultracentrifugation method, and then transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot were used for exosome characterization. After that, the isolated exosomes were sent for small RNA sequencing, and eight differentially expressed miRNAs (DE-miRNAs) were chosen for RT-qPCR validation. Results TEM, NTA, and western blot revealed that exosomes were successfully isolated. After sequencing, 70 DE-miRNAs involved in ultrafiltration were identified, including 41 upregulated ones and 29 downregulated ones. Functional analyses revealed that these DE-miRNAs were significantly enriched in pathways of cancer, ubiquitin-mediated proteolysis, axon orientation, and the Rap1 and Ras signaling pathways. In addition, the consistency rate of RT-qPCR and sequencing results was 75%, which indicated the relatively high reliability of the sequencing data. Conclusions Our findings implied that these DE-miRNAs may be potential biomarkers of ultrafiltration failure, which would help us to discover novel therapeutic targets/pathways for ultrafiltration failure in patients with end-stage renal disease.
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Ghoreishi E, Shahrokhi SZ, Kazerouni F, Rahimipour A. Circulating miR-148b-3p and miR-27a-3p can be potential biomarkers for diagnosis of pre-diabetes and type 2 diabetes: integrating experimental and in-silico approaches. BMC Endocr Disord 2022; 22:207. [PMID: 35978298 PMCID: PMC9386953 DOI: 10.1186/s12902-022-01120-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 08/02/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND In view of the growing global prevalence of type 2 diabetes (T2D), detection of prediabetes and type 2 diabetes in the early stages is necessary to reduce the risk of developing diabetes, prevent the progression of the disease, and dysfunction of different organs. Since miRNAs are involved in the initiation and progression of numerous pathogenic processes, including diabetes, in the present study, we aimed to investigate the expression of miR-148b-3p and miR-27a-3p in prediabetic and T2D patients and to evaluate the diagnostic potential of these miRNAs. METHODS We evaluated the expression of miR-148b-3p and miR-27a-3p in the plasma of three groups: 20 prediabetic patients, 20 T2D patients, and 20 healthy controls. The biochemical parameters were determined by the auto-analyzer. The possible target genes of these miRNAs were identified using an in-silico approach. RESULTS Our results showed that, as compared to the healthy controls, there was a significant up regulation and down regulation in the expression of miR-148b-3p and miR-27a-3p in the T2D patients, respectively. The results of receiver operating characteristic curve analysis also suggested that miR-148b-3p acted successfully in discriminating the prediabetic and diabetic patients from the control group. According to in-silico analysis, miRs influence biological pathways involved in T2DM development, such as insulin signaling. CONCLUSIONS The miR148b-3p and miR-27a-3p expression levels were deregulated in diabetes and pre-diabetes. Furthermore, miR-148b-3p showed significant ability in discriminating between diabetic and healthy individuals, suggesting a potential diagnostic use of miR-148b-3p in the detection of T2D.
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Affiliation(s)
- Elnaz Ghoreishi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyedeh Zahra Shahrokhi
- Department of Biochemistry, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Faranak Kazerouni
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ali Rahimipour
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Xiang K, Akram M, Elbossaty WF, Yang J, Fan C. Exosomes in atrial fibrillation: therapeutic potential and role as clinical biomarkers. Heart Fail Rev 2022; 27:1211-1221. [PMID: 34251579 DOI: 10.1007/s10741-021-10142-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/05/2021] [Indexed: 12/21/2022]
Abstract
Atrial fibrillation (AF), the most common cardiac arrhythmia, is a global epidemic. AF can cause heart failure and myocardial infarction and increase the risk of stroke, disability, and thromboembolic events. AF is becoming increasingly ubiquitous and is associated with increased morbidity and mortality at higher ages, resulting in an increasing threat to human health as well as substantial medical and social costs. Currently, treatment strategies for AF focus on controlling heart rate and rhythm with medications to restore and maintain sinus rhythm, but this approach has limitations. Catheter ablation is not entirely satisfactory and does not address the issues underlying AF. Research exploring the mechanisms causing AF is urgently needed for improved prevention, diagnosis, and treatment of AF. Exosomes are small vesicles (30-150 nm) released by cells that transmit information between cells. MicroRNAs in exosomes play an important role in the pathogenesis of AF and are established as a biomarker for AF. In this review, a summary of the role of exosomes in AF is presented. The role of exosomes and microRNAs in AF occurrence, their therapeutic potential, and their potential role as clinical biomarkers is considered. A better understanding of exosomes has the potential to improve the prognosis of AF patients worldwide, reducing the global medical burden of this disease.
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Affiliation(s)
- Kun Xiang
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China
| | - Muhammad Akram
- Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan
| | | | - Jinfu Yang
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China
| | - Chengming Fan
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China.
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Walsh SA, Davis TA. Key early proinflammatory signaling molecules encapsulated within circulating exosomes following traumatic injury. J Inflamm (Lond) 2022; 19:6. [PMID: 35551611 PMCID: PMC9097360 DOI: 10.1186/s12950-022-00303-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 03/26/2022] [Indexed: 12/28/2022] Open
Abstract
Background Assessment of immune status in critically ill patients is often based on serial tracking of systemic cytokine levels and clinical laboratory values. Exosomes are extracellular vesicles that can be secreted and internalized by cells to transport important cellular cargo in the regulation of numerous physiological and pathological processes. Here, we characterize the early compartmentalization profile of key proinflammatory mediators in serum exosomes in the steady state and following trauma. Adult male Sprague-Dawley rats (91 including naïve) were divided into one of four traumatic injury model groups incorporating whole-body blast, fracture, soft-tissue crush injury, tourniquet-induced ischemia, and limb amputation. Serum was collected at 1, 3, 6, and 24 h, and 3- and 7-day post-injury. Electrochemiluminescence-based immunoassays for 9 key proinflammatory mediators in whole serum, isolated serum exosomes, and exosome depleted serum were analyzed and compared between naïve and injured rats. Serum clinical chemistry analysis was performed to determine pathological changes. Results In naïve animals, substantial amounts of IL-1β, IL-10, and TNF-α were encapsulated, IL-6 was completely encapsulated, and CXCL1 freely circulating. One hour after blast injury alone, levels of exosome encapsulated IFN-γ, IL-10, IL-6, IL-13, IL-4, and TNF-α increased, whereas freely circulating and membrane-associated levels remained undetectable or low. Rats with the most severe polytraumatic injuries with end organ complications had the earliest rise and most pronounced concentration of IL-1β, IL-10, TNF-α, and IL-6 across all serum compartments. Moreover, CXCL1 levels increased in relation to injury severity, but remained almost entirely freely circulating at all timepoints. Conclusion These findings highlight that conventional ELISA-based assessments, which detect only free circulating and exosome membrane-bound mediators, underestimate the full immunoinflammatory response to trauma. Inclusion of exosome encapsulated mediators may be a better, more accurate and clinically useful early strategy to identify, diagnose, and monitor patients at highest risk for post-traumatic inflammation-associated complications.
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Affiliation(s)
- Sarah A Walsh
- Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA
| | - Thomas A Davis
- Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
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Sanghani A, Andriesei P, Kafetzis KN, Tagalakis AD, Yu‐Wai‐Man C. Advances in exosome therapies in ophthalmology-From bench to clinical trial. Acta Ophthalmol 2022; 100:243-252. [PMID: 34114746 DOI: 10.1111/aos.14932] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Accepted: 05/20/2021] [Indexed: 12/15/2022]
Abstract
During the last decade, the fields of advanced and personalized therapeutics have been constantly evolving, utilizing novel techniques such as gene editing and RNA therapeutic approaches. However, the method of delivery and tissue specificity remain the main hurdles of these approaches. Exosomes are natural carriers of functional small RNAs and proteins, representing an area of increasing interest in the field of drug delivery. It has been demonstrated that the exosome cargo, especially miRNAs, is at least partially responsible for the therapeutic effects of exosomes. Exosomes deliver their luminal content to the recipient cells and can be used as vesicles for the therapeutic delivery of RNAs and proteins. Synthetic therapeutic drugs can also be encapsulated into exosomes as they have a hydrophilic core, which makes them suitable to carry water-soluble drugs. In addition, engineered exosomes can display a variety of surface molecules, such as peptides, to target specific cells in tissues. The exosome properties present an added advantage to the targeted delivery of therapeutics, leading to increased efficacy and minimizing the adverse side effects. Furthermore, exosomes are natural nanoparticles found in all cell types and as a result, they do not elicit an immune response when administered. Exosomes have also demonstrated decreased long-term accumulation in tissues and organs and thus carry a low risk of systemic toxicity. This review aims to discuss all the advances in exosome therapies in ophthalmology and to give insight into the challenges that would need to be overcome before exosome therapies can be translated into clinical practice.
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Affiliation(s)
- Amisha Sanghani
- Faculty of Life Sciences & Medicine King’s College London London UK
- Department of Ophthalmology St Thomas’ Hospital London UK
| | - Petru Andriesei
- Faculty of Life Sciences & Medicine King’s College London London UK
- Department of Ophthalmology St Thomas’ Hospital London UK
| | | | | | - Cynthia Yu‐Wai‐Man
- Faculty of Life Sciences & Medicine King’s College London London UK
- Department of Ophthalmology St Thomas’ Hospital London UK
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Compagnoni C, Zelli V, Bianchi A, Di Marco A, Capelli R, Vecchiotti D, Brandolini L, Cimini AM, Zazzeroni F, Allegretti M, Alesse E, Tessitore A. MicroRNAs Expression in Response to rhNGF in Epithelial Corneal Cells: Focus on Neurotrophin Signaling Pathway. Int J Mol Sci 2022; 23:ijms23073597. [PMID: 35408969 PMCID: PMC8998691 DOI: 10.3390/ijms23073597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 11/16/2022] Open
Abstract
PURPOSE Nerve growth factor efficacy was demonstrated for corneal lesions treatment, and recombinant human NGF (rhNGF) was approved for neurotrophic keratitis therapy. However, NGF-induced molecular responses in cornea are still largely unknown. We analyzed microRNAs expression in human epithelial corneal cells after time-dependent rhNGF treatment. METHODS Nearly 700 microRNAs were analyzed by qRT-PCR. MicroRNAs showing significant expression differences were examined by DIANA-miRpath v.3.0 to identify target genes and pathways. Immunoblots were performed to preliminarily assess the strength of the in silico results. RESULTS Twenty-one microRNAs (miR-26a-1-3p, miR-30d-3p, miR-27b-5p, miR-146a-5p, miR-362-5p, mir-550a-5p, mir-34a-3p, mir-1227-3p, mir-27a-5p, mir-222-5p, mir-151a-5p, miR-449a, let7c-5p, miR-337-5p, mir-29b-3p, miR-200b-3p, miR-141-3p, miR-671-3p, miR-324-5p, mir-411-3p, and mir-425-3p) were significantly regulated in response to rhNGF. In silico analysis evidenced interesting target genes and pathways, including that of neurotrophin, when analyzed in depth. Almost 80 unique target genes (e.g., PI3K, AKT, MAPK, KRAS, BRAF, RhoA, Cdc42, Rac1, Bax, Bcl2, FasL) were identified as being among those most involved in neurotrophin signaling and in controlling cell proliferation, growth, and apoptosis. AKT and RhoA immunoblots demonstrated congruence with microRNA expression, providing preliminary validation of in silico data. CONCLUSIONS MicroRNA levels in response to rhNGF were for the first time analyzed in corneal cells. Novel insights about microRNAs, target genes, pathways modulation, and possible biological responses were provided. Importantly, given the putative role of microRNAs as biomarkers or therapeutic targets, our results make available data which might be potentially exploitable for clinical applications.
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Affiliation(s)
- Chiara Compagnoni
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
| | - Veronica Zelli
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
- Center for Molecular Diagnostics and Advanced Therapies, University of L’Aquila, Via Petrini, 67100 L’Aquila, Italy
| | - Andrea Bianchi
- Department of Information Engineering, Computer Science and Mathematics, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (A.B.); (A.D.M.)
| | - Antinisca Di Marco
- Department of Information Engineering, Computer Science and Mathematics, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (A.B.); (A.D.M.)
| | - Roberta Capelli
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
| | - Davide Vecchiotti
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
- Center for Molecular Diagnostics and Advanced Therapies, University of L’Aquila, Via Petrini, 67100 L’Aquila, Italy
| | - Laura Brandolini
- Dompé Farmaceutici Spa, via Campo di Pile, 1, 67100 L’Aquila, Italy; (L.B.); (M.A.)
| | - Anna Maria Cimini
- Department of Life, Health and Environmental Sciences, University of L’Aquila, P.zza S. Tommasi, 67100 L’Aquila, Italy;
| | - Francesca Zazzeroni
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
| | - Marcello Allegretti
- Dompé Farmaceutici Spa, via Campo di Pile, 1, 67100 L’Aquila, Italy; (L.B.); (M.A.)
| | - Edoardo Alesse
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
| | - Alessandra Tessitore
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (C.C.); (V.Z.); (R.C.); (D.V.); (F.Z.); (E.A.)
- Center for Molecular Diagnostics and Advanced Therapies, University of L’Aquila, Via Petrini, 67100 L’Aquila, Italy
- Correspondence: ; Tel.: +39-086-243-3518; Fax: +39-0862433131
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Luo F, Liu W, Bu H. MicroRNAs in hypertrophic cardiomyopathy: pathogenesis, diagnosis, treatment potential and roles as clinical biomarkers. Heart Fail Rev 2022; 27:2211-2221. [PMID: 35332416 DOI: 10.1007/s10741-022-10231-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2022] [Indexed: 12/28/2022]
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is characterized by increased left ventricular wall thickness, but existing diagnostic and treatment approaches face limitations. MicroRNAs (miRNAs) are type of noncoding RNA molecule that plays crucial roles in the pathological process of cardiac remodelling. Accordingly, miRNAs related to HCM may represent potential novel therapeutic targets. In this review, we first discuss the different roles of miRNAs in the development of HCM. We then summarize the roles of common miRNAs as diagnostic and clinical biomarkers in HCM. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HCM.
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Affiliation(s)
- Fanyan Luo
- The Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.,National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Wei Liu
- The Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China.,National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Haisong Bu
- The Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People's Republic of China. .,National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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Preethi KA, Selvakumar SC, Ross K, Jayaraman S, Tusubira D, Sekar D. Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer. Mol Cancer 2022; 21:54. [PMID: 35172817 PMCID: PMC8848669 DOI: 10.1186/s12943-022-01525-9] [Citation(s) in RCA: 112] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/26/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.
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Affiliation(s)
- K. Auxzilia Preethi
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu 600077 India
| | - Sushmaa Chandralekha Selvakumar
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu 600077 India
| | - Kehinde Ross
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
| | - Selvaraj Jayaraman
- Department of Biochemistry, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, 600077 India
| | - Deusdedit Tusubira
- Biochemistry Department, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Durairaj Sekar
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu 600077 India
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Mahmoudi A, Butler AE, Jamialahmadi T, Sahebkar A. The role of exosomal miRNA in nonalcoholic fatty liver disease. J Cell Physiol 2022; 237:2078-2094. [PMID: 35137416 DOI: 10.1002/jcp.30699] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/21/2022] [Accepted: 01/25/2022] [Indexed: 12/14/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) impacts more than one-third of the population and is linked with other metabolic diseases. The term encompasses a wide spectrum of diseases, from modest steatosis to nonalcoholic steatohepatitis, fibrosis and, ultimately, cirrhosis with the potential for development of hepatocellular carcinoma. Currently, available methods for diagnosing NAFLD are invasive or lack accuracy, and monitoring to determine response to therapeutic interventions is challenging. Exosomes are nano-scaled extracellular vesicles that are secreted by a variety of cells. They convey proteins, mRNA, miRNA, and other bioactive molecules between cells and are involved in an extensive range of biological processes, particularly cell-cell communication. Several reports suggest that exosomes mediate miRNAs and, thus, they have potential clinical utility for diagnosis, prognosis, and therapeutics in liver diseases. In view of the vital role of exosomal microRNA in disease, we here synthesized current knowledge about the biogenesis of exosomal miRNA and exosome-mediated microRNA transfer. We then discuss the potential of exosomal miRNA in diagnosis and therapeutics of NAFLD.
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Affiliation(s)
- Ali Mahmoudi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Tannaz Jamialahmadi
- Surgical Oncology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Medicine, The University of Western Australia, Perth, Australia.,Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Bencun M, Britto-Borges T, Eschenbach J, Dieterich C. New Tricks with Old Dogs: Computational Identification and Experimental Validation of New miRNA–mRNA Regulation in hiPSC-CMs. Biomedicines 2022; 10:biomedicines10020391. [PMID: 35203600 PMCID: PMC8962266 DOI: 10.3390/biomedicines10020391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/27/2022] [Accepted: 02/03/2022] [Indexed: 02/04/2023] Open
Abstract
Cardiovascular disease is still the leading cause of morbidity and mortality worldwide. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a valuable widespread in vitro model to study cardiac disease. Herein, we employ the hiPSC-CM model to identify novel miRNA–mRNA interaction partners during cardiac differentiation and β-adrenergic stress. Whole transcriptome and small RNA sequencing data were combined to identify novel miRNA–mRNA interactions. Briefly, mRNA and miRNA expression profiles were integrated with miRNA target predictions to identify significant statistical dependencies between a miRNA and its candidate target set. We show by experimental validation that our approach discriminates true from false miRNA target predictions. Thereby, we identified several differentially expressed miRNAs and focused on the two top candidates: miR-99a-5p in the context of cardiac differentiation and miR-212-3p in the context of β-adrenergic stress. We validated some target mRNA candidates by 3′UTR luciferase assays as well as in transfection experiments in the hiPSC-CM model system. Our data show that iPSC-derived cardiomyocytes and computational modeling can be used to uncover new valid miRNA–mRNA interactions beyond current knowledge.
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Affiliation(s)
- Maja Bencun
- Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany; (M.B.); (T.B.-B.); (J.E.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Thiago Britto-Borges
- Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany; (M.B.); (T.B.-B.); (J.E.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Jessica Eschenbach
- Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany; (M.B.); (T.B.-B.); (J.E.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Christoph Dieterich
- Section of Bioinformatics and Systems Cardiology, Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany; (M.B.); (T.B.-B.); (J.E.)
- DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany
- Department of Internal Medicine III (Cardiology, Angiology, and Pneumology), University Hospital Heidelberg, 69120 Heidelberg, Germany
- Correspondence: ; Tel.: +49-6221-56-36884
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Pawlica P, Yario TA, White S, Wang J, Moss WN, Hui P, Vinetz JM, Steitz JA. SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes. Proc Natl Acad Sci U S A 2021; 118:e2116668118. [PMID: 34903581 PMCID: PMC8719879 DOI: 10.1073/pnas.2116668118] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/28/2021] [Indexed: 12/13/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern. In this study, we investigated the impact of SARS-CoV-2 infection on host microRNA (miRNA) populations in three human lung-derived cell lines, as well as in nasopharyngeal swabs from SARS-CoV-2-infected individuals. We did not detect any major and consistent differences in host miRNA levels after SARS-CoV-2 infection. However, we unexpectedly discovered a viral miRNA-like small RNA, named CoV2-miR-O7a (for SARS-CoV-2 miRNA-like ORF7a-derived small RNA). Its abundance ranges from low to moderate as compared to host miRNAs and it associates with Argonaute proteins-core components of the RNA interference pathway. We identify putative targets for CoV2-miR-O7a, including Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF2), which participates in interferon signaling. We demonstrate that CoV2-miR-O7a production relies on cellular machinery, yet is independent of Drosha protein, and is enhanced by the presence of a strong and evolutionarily conserved hairpin formed within the ORF7a sequence.
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Affiliation(s)
- Paulina Pawlica
- Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536;
| | - Therese A Yario
- Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536
- HHMI, Yale University School of Medicine, New Haven, CT 06536
| | - Sylvia White
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06536
| | - Jianhui Wang
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06536
| | - Walter N Moss
- Roy J. Carver Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011
| | - Pei Hui
- Department of Pathology, Yale University School of Medicine, New Haven, CT 06536
| | - Joseph M Vinetz
- Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520
| | - Joan A Steitz
- Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536;
- HHMI, Yale University School of Medicine, New Haven, CT 06536
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Flemming JP, Hill BL, Anderson-Pullinger L, Harshyne LA, Mahoney MG. Cytokine Profiling in Low- and High-Density Small Extracellular Vesicles from Epidermoid Carcinoma Cells. JID INNOVATIONS 2021; 1:100053. [PMID: 34909749 PMCID: PMC8659799 DOI: 10.1016/j.xjidi.2021.100053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/21/2021] [Accepted: 07/23/2021] [Indexed: 01/08/2023] Open
Abstract
Exosomes or small extracellular vesicles (sEVs) are membrane-bound nanoparticles that carry various macromolecules and act as autocrine and paracrine signaling messengers. In this study, sEVs from epidermoid carcinoma cells influenced by membrane presentation of the glycoprotein desmoglein 2 and its palmitoylation state were investigated. In this study, sEVs were isolated by sequential ultracentrifugation followed by iodixanol density gradient separation. They were then subjected to multiplex profiling of cytokines associated with the surface of intact sEVs. The results revealed a previously undescribed active sorting of cytokines onto the surface of low-density and high-density sEV subpopulations. Specifically, an altered surface presentation of desmoglein 2 decreased FGF-2 and VEGF in low-density sEVs. In addition, in response to desmoglein 2, IL-8 and RANTES were increased in low-density sEVs but only slightly decreased in high-density sEVs. Finally, IL-6 and G-CSF were increased dramatically in high-density sEVs. This comprehensive analysis of the cytokine production profile by squamous cell carcinoma‒derived sEVs highlights their contribution to immune evasion, pro-oncogenic and proangiogenic activity, and the potential to identify diagnostic disease biomarkers.
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Affiliation(s)
- Joseph P. Flemming
- Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Brianna L. Hill
- Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | | | - Larry A. Harshyne
- Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Mỹ G. Mahoney
- Department of Dermatology & Cutaneous Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
- Department of Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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A simple "signal off-on" fluorescence nanoplatform for the label-free quantification of exosome-derived microRNA-21 in lung cancer plasma. Mikrochim Acta 2021; 188:397. [PMID: 34716495 DOI: 10.1007/s00604-021-05051-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 10/07/2021] [Indexed: 10/20/2022]
Abstract
A simple nanoplatform based on molybdenum disulfide (MoS2) nanosheets, a fluorescence quencher (signal off), and a hybridization chain reaction (HCR) signal amplification (signal on) used for the enzyme-free, label-free, and low-background signal quantification of microRNA-21 in plasma exosome is reported. According to the sequence of microRNA-21, carboxy-fluorescein (FAM)-labeled hybridization probe 1 (FAM-H1) and hybridization probes 2 (FAM-H2) were designed with excitation maxima at 488 nm and emission maxima at 518 nm. MoS2 nanosheets could adsorb FAM-H1 and FAM-H2 and quenched their fluorescence signals to reduce the background signal. However, HCR was triggered when microRNA-21 was present. Consequently, HCR products containing a large number of FAM fluorophores can emit a strong fluorescence at 518 nm and could realize the detection of microRNA-21 as low as 6 pmol/L and had a wide linear relation of 0.01-25 nmol/L. This assay has the ability of single-base mismatch recognition and could identify microRNA-21 with high specificity. Most importantly, this approach was successfully applied to the detection of plasma exosomal microRNA-21 in patients with lung cancer, and it is proposed that other targets can also be detected by changing the FAM-H1 and FAM-H2 corresponding to the target sequence. Thus, a novel, hands-on strategy for liquid biopsy was proposed and has a potential application value in the early diagnosis of lung cancer.
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Pertusa C, Tarín JJ, Cano A, García-Pérez MÁ, Mifsut D. Serum microRNAs in osteoporotic fracture and osteoarthritis: a genetic and functional study. Sci Rep 2021; 11:19372. [PMID: 34588560 PMCID: PMC8481273 DOI: 10.1038/s41598-021-98789-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 09/13/2021] [Indexed: 02/08/2023] Open
Abstract
The rising incidence of bone pathologies such as osteoporosis and osteoarthritis is negatively affecting the functional status of millions of patients worldwide. The genetic component of these multifactorial pathologies is far from being fully understood, but in recent years several epigenetic mechanisms involved in the pathophysiology of these bone diseases have been identified. The aim of the present study was to compare the serum expression of four miRNAs in women with hip fragility fracture (OF group), osteoarthritis requiring hip replacement (OA group) and control women (Ctrl group). Serum expression of miR-497-5p, miR-155-5p, miR-423-5p and miR-365-3p was determined in a sample of 23 OA women, 25 OF women and 52 Ctrl women. Data shown that women with bone pathologies have higher expression of miR-497 and miR-423 and lower expression of miR-155 and miR-365 than control subjects. Most importantly, miR-497 was identified as an excellent discriminator between OA group and control group (AUC: 0.89, p < 0.000) and acceptable in distinguishing from the OF group (AUC: 0.76, p = 0.002). Our data suggest that circulating miR-497 may represent a significant biomarker of OA, a promising finding that could contribute towards future early-stage diagnosis of this disease. Further studies are required to establish the role of miR-155, miR-423 and miR-365 in bone pathologies.
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Affiliation(s)
- Clara Pertusa
- grid.429003.cResearch Unit, INCLIVA Health Research Institute, 46010 Valencia, Spain
| | - Juan J. Tarín
- grid.5338.d0000 0001 2173 938XDepartment of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, 46100 Burjassot, Spain
| | - Antonio Cano
- grid.5338.d0000 0001 2173 938XDepartment of Pediatrics, Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain
| | - Miguel Ángel García-Pérez
- grid.429003.cResearch Unit, INCLIVA Health Research Institute, 46010 Valencia, Spain ,grid.5338.d0000 0001 2173 938XDepartment of Genetics, University of Valencia, 46100 Burjassot, Spain
| | - Damián Mifsut
- Orthopedic Surgery and Traumatology, Clinic Hospital, INCLIVA Institute of Health Research, 46010 Valencia, Spain
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Jin Y, Ai L, Chai X, Tang P, Zhang W, Yang L, Hu Y, Xu Y, Li S. Maternal Circulating Exosomal miRNAs as Non-invasive Biomarkers for the Prediction of Fetal Ventricular Septal Defect. Front Genet 2021; 12:717208. [PMID: 34567071 PMCID: PMC8458870 DOI: 10.3389/fgene.2021.717208] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/16/2021] [Indexed: 11/22/2022] Open
Abstract
Objective: This study aimed to identify maternal circulating exosomal miRNAs as potential non-invasive biomarkers for the early detection of fetal ventricular septal defects (VSDs). Methods: In total, 182 pregnant women, comprising 91 VSD cases and 91 matched controls, were included in this study. Exosomes were isolated; dysregulated exosomal miRNAs were profiled using next-generation sequencing. Differential abundance of miRNAs was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Diagnostic accuracy was evaluated by constructing receiver operating characteristic (ROC) curves. Results: In total, 77 serum exosomal miRNAs were found to be differentially expressed in the VSD group compared to their expression in the control group. Among these, five downregulated exosomal miRNAs were validated using qRT-PCR. hsa-miR-146a-5p was identified to be capable of distinguishing VSD cases from controls (area under the ROC curve [AUC]: 0.997; p < 1.00E-05). Conclusion: Circulating exosomal miRNAs, particularly hsa-miR-146a-5p, may be predictive biomarkers for the non-invasive prenatal diagnosis of fetal VSDs.
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Affiliation(s)
- Yuxia Jin
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Ling Ai
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Xiaojun Chai
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Ping Tang
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Weihua Zhang
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Li Yang
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Yue Hu
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
| | - Ying Xu
- College of Medicine, Jiaxing University, Jiaxing, China
| | - Suping Li
- Department of Prenatal Diagnostic, Jiaxing Maternity and Children Health Care Hospital, Jiaxing University, Jiaxing, China
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Zelli V, Compagnoni C, Capelli R, Corrente A, Cornice J, Vecchiotti D, Di Padova M, Zazzeroni F, Alesse E, Tessitore A. Emerging Role of isomiRs in Cancer: State of the Art and Recent Advances. Genes (Basel) 2021; 12:genes12091447. [PMID: 34573429 PMCID: PMC8469436 DOI: 10.3390/genes12091447] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/16/2021] [Accepted: 09/17/2021] [Indexed: 12/12/2022] Open
Abstract
The advent of Next Generation Sequencing technologies brought with it the discovery of several microRNA (miRNA) variants of heterogeneous lengths and/or sequences. Initially ascribed to sequencing errors/artifacts, these isoforms, named isomiRs, are now considered non-canonical variants that originate from physiological processes affecting the canonical miRNA biogenesis. To date, accurate IsomiRs abundance, biological activity, and functions are not completely understood; however, the study of isomiR biology is an area of great interest due to their high frequency in the human miRNome, their putative functions in cooperating with the canonical miRNAs, and potential for exhibiting novel functional roles. The discovery of isomiRs highlighted the complexity of the small RNA transcriptional landscape in several diseases, including cancer. In this field, the study of isomiRs could provide further insights into the miRNA biology and its implication in oncogenesis, possibly providing putative new cancer diagnostic, prognostic, and predictive biomarkers as well. In this review, a comprehensive overview of the state of research on isomiRs in different cancer types, including the most common tumors such as breast cancer, colorectal cancer, melanoma, and prostate cancer, as well as in the less frequent tumors, as for example brain tumors and hematological malignancies, will be summarized and discussed.
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Affiliation(s)
- Veronica Zelli
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
- Center for Molecular Diagnostics and Advanced Therapies, University of L’Aquila, Via Petrini, 67100 L’Aquila, Italy
| | - Chiara Compagnoni
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Roberta Capelli
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Alessandra Corrente
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Jessica Cornice
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Davide Vecchiotti
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Monica Di Padova
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Francesca Zazzeroni
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Edoardo Alesse
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
| | - Alessandra Tessitore
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio, 67100 L’Aquila, Italy; (V.Z.); (C.C.); (R.C.); (A.C.); (J.C.); (D.V.); (M.D.P.); (F.Z.); (E.A.)
- Center for Molecular Diagnostics and Advanced Therapies, University of L’Aquila, Via Petrini, 67100 L’Aquila, Italy
- Correspondence: ; Tel.: +39-0862433518; Fax: +39-0862433131
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Xiao PP, Wan QQ, Liao T, Tu JY, Zhang GJ, Sun ZY. Peptide Nucleic Acid-Functionalized Nanochannel Biosensor for the Highly Sensitive Detection of Tumor Exosomal MicroRNA. Anal Chem 2021; 93:10966-10973. [PMID: 34327982 DOI: 10.1021/acs.analchem.1c01898] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Compared with free miRNAs in blood, miRNAs in exosomes have higher abundance and stability. Therefore, miRNAs in exosomes can be regarded as an ideal tumor marker for early cancer diagnosis. Here, a peptide nucleic acid (PNA)-functionalized nanochannel biosensor for the ultrasensitive and specific detection of tumor exosomal miRNAs is proposed. After PNA was covalently bound to the inner surface of the nanochannels, the detection of tumor exosomal miRNAs was achieved by the charge changes on the surface of nanochannels before and after hybridization (PNA-miRNA). Due to the neutral characteristics of PNA, the efficiency of PNA-miRNA hybridization was improved by significantly reducing the background signal. This biosensor could not only specifically distinguish target miRNA-10b from single-base mismatched miRNA but also achieve a detection limit as low as 75 aM. Moreover, the biosensor was further used to detect exosomal miRNA-10b derived from pancreatic cancer cells and normal pancreatic cells. The results indicate that this biosensor could effectively distinguish pancreatic cancer tumor-derived exosomes from the normal control group, and the detection results show good consistency with those of the quantitative reverse-transcription polymerase chain reaction method. In addition, the biosensor was used to detect exosomal miRNA-10b in clinical plasma samples, and it was found that the content of exosomal miRNA-10b in cancer patients was generally higher than that of healthy individuals, proving that the method is expected to be applied for the early diagnosis of cancer.
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Affiliation(s)
- Ping-Ping Xiao
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
| | - Qiang-Qiang Wan
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
- Wuhan First Hospital, Wuhan 430022, China
| | - Tangbin Liao
- School of Pharmacy, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
| | - Ji-Yuan Tu
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
| | - Guo-Jun Zhang
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
| | - Zhong-Yue Sun
- School of Laboratory Medicine, Hubei University of Chinese Medicine, 16 Huangjia Lake West Road, Wuhan 430065, China
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