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1
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Yu S, Zhao S, Liu Y, Gu T, Wen SH, Ma J, Dang Y, Zhu JJ, Zhou Y. A telomerase-enhanced homogeneous cascade amplification strategy designed for highly sensitive electrochemical detection of microRNA. Biosens Bioelectron 2025; 279:117422. [PMID: 40158493 DOI: 10.1016/j.bios.2025.117422] [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: 01/19/2025] [Revised: 03/20/2025] [Accepted: 03/25/2025] [Indexed: 04/02/2025]
Abstract
Highly sensitive and specific detection of microRNAs (miRNAs) is vital for cancer early diagnosis. In this work, we have proposed a telomerase-enhanced homogeneous cascade amplification strategy for high-performance electrochemical detection of miRNA-21 (miR-21). The target miRNA is first transcribed and amplified into massive single-stranded output DNA fragments through the endonucleases-assisted primary amplification element. Then, the output DNAs can activate the telomerase-promoted entropy-driven DNA catalytic (EDC) circuit, which can significantly improve the amplification efficiency and release a mass of linker DNAs, achieving the secondary amplification of miR-21. Finally, the G-quadruplex loaded with plenty of electroactive substances can be captured on the electrode via the linker DNAs for highly sensitive detection of miR-21. The fabricated electrochemical biosensor exhibits a broad linear range from 1 aM to 1 nM with the detection limit of 0.36 aM. The exceptional sensitivity and specificity endow this biosensor with the ability to discriminate miR-21 from the interference miRNAs and proteins. In addition, the biosensor has been utilized to analyze miR-21 expression levels in human serum and diverse cell lysates, demonstrating its practicability in real sample analysis. Therefore, our designed electrochemical biosensor will have huge potential in analysis of cancer-related miRNA and early cancer diagnosis.
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Affiliation(s)
- Sha Yu
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China
| | - Shaodi Zhao
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China
| | - Yibo Liu
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China
| | - Tongnian Gu
- Sunresin New Materials Co., Ltd, Xi'an Hi-tech Industrial Development Zone, Xi'an, 710076, PR China
| | - Shao-Hua Wen
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China
| | - Junping Ma
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China
| | - Yuan Dang
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China.
| | - Jun-Jie Zhu
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China.
| | - Yuanzhen Zhou
- School of Chemistry and Chemical Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China; Engineering Research Center of Low-Carbon Energy Efficient Utilization, Universities of Shaanxi Province, Xi'an University of Architecture and Technology, Xi'an, 710055, PR China.
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Pan Y, Wang D, Wei R, Wang S, Li Y, Pan W, Zhou P, Li N, Tang B. Lateral Flow Platform for Lung Cancer Diagnosis through Simultaneous Detection of ctDNA and MicroRNA. Anal Chem 2025; 97:7063-7070. [PMID: 40162522 DOI: 10.1021/acs.analchem.4c05502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Early cancer screening is essential for reducing cancer-related mortality and improving survival rates. Simultaneous detection of multiple tumor markers can enhance the accuracy and specificity of cancer diagnosis, helping us to mitigate false-positive results associated with single-marker analysis. Here, we have developed a lateral flow detection platform that combines recombinase polymerase amplification (RPA), CRISPR Cas9, and catalyzed hairpin assembly (CHA) for the simultaneous detection of KRAS ctDNA and miRNA-223 in lung cancer. The CRISPR Cas9 system acts as a linking element, enabling specific recognition and binding to RPA amplicons of KRAS ctDNA while facilitating the capture of Au-DNA-Bio nanoparticles (NPs), thereby producing a stronger detection signal through Au NPs aggregation. The CHA system enhances this platform by providing sensitive detection of miRNA-223. Our platform was tested on a limited number of clinical saliva samples, demonstrating feasibility but requiring further validation with larger cohorts.
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Affiliation(s)
- Yingbo Pan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Dawei Wang
- Department of Health Management, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Engineering Laboratory for Health Management, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan 250014, P. R. China
| | - Ruyue Wei
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Shuqi Wang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Yufan Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Wei Pan
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Ping Zhou
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Na Li
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China
- Laoshan Laboratory, Qingdao 266237, P. R. China
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Asefpour Vakilian K. A smart multiplexed microRNA biosensor based on FRET for the prediction of mechanical damage and storage period of strawberry fruits. PLANT MOLECULAR BIOLOGY 2025; 115:37. [PMID: 40011274 DOI: 10.1007/s11103-025-01564-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 02/05/2025] [Indexed: 02/28/2025]
Abstract
Today, measuring the concentration of various microRNAs in fruits has been introduced to model the storage conditions of agricultural products. However, there is a limiting factor in the extensive utilization of such techniques: the existing methods for measuring microRNA sequences, including PCR and microarrays, are time-consuming and expensive and do not allow for simultaneous measurement of several microRNAs. In this study, a biosensor based on the Förster resonance energy transfer (FRET) of fluorescence dyes that can lead to the hybridization of oligonucleotide probes labeled with such dyes by using an excitation wavelength has been used to simultaneously measure microRNAs. Three microRNA compounds, i.e., miRNA-164, miRNA-167, and miRNA-399a, which play significant roles in the postharvest characteristics of strawberry fruits were measured. The simultaneous measurement was performed using three fluorescence dyes which exert various emission wavelengths at 570, 596, and 670 nm. In the following, machine learning methods including artificial neural networks (ANNs) and support vector machines (SVMs), with hyperparameter values optimized with the help of metaheuristic optimization algorithms, were used to predict the amount of mechanical loading on strawberry fruits and their storage period having the microRNA concentrations. The results showed that the SVM with Gaussian kernel, which was optimized by the Harris hawks optimization, is capable of predicting the mechanical stress and storage period of strawberry fruits with a coefficient of determination (R2) of 0.89 and 0.92, respectively. The findings of this study reveal the application of combining FRET-based biosensors and machine learning methods in fruit storage quality assessment.
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Affiliation(s)
- Keyvan Asefpour Vakilian
- Department of Biosystems Engineering, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran.
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4
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Forbes LM, Bauer N, Bhadra A, Bogaard HJ, Choudhary G, Goss KN, Gräf S, Heresi GA, Hopper RK, Jose A, Kim Y, Klouda T, Lahm T, Lawrie A, Leary PJ, Leopold JA, Oliveira SD, Prisco SZ, Rafikov R, Rhodes CJ, Stewart DJ, Vanderpool RR, Yuan K, Zimmer A, Hemnes AR, de Jesus Perez VA, Wilkins MR. Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series). Pulm Circ 2025; 15:e70027. [PMID: 39749110 PMCID: PMC11693987 DOI: 10.1002/pul2.70027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 11/25/2024] [Accepted: 12/02/2024] [Indexed: 01/04/2025] Open
Abstract
Pulmonary vascular disease is not a single condition; rather it can accompany a variety of pathologies that impact the pulmonary vasculature. Applying precision medicine strategies to better phenotype, diagnose, monitor, and treat pulmonary vascular disease is increasingly possible with the growing accessibility of powerful clinical and research tools. Nevertheless, challenges exist in implementing these tools to optimal effect. The 2023 Grover Conference Series reviewed the research landscape to summarize the current state of the art and provide a better understanding of the application of precision medicine to managing pulmonary vascular disease. In particular, the following aspects were discussed: (1) Clinical phenotypes, (2) genetics, (3) epigenetics, (4) biomarker discovery, (5) application of precision biology to clinical trials, (6) the right ventricle (RV), and (7) integrating precision medicine to clinical care. The present review summarizes the content of these discussions and the prospects for the future.
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Affiliation(s)
- Lindsay M. Forbes
- Division of Pulmonary Sciences and Critical Care MedicineUniversity of ColoradoAuroraColoradoUSA
| | - Natalie Bauer
- Department of PharmacologyCollege of Medicine, University of South AlabamaMobileAlabamaUSA
- Department of Physiology and Cell BiologyUniversity of South AlabamaMobileAlabamaUSA
| | - Aritra Bhadra
- Department of PharmacologyCollege of Medicine, University of South AlabamaMobileAlabamaUSA
- Center for Lung BiologyCollege of Medicine, University of South AlabamaMobileAlabamaUSA
| | - Harm J. Bogaard
- Department of Pulmonary MedicineAmsterdam UMCAmsterdamNetherlands
| | - Gaurav Choudhary
- Division of CardiologyWarren Alpert Medical School of Brown UniversityProvidenceRhode IslandUSA
- Lifespan Cardiovascular InstituteRhode Island and Miriam HospitalsProvidenceRhode IslandUSA
- Department of CardiologyProvidence VA Medical CenterProvidenceRhode IslandUSA
| | - Kara N. Goss
- Department of Medicine and PediatricsUniversity of Texas Southwestern Medical CenterDallasTexasUSA
| | - Stefan Gräf
- Division of Computational Genomics and Genomic Medicine, Department of MedicineUniversity of Cambridge, Victor Phillip Dahdaleh Heart & Lung Research InstituteCambridgeUK
| | | | - Rachel K. Hopper
- Department of PediatricsStanford University School of MedicinePalo AltoCaliforniaUSA
| | - Arun Jose
- Division of Pulmonary, Critical Care, and Sleep MedicineUniversity of CincinnatiCincinnatiOhioUSA
| | - Yunhye Kim
- Division of Pulmonary MedicineBoston Children's HospitalBostonMAUSA
| | - Timothy Klouda
- Division of Pulmonary MedicineBoston Children's HospitalBostonMAUSA
| | - Tim Lahm
- Division of Pulmonary Sciences and Critical Care MedicineUniversity of ColoradoAuroraColoradoUSA
- Division of Pulmonary, Critical Care, and Sleep MedicineNational Jewish HealthDenverColoradoUSA
- Pulmonary and Critical Care SectionRocky Mountain Regional VA Medical CenterDenverColoradoUSA
| | - Allan Lawrie
- National Heart and Lung InstituteImperial College LondonLondonUK
| | - Peter J. Leary
- Departments of Medicine and EpidemiologyUniversity of WashingtonSeattleWashingtonUSA
| | - Jane A. Leopold
- Division of Cardiovascular MedicineBrigham and Women's Hospital, Harvard Medical SchoolBostonMassachusettsUSA
| | - Suellen D. Oliveira
- Department of Anesthesiology, Department of Physiology and BiophysicsUniversity of Illinois at ChicagoChicagoIllinoisUSA
| | - Sasha Z. Prisco
- Division of CardiovascularLillehei Heart Institute, University of MinnesotaMinneapolisMinnesotaUSA
| | - Ruslan Rafikov
- Department of MedicineIndiana UniversityIndianapolisIndianaUSA
| | | | - Duncan J. Stewart
- Ottawa Hospital Research InstituteFaculty of MedicineUniversity of OttawaOttawaOntarioCanada
| | | | - Ke Yuan
- Division of Pulmonary MedicineBoston Children's HospitalBostonMAUSA
| | - Alexsandra Zimmer
- Department of MedicineBrown UniversityProvidenceRhode IslandUSA
- Lifespan Cardiovascular InstituteRhode Island HospitalProvidenceRhode IslandUSA
| | - Anna R. Hemnes
- Division of Allergy, Pulmonary and Critical Care MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Vinicio A. de Jesus Perez
- Division of Pulmonary and Critical Care MedicineStanford University Medical CenterStanfordCaliforniaUSA
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Latifi Z, Nikanfar S, Khodavirdilou R, Beirami SM, Khodavirdilou L, Fattahi A, Oghbaei F. MicroRNAs as diagnostic biomarkers in diabetes male infertility: a systematic review. Mol Biol Rep 2024; 52:90. [PMID: 39739064 DOI: 10.1007/s11033-024-10197-1] [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: 07/11/2024] [Accepted: 12/20/2024] [Indexed: 01/02/2025]
Abstract
This study conducts an in-depth review of the correlation between testis tissue changes and circulating microRNAs (miRNA) in diabetes-induced male reproductive complications, drawing upon both animal and clinical studies. The original articles published in English that specifically investigate miRNAs linked to male infertility in humans or animals with either type I or ΙΙ diabetes mellitus were included. The relevant articles were gathered from the PubMed, Google Scholar, Cochrane Library, and ScienceDirect databases. The quality of study was assessed utilizing the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Prevalence Studies. We collected an overall number of 1989 citations relating to our research subject. Following the elimination of articles based on the criteria, a total of 20 papers were included in the study. Aberrant expression profiles of 25 miRNAs were identified in diabetes associated with male reproductive issues, with 15 miRNAs exhibiting increased expression and 10 miRNAs showing decreased expression. Among the chosen publications, eighteen were identified as low-risk and two were classed as moderate quality. The dysregulated miRNAs were linked to testicular injury, disrupted steroid production, decreased sperm development and quality, and erectile dysfunction. The results demonstrate that the miRNA-mRNA network is linked to the pathological progression of diabetic testicular damage or erectile dysfunction. From a therapeutic perspective, the identification of circulating miRNAs could be beneficial in the timely identification and prevention of diabetes problems, such as diabetes-induced male infertility. Among all signaling pathways influenced by modified miRNAs, the Bax-caspase-3, MAPK, PI3K-Akt, and eNOS-cGMP-PKC were the main deregulated pathways.
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Affiliation(s)
- Zeinab Latifi
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Saba Nikanfar
- Pôle de Recherche en Physiopathologie de la Reproduction, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Rasa Khodavirdilou
- Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center (TTUHSC), Amarillo, TX, USA
| | - Sohrab Minaei Beirami
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Lida Khodavirdilou
- Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center (TTUHSC), Amarillo, TX, USA
| | - Amir Fattahi
- Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Farnaz Oghbaei
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran.
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Chung J, Xiao S, Gao Y, Soung YH. Recent Technologies towards Diagnostic and Therapeutic Applications of Circulating Nucleic Acids in Colorectal Cancers. Int J Mol Sci 2024; 25:8703. [PMID: 39201393 PMCID: PMC11354501 DOI: 10.3390/ijms25168703] [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: 07/12/2024] [Revised: 07/30/2024] [Accepted: 08/05/2024] [Indexed: 09/02/2024] Open
Abstract
Liquid biopsy has emerged as a promising noninvasive approach for colorectal cancer (CRC) management. This review focuses on technologies detecting circulating nucleic acids, specifically circulating tumor DNA (ctDNA) and circulating RNA (cfRNA), as CRC biomarkers. Recent advancements in molecular technologies have enabled sensitive and specific detection of tumor-derived genetic material in bodily fluids. These include quantitative real-time PCR, digital PCR, next-generation sequencing (NGS), and emerging nanotechnology-based methods. For ctDNA analysis, techniques such as BEAMing and droplet digital PCR offer high sensitivity in detecting rare mutant alleles, while NGS approaches provide comprehensive genomic profiling. cfRNA detection primarily utilizes qRT-PCR arrays, microarray platforms, and RNA sequencing for profiling circulating microRNAs and discovering novel RNA biomarkers. These technologies show potential in early CRC detection, treatment response monitoring, minimal residual disease assessment, and tumor evolution tracking. However, challenges remain in standardizing procedures, optimizing detection limits, and establishing clinical utility across disease stages. This review summarizes current circulating nucleic acid detection technologies, their CRC applications, and discusses future directions for clinical implementation.
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Affiliation(s)
| | | | | | - Young Hwa Soung
- Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA; (J.C.); (S.X.); (Y.G.)
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Huang Q, Wang K, Wang Y. Highly sensitive miRNA-21 detection with enzyme-free cascade amplification biosensor. Talanta 2024; 273:125928. [PMID: 38508125 DOI: 10.1016/j.talanta.2024.125928] [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: 12/04/2023] [Revised: 02/17/2024] [Accepted: 03/14/2024] [Indexed: 03/22/2024]
Abstract
In this study, we present an enzyme-free fluorescence biosensor for the highly sensitive detection of miRNA-21, a crucial biomarker in clinical diagnosis. Our innovative approach combines catalytic hairpin assembly (CHA) and entropy-driven amplification into a cascade amplification strategy. MicroRNA initiates the catalytic hairpin assembly reaction, liberating the trigger region needed for the entropy-driven amplification reaction. This triggers a series of strand displacement reactions, resulting in the separation of the fluorescence resonance energy transfer pair and an amplified fluorescence signal from FAM. Our cascade amplification strategy achieves ultra-sensitive microRNA detection, with an impressive limit of detection (LOD) of 1.3 fM, approximately 100-fold lower than CHA alone. Additionally, we successfully applied this biosensor for microRNA quantification in human serum and cell lysates, demonstrating its practicality and potential for early diagnosis.
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Affiliation(s)
- Qiuyan Huang
- School of Chemistry and Enviromental Engineering, Changchun University of Science and Technology, Changchun, 130022, China
| | - Kun Wang
- Department of Physics, New York University, New York, NY, 10003, USA
| | - Yuan Wang
- School of Chemistry and Enviromental Engineering, Changchun University of Science and Technology, Changchun, 130022, China.
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Tian Y, Zhang M, Liu LX, Wang ZC, Liu B, Huang Y, Wang X, Ling YZ, Wang F, Feng X, Tu Y. Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis. Front Immunol 2024; 15:1400744. [PMID: 38799446 PMCID: PMC11116607 DOI: 10.3389/fimmu.2024.1400744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 04/03/2024] [Indexed: 05/29/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.
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Affiliation(s)
- Yu Tian
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
- School of Public Health, Benedictine University, Lisle, IL, United States
| | - Meng Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, China
| | - Li-xia Liu
- Department of Ultrasound, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Zi-chao Wang
- Department of Ultrasound, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Bin Liu
- Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Youcai Huang
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Xiaoling Wang
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Yun-zhi Ling
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Furong Wang
- Department of Pathology, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Xiaoqiang Feng
- Center of Stem Cell and Regenerative Medicine, Gaozhou People’s Hospital, Gaozhou, Guangdong, China
| | - Yanyang Tu
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
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Li Y, Wang J. Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment. BMC Nephrol 2024; 25:140. [PMID: 38649939 PMCID: PMC11034108 DOI: 10.1186/s12882-024-03570-6] [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: 01/25/2024] [Accepted: 04/02/2024] [Indexed: 04/25/2024] Open
Abstract
Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired AKI, which seriously threatens the health of patients. To date, the precise pathogenesis of CI-AKI has remained not clear and may be related to the direct cytotoxicity, hypoxia and ischemia of medulla, and oxidative stress caused by iodine contrast medium, which have diverse physicochemical properties, including cytotoxicity, permeability and viscosity. The latest research shows that microRNAs (miRNAs) are also involved in apoptosis, pyroptosis, and autophagy which caused by iodine contrast medium (ICM), which may be implicated in the pathogenesis of CI-AKI. Unfortunately, effective therapy of CI-AKI is very limited at present. Therefore, effective prevention of CI-AKI is of great significance, and several preventive options, including hydration, antagonistic vasoconstriction, and antioxidant drugs, have been developed. Here, we review current knowledge about the features of iodine contrast medium, the definition, pathogenesis, molecular mechanism, risk factors, prevention and treatment of CI-AKI.
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Affiliation(s)
- Yanyan Li
- Department of Pharmacy, Chongqing Traditional Chinese Medicine Hospital, 400021, Chongqing, P.R. China
| | - Junda Wang
- Department of Radiology, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi 7 Branch Road, 400021, Chongqing, P.R. China.
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10
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Akbar S, Mashreghi S, Kalani MR, Valanik A, Ahmadi F, Aalikhani M, Bazi Z. Blood miRNAs miR-549a, miR-552, and miR-592 serve as potential disease-specific panels to diagnose colorectal cancer. Heliyon 2024; 10:e28492. [PMID: 38571665 PMCID: PMC10988015 DOI: 10.1016/j.heliyon.2024.e28492] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/05/2024] Open
Abstract
Introduction miRNAs originating from colorectal cancer (CRC) tissue receive significant focus in the early diagnosis of CRC due to their stability in body fluids. However, if these miRNAs originated from alternative organs, their prognostic value will diminish. Thus, in this study, we aim to identify disease-specific miRNAs for colorectal cancer (CRC) by employing bioinformatics and experimental methodologies. Method To identify CRC-specific miRNAs, we retrieved miRNA profiles of CRC and normal tissues from the Cancer Genome Atlas (TCGA) database. Subsequently, computational strategies were utilized to select potential candidate miRNAs. Following this, the expression levels of the potent miRNAs were assessed through RT-qPCR in both CRC tissue and serum samples from patients (N = 46), as well as healthy individuals (N = 46). Additionally, the associations between clinicopathological characteristics, survival outcomes, and diagnostic accuracy were evaluated. Results A total of 8893 RNA-seq expression data were acquired from TCGA, comprising 8250 data from 19 distinct cancer types and 643 corresponding healthy samples. Based on the computational methodology, miR-549a, miR-552, and miR-592 were identified as the principal expressed miRNAs in colorectal cancer (CRC). Within these miRNAs, miR-552 displayed a substantial association with tumors at the N and T stages. miR-549a and miR-592 were observed to be linked exclusively to the invasion of tumor depth and tumor stage (TNM), respectively. The receiver operating characteristic (ROC) analysis conducted on the miRNA expression in serum samples revealed that all miRNAs exhibited an area under the ROC curve (AUC) of up to 0.86, thereby indicating their high diagnostic accuracy. Conclusion Considering the strong associations of these three identified miRNAs with CRC, they can collectively serve as a panel for specific discrimination of CRC from other types of cancer within the body. Although this study focused solely on CRC, this approach can potentially be applied to other cancer types as well.
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Affiliation(s)
- Soroush Akbar
- Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Samaneh Mashreghi
- Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran
| | | | - Akram Valanik
- Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran
| | - Farzaneh Ahmadi
- Department of Biostatistics and Epidemiology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahdi Aalikhani
- Department of Medical Biotechnology, School of Allied Medical Sciences, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Zahra Bazi
- Department of Medical Biotechnology, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran
- Cancer Research Center, Golestan University of Medical Sciences, Gorgan, Iran
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11
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Guo H, Chen J, Feng Y, Dai Z. A Simple and Robust Exponential Amplification Reaction (EXPAR)-Based Hairpin Template (exp-Hairpin) for Highly Specific, Sensitive, and Universal MicroRNA Detection. Anal Chem 2024; 96:2643-2650. [PMID: 38295438 DOI: 10.1021/acs.analchem.3c05323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
Specific and sensitive detection of microRNAs continues to encounter significant challenges, especially in the development of rapid and efficient isothermal amplification strategies for point-of-care settings. The exponential amplification reaction (EXPAR) has garnered significant attention owing to its simplicity and rapid amplification of signals within a short period. However, a substantial loss of amplification efficiency, difficulty in distinguishing closely related homologous sequences, and adapting the designed templates to other targets seriously hamper the practical application of the EXPAR. In this work, a hairpin template tailored for the EXPAR system (exp-Hairpin) was constructed by adding identical trigger sequences and enzyme cleavage sites on two arms of the hairpin, achieving theoretically more than 2n amplification efficiency and minimal background amplification of EXPAR. Modulating the stability of the exp-Hairpin template by increasing the stem length, the specificity of detecting target miRNA in highly homologous sequences could be significantly improved. Using miRNA let-7a as a target model, the exp-Hairpin with 8 bp stem length for EXPAR amplification curves could effectively distinguish target let-7a and nontarget let-7b/7c/7f/7g/7i homologous sequences. This strategy enabled the sensitive and accurate analysis of let-7a in diluted human serum with satisfactory recoveries. By simply replacing the loop recognition sequence of exp-Hairpin, the specific detection of miR-200b was also achieved, demonstrating the universality of this strategy. The exp-Hairpin EXPAR accelerates simple and rapid molecular diagnostic applications for short nucleic acids.
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Affiliation(s)
- Haijing Guo
- College of Chemistry and Materials Science, Northwest University, Xi'an 710127, PR China
| | - Jun Chen
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China
| | - Yaqiang Feng
- College of Chemistry and Materials Science, Northwest University, Xi'an 710127, PR China
| | - Zong Dai
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou 510006, PR China
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12
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Li D, Yao Y, Cheng W, Hou Z, Wang Z, Xiang Y. Self-Priming Cyclic Amplification Accelerating CRISPR Sensor for Sensitive and Specific MicroRNA Analysis with No Background. Anal Chem 2024; 96:1717-1724. [PMID: 38217876 DOI: 10.1021/acs.analchem.3c04866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2024]
Abstract
In this work, we demonstrate for the first time the application of the phosphorothioated-terminal hairpin formation and self-priming extension (PS-THSP) reaction for miRNA assays. A self-priming amplification accelerating CRISPR sensor was well-established for sensitive and specific miRNA detection by integrating the PS-THSP reaction and CRISPR/Cas12a system. The sensor consists of three steps: (1) the formation of a complete PS-THSP template in the presence of target miRNA and ligase; (2) the exponential isothermal amplification of the PS-THSP reaction under the action of DNA polymerase; (3) the activation of the CRISPR/Cas12a fluorescence system to generate signals. We used miR-21 as a model target. The sensor can achieve sensitive detection of miR-21 without the involvement of any primers, and the special design of the CRISPR proto-spacer neighbor motif (PAM) sequence effectively avoids the interference of the background signal. In addition, the sensor can not only identify single-base mutant homologous sequences but also show stable performance in complex biological matrices. We have successfully used this sensor to accurately analyze miR-21 in different cell lines and real clinical samples, demonstrating its great potential in clinical diagnosis.
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Affiliation(s)
- Dayong Li
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China
| | - Yanheng Yao
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China
| | - Wenting Cheng
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China
| | - Zhiqiang Hou
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China
| | - Zhongyun Wang
- Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P. R. China
| | - Yang Xiang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China
- State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, P. R. China
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13
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Mohammadi P, Asefpour Vakilian K. Machine learning provides specific detection of salt and drought stresses in cucumber based on miRNA characteristics. PLANT METHODS 2023; 19:123. [PMID: 37940966 PMCID: PMC10631058 DOI: 10.1186/s13007-023-01095-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 10/19/2023] [Indexed: 11/10/2023]
Abstract
BACKGROUND Specific detection of the type and severity of plant abiotic stresses helps prevent yield loss by considering timely actions. This study introduces a novel method to detect the type and severity of stress in cucumber plants under salinity and drought conditions. Various features, i.e., morphological (image textural features), physiological/biochemical (relative water content, chlorophyll, catalase activity, anthocyanins, phenol content, and proline), as well as miRNA characteristics (the concentration of miRNA-156a, miRNA-166i, miRNA-399g, and miRNA-477b) were extracted from plant leaves, and machine learning methods were used to predict the type and severity of stress by having these features. Support vector machine (SVM) with parameters optimized by genetic algorithm (GA) and particle swarm optimization (PSO) was used for machine learning. RESULTS The coefficient of determination of predicting the stress type and severity in plants under both stresses was 0.61, 0.82, and 0.99 using morphological, physiological/biochemical, and miRNA characteristics, respectively. This reveals machine learning methods optimized by metaheuristic optimization techniques can provide specific detection of salt and drought stresses in cucumber plants based on miRNA characteristics. Among the study miRNAs, miRNA-477b and miRNA-399g had the highest and lowest contribution to salt and drought stresses, respectively. CONCLUSIONS Comapred to conventional plant traits, miRNAs are more reliable features for providing us with valuable information about plant abiotic diseases at early stages. Using an electrochemical miRNA biosensor similar to one used in this work to measure the miRNA concentration in plant leaves and using a machine learning algorithm such as SVM enable farmers to detect the salt and drought stress at early stages in cucumber plants with very high accuracy.
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Affiliation(s)
- Parvin Mohammadi
- Department of Agrotechnology, College of Abouraihan, University of Tehran, Tehran, Iran
| | - Keyvan Asefpour Vakilian
- Department of Biosystems Engineering, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran.
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14
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Ranković B, Hauptman N. Circulating microRNA Panels for Detection of Liver Cancers and Liver-Metastasizing Primary Cancers. Int J Mol Sci 2023; 24:15451. [PMID: 37895131 PMCID: PMC10607808 DOI: 10.3390/ijms242015451] [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: 09/29/2023] [Revised: 10/14/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
Malignant liver tumors, including primary malignant liver tumors and liver metastases, are among the most frequent malignancies worldwide. The disease carries a poor prognosis and poor overall survival, particularly in cases involving liver metastases. Consequently, the early detection and precise differentiation of malignant liver tumors are of paramount importance for making informed decisions regarding patient treatment. Significant research efforts are currently directed towards the development of diagnostic tools for different types of cancer using minimally invasive techniques. A prominent area of focus within this research is the evaluation of circulating microRNA, for which dysregulated expression is well documented in different cancers. Combining microRNAs in panels using serum or plasma samples derived from blood holds great promise for better sensitivity and specificity for detection of certain types of cancer.
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Affiliation(s)
| | - Nina Hauptman
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia;
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15
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Wang K, Wang X, Pan Q, Zhao B. Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation. Mol Cancer 2023; 22:167. [PMID: 37803304 PMCID: PMC10557192 DOI: 10.1186/s12943-023-01870-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 09/25/2023] [Indexed: 10/08/2023] Open
Abstract
Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.
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Affiliation(s)
- Kangchun Wang
- Department of Organ Transplantation and Hepatobiliary, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
| | - Xin Wang
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Qi Pan
- Department of Organ Transplantation and Hepatobiliary, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
| | - Bei Zhao
- Department of Ultrasound, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
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16
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Abidin SZ, Mat Pauzi NA, Mansor NI, Mohd Isa NI, Hamid AA. A new perspective on Alzheimer's disease: microRNAs and circular RNAs. Front Genet 2023; 14:1231486. [PMID: 37790702 PMCID: PMC10542399 DOI: 10.3389/fgene.2023.1231486] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/25/2023] [Indexed: 10/05/2023] Open
Abstract
microRNAs (miRNAs) play a multifaceted role in the pathogenesis of Alzheimer's disease (AD). miRNAs regulate several aspects of the disease, such as Aβ metabolism, tau phosphorylation, neuroinflammation, and synaptic function. The dynamic interaction between miRNAs and their target genes depends upon various factors, including the subcellular localization of miRNAs, the relative abundance of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. The miRNAs are released into extracellular fluids and subsequently conveyed to specific target cells through various modes of transportation, such as exosomes. In comparison, circular RNAs (circRNAs) are non-coding RNA (ncRNA) characterized by their covalently closed continuous loops. In contrast to linear RNA, RNA molecules are circularized by forming covalent bonds between the 3'and 5'ends. CircRNA regulates gene expression through interaction with miRNAs at either the transcriptional or post-transcriptional level, even though their precise functions and mechanisms of gene regulation remain to be elucidated. The current stage of research on miRNA expression profiles for diagnostic purposes in complex disorders such as Alzheimer's disease is still in its early phase, primarily due to the intricate nature of the underlying pathological causes, which encompass a diverse range of pathways and targets. Hence, this review comprehensively addressed the alteration of miRNA expression across diverse sources such as peripheral blood, exosome, cerebrospinal fluid, and brain in AD patients. This review also addresses the nascent involvement of circRNAs in the pathogenesis of AD and their prospective utility as biomarkers and therapeutic targets for these conditions in future research.
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Affiliation(s)
- Shahidee Zainal Abidin
- Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Terengganu, Malaysia
- Biological Security and Sustainability (BIOSIS) Research Interest Group, Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Terengganu, Malaysia
| | - Nurul Asykin Mat Pauzi
- Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Terengganu, Malaysia
| | - Nur Izzati Mansor
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nurul Iffah Mohd Isa
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Adila A. Hamid
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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17
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Rasizadeh R, Aghbash PS, Nahand JS, Entezari-Maleki T, Baghi HB. SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs. Virol J 2023; 20:179. [PMID: 37559103 PMCID: PMC10413769 DOI: 10.1186/s12985-023-02152-6] [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: 01/28/2023] [Accepted: 08/04/2023] [Indexed: 08/11/2023] Open
Abstract
SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.
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Affiliation(s)
- Reyhaneh Rasizadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parisa Shiri Aghbash
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javid Sadri Nahand
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taher Entezari-Maleki
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran.
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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18
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Shibamoto J, Arita T, Konishi H, Kataoka S, Furuke H, Takaki W, Kiuchi J, Shimizu H, Yamamoto Y, Komatsu S, Shiozaki A, Kuriu Y, Otsuji E. Roles of miR-4442 in Colorectal Cancer: Predicting Early Recurrence and Regulating Epithelial-Mesenchymal Transition. Genes (Basel) 2023; 14:1414. [PMID: 37510319 PMCID: PMC10378884 DOI: 10.3390/genes14071414] [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: 05/26/2023] [Revised: 07/05/2023] [Accepted: 07/07/2023] [Indexed: 07/30/2023] Open
Abstract
Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing preoperative and postoperative plasma levels in patients with CRC, with and without recurrence. The association between preoperative plasma miR-4442 levels, clinicopathological features, and recurrence-free survival was analyzed in 108 patients with CRC after curative surgery. Furthermore, cell-function analyses were performed, and the involvement of miR-4442 in regulating epithelial-mesenchymal transition (EMT) was examined. Preoperatively plasma miR-4442 levels were associated with CRC recurrence and exhibited an incremental increase with earlier recurrence dates. Moreover, miR-4442 demonstrated high sensitivity and specificity as a potential biomarker for early CRC recurrence. The expression of miR-4442 in cancer tissues of patients with metastatic liver cancer from CRC was higher than in normal liver, CRC, and normal colorectal tissues. The overexpression of miR-4442 promoted the proliferative, migratory, and invasive activities of CRC cells, decreased levels of RBMS1 and E-cadherin, and increased levels of N-cadherin and Snail1. Plasma miR-4442 is a clinically useful biomarker for predicting the early recurrence of CRC. Furthermore, miR-4442 regulates EMT in CRC by directly targeting the messenger RNA of RBMS1.
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Affiliation(s)
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
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19
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Wang Y, Zhang J, He Y, Pan Z, Zhang X, Liu P, Hu K. The theranostic value of acetylation gene signatures in obstructive sleep apnea derived by machine learning. Comput Biol Med 2023; 161:107058. [PMID: 37244148 DOI: 10.1016/j.compbiomed.2023.107058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 05/09/2023] [Accepted: 05/20/2023] [Indexed: 05/29/2023]
Abstract
Epigenetic modifications are implicated in the onset and progression of obstructive sleep apnea (OSA) and its complications through their bidirectional relationship with long-term chronic intermittent hypoxia (IH). However, the exact role of epigenetic acetylation in OSA is unclear. Here we explored the relevance and impact of acetylation-related genes in OSA by identifying molecular subtypes modified by acetylation in OSA patients. Twenty-nine significantly differentially expressed acetylation-related genes were screened in a training dataset (GSE135917). Six common signature genes were identified using the lasso and support vector machine algorithms, with the powerful SHAP algorithm used to judge the importance of each identified feature. DSCC1, ACTL6A, and SHCBP1 were best calibrated and discriminated OSA patients from normal in both training and validation (GSE38792) datasets. Decision curve analysis showed that patients could benefit from a nomogram model developed using these variables. Finally, a consensus clustering approach characterized OSA patients and analyzed the immune signatures of each subgroup. OSA patients were divided into two acetylation patterns (higher acetylation scores in Group B than in Group A) that differed significantly in terms of immune microenvironment infiltration. This is the first study to reveal the expression patterns and key role played by acetylation in OSA, laying the foundation for OSA epitherapy and refined clinical decision-making.
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Affiliation(s)
- Yixuan Wang
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Jingyi Zhang
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Yang He
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Zhou Pan
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Xinyue Zhang
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Peijun Liu
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Ke Hu
- Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
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20
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Studies on the application of single-stranded DNA and PNA probes for electrochemical detection of miRNA 141. Bioelectrochemistry 2023; 150:108363. [PMID: 36608369 DOI: 10.1016/j.bioelechem.2022.108363] [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: 04/06/2022] [Revised: 12/09/2022] [Accepted: 12/28/2022] [Indexed: 12/31/2022]
Abstract
The abnormal concentration of microRNAs (miRNAs) can be associated with occurrence of various diseases including cancer, cardiovascular and neurodegenerative, hence they can be considered as potential biomarkers. An attractive approach could be the application of electrochemical methods, particularly where hybridization event between single-stranded deoxyribonucleic acid (ssDNA) or peptide-nucleic acid (PNA) with miRNA strand happens. Recently, the use of various nanomaterials such as gold nanoparticles, graphene oxide, quantum dots as well as catalyzed hairpin assembly or hybridization chain reaction were proposed to further enhance the performance of elaborated sensors. Herein, we present the studies on selection of receptor layer composition for detection of miRNA 141. The possibility of formation of receptor layer and further duplex monolayer between ssDNA or PNA with miRNA was analyzed by atomic force microscopy (AFM) technique. The interaction of ssDNA and PNA probes with miRNA was further verified using surface plasmon resonance (SPR) and quartz - crystal microbalance (QCM) techniques. On the basis of impedance spectroscopy it was shown that the use of unlabelled ssDNA as receptor layer provided 0.1 pM detection limit. This shows that proposed biosensor that is simple in preparation and use is an attractive alternative to other recently presented approaches.
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21
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Zeng H, Zhou H, Lin J, Pang Q, Chen S, Lin S, Xue C, Shen Z. Palindrome-Embedded Hairpin Structure and Its Target-Catalyzed Padlock Cyclization for Label-Free MicroRNA-Initiated Rolling Circle Amplification. ACS OMEGA 2023; 8:2253-2261. [PMID: 36687024 PMCID: PMC9850459 DOI: 10.1021/acsomega.2c06532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 12/19/2022] [Indexed: 06/17/2023]
Abstract
Highly sensitive detection of microRNAs (miRNAs) is of great significance in early diagnosis of cancers. Here, we develop a palindrome-embedded hairpin structure and its target-catalyzed padlock cyclization for rolling circle amplification, named PHP-RCA for simplicity, which can be applied in label-free ultrasensitive detection of miRNA. PHP-RCA is a facile system that consists of only an oligonucleotide probe with a palindrome-embedded hairpin structure (PHP). The two ends of PHP were extended as overhangs and designed with the complementary sequences of the target. Hence, the phosphorylated PHP can be cyclized by T4 DNA ligase in the presence of the target that serves as the ligation template. This ligation has formed a palindrome-embedded dumbbell-shaped probe (PDP) that allows phi29 polymerase to perform a typical target-primed RCA on PDP by taking miRNA as a primer, resulting in the production of a lengthy tandem repeat. Benefits from the palindromic sequences and hairpin-shaped structure in padlock double-stranded structures can be infinitely produced during the RCA reaction and provide numerous binding sites for SYBR Green I, a double-stranded dye, achieving a sharp response signal for label-free target detection. We have demonstrated that the proposed system exhibits a good linear range from 0.1 fM to 5 nM with a low detection limit of 0.1 fM, and the non-target miRNA can be clearly distinguished. The advantages of high efficiency, label-free signaling, and the use of only one oligonucleotide component make the PHP-RCA suitable for ultrasensitive, economic, and convenient detection of target miRNAs. This simple and powerful system is expected to provide a promising platform for tumor diagnosis, prognosis, and therapy.
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Affiliation(s)
- Huaiwen Zeng
- Yuhuan
People’s Hospital, Taizhou Zhejiang Province, Taizhou 317600, PR China
| | - Hongyin Zhou
- Key
Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang
Provincial Key Laboratory of Medical Genetics, Department of Cell
Biology and Medical Genetics, College of Laboratory Medicine and Life
Sciences, Wenzhou Medical University, Wenzhou 325000, PR China
| | - Junliang Lin
- Yuhuan
People’s Hospital, Taizhou Zhejiang Province, Taizhou 317600, PR China
| | - Qi Pang
- Yuhuan
People’s Hospital, Taizhou Zhejiang Province, Taizhou 317600, PR China
| | - Siqiang Chen
- Yuhuan
People’s Hospital, Taizhou Zhejiang Province, Taizhou 317600, PR China
| | - Shaoqi Lin
- Yuhuan
People’s Hospital, Taizhou Zhejiang Province, Taizhou 317600, PR China
| | - Chang Xue
- Key
Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang
Provincial Key Laboratory of Medical Genetics, Department of Cell
Biology and Medical Genetics, College of Laboratory Medicine and Life
Sciences, Wenzhou Medical University, Wenzhou 325000, PR China
| | - Zhifa Shen
- Key
Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang
Provincial Key Laboratory of Medical Genetics, Department of Cell
Biology and Medical Genetics, College of Laboratory Medicine and Life
Sciences, Wenzhou Medical University, Wenzhou 325000, PR China
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22
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Motshwari DD, Matshazi DM, Erasmus RT, Kengne AP, Matsha TE, George C. MicroRNAs Associated with Chronic Kidney Disease in the General Population and High-Risk Subgroups-A Systematic Review. Int J Mol Sci 2023; 24:ijms24021792. [PMID: 36675311 PMCID: PMC9863068 DOI: 10.3390/ijms24021792] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/09/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
The potential utility of microRNAs (miRNAs) as diagnostic or prognostic biomarkers, as well as therapeutic targets, for chronic kidney disease (CKD) has been advocated. However, studies evaluating the expression profile of the same miRNA signatures in CKD report contradictory findings. This review aimed to characterize miRNAs associated with CKD and/or measures of kidney function and kidney damage in the general population, and also in high-risk subgroups, including people with hypertension (HTN), diabetes mellitus (DM) and human immunodeficiency virus (HIV) infection. Medline via PubMed, Scopus, Web of Science, and EBSCOhost databases were searched to identify relevant studies published in English or French languages on or before 30 September 2022. A total of 75 studies fulfilled the eligibility criteria: CKD (n = 18), diabetic kidney disease (DKD) (n = 51) and HTN-associated CKD (n = 6), with no study reporting on miRNA profiles in people with HIV-associated nephropathy. In individuals with CKD, miR-126 and miR-223 were consistently downregulated, whilst in DKD, miR-21 and miR-29b were consistently upregulated and miR-30e and let-7a were consistently downregulated in at least three studies. These findings suggest that these miRNAs may be involved in the pathogenesis of CKD and therefore invites further research to explore their clinical utility for CKD prevention and control.
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Affiliation(s)
- Dipuo D. Motshwari
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town 7530, South Africa
| | - Don M. Matshazi
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town 7530, South Africa
| | - Rajiv T. Erasmus
- Division of Chemical Pathology, Faculty of Medicine and Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town 7505, South Africa
| | - Andre P. Kengne
- Non-Communicable Disease Research Unit, South African Medical Research Council, Parow, Cape Town 7505, South Africa
- Department of Medicine, University of Cape Town, Cape Town 7925, South Africa
| | - Tandi E. Matsha
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town 7530, South Africa
- Sefako Makgatho Health Sciences University, Ga-Rankuwa 0208, South Africa
| | - Cindy George
- Non-Communicable Disease Research Unit, South African Medical Research Council, Parow, Cape Town 7505, South Africa
- Correspondence:
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MicroRNAs: Small Molecules with Significant Functions, Particularly in the Context of Viral Hepatitis B and C Infection. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59010173. [PMID: 36676797 PMCID: PMC9862007 DOI: 10.3390/medicina59010173] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023]
Abstract
A MicroRNA (miRNA) is defined as a small molecule of non-coding RNA (ncRNA). Its molecular size is about 20 nucleotides (nt), and it acts on gene expression's regulation at the post-transcription level through binding to the 3'untranslated regions (UTR), coding sequences, or 5'UTR of the target messenger RNAs (mRNAs), which leads to the suppression or degradation of the mRNA. In recent years, a huge evolution has identified the origin and function of miRNAs, focusing on their important effects in research and clinical applications. For example, microRNAs are key players in HCV infection and have important host cellular factors required for HCV replication and cell growth. Altered expression of miRNAs affects the pathogenicity associated with HCV infection through regulating different signaling pathways that control HCV/immunity interactions, proliferation, and cell death. On the other hand, circulating miRNAs can be used as novel biomarkers and diagnostic tools for HCV pathogenesis and early therapeutic response. Moreover, microRNAs (miRNA) have been involved in hepatitis B virus (HBV) gene expression and advanced antiviral discovery. They regulate HBV/HCV replication and pathogenesis with different pathways involving facilitation, inhibition, activation of the immune system (innate and adaptive), and epigenetic modifications. In this short review, we will discuss how microRNAs can be used as prognostic, diagnostic, and therapeutic tools, especially for chronic hepatitis viruses (HBV and HCV), as well as how they could be used as new biomarkers during infection and advanced treatment.
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Kim N, Choung H, Kim YJ, Woo SE, Yang MK, Khwarg SI, Lee MJ. Serum microRNA as a potential biomarker for the activity of thyroid eye disease. Sci Rep 2023; 13:234. [PMID: 36604580 PMCID: PMC9816116 DOI: 10.1038/s41598-023-27483-w] [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: 06/24/2022] [Accepted: 01/03/2023] [Indexed: 01/06/2023] Open
Abstract
The aim of this study is to characterize the microRNA (miRNA) expression signatures in patients with thyroid eye disease (TED) and identify miRNA biomarkers of disease activity. Total RNA was isolated from the sera of patients with TED (n = 10) and healthy controls (HCs, n = 5) using the miRNeasy Serum/Plasma Kit. The NanoString assay was used for the comprehensive analysis of 798 miRNA expression profiles. Analysis of specific miRNA signatures, mRNA target pathway analysis, and network analysis were performed. Patients with TED were divided into two groups according to disease activity: active and inactive TED groups. Differentially expressed circulating miRNAs were identified and tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) tests in the validation cohort. Among the 798 miRNAs analyzed, 173 differentially downregulated miRNAs were identified in TED patients compared to those in the HCs. Ten circulating miRNAs were differentially expressed between the active and inactive TED groups and regarded as candidate biomarkers for TED activity (one upregulated miRNA: miR-29c-3p; nine downregulated miRNAs: miR-4286, miR-941, miR-571, miR-129-2-3p, miR-484, miR-192-5p, miR-502-3p, miR-597-5p, and miR-296-3p). In the validation cohort, miR-484 and miR-192-5p showed significantly lower expression in the active TED group than in the inactive TED group. In conclusion, the expression levels of miR-484 and miR-192-5p differed significantly between the active and inactive TED groups, suggesting that these miRNAs could serve as circulating biomarkers of TED activity, however, these findings need to be validated in further studies.
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Affiliation(s)
- Namju Kim
- grid.412480.b0000 0004 0647 3378Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hokyung Choung
- grid.412479.dDepartment of Ophthalmology, Seoul Metropolitan Government-Seoul National University, Boramae Medical Center, Seoul, Korea ,grid.31501.360000 0004 0470 5905Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea
| | - Yu Jeong Kim
- grid.412484.f0000 0001 0302 820XDepartment of Ophthalmology, Seoul National University Hospital, Seoul, Korea
| | - Sang Earn Woo
- grid.412479.dDepartment of Ophthalmology, Seoul Metropolitan Government-Seoul National University, Boramae Medical Center, Seoul, Korea
| | - Min Kyu Yang
- grid.413967.e0000 0001 0842 2126Department of Ophthalmology, Asan Medical Center, Seoul, Korea
| | - Sang In Khwarg
- grid.31501.360000 0004 0470 5905Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea ,grid.412484.f0000 0001 0302 820XDepartment of Ophthalmology, Seoul National University Hospital, Seoul, Korea
| | - Min Joung Lee
- Department of Ophthalmology, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-Ro 170 Beon-Gil, Dongan-Gu, Anyang-Si, Gyeonggi-Do, 14068, Republic of Korea.
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25
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El-Daly SM, Gouhar SA, Abd Elmageed ZY. Circulating microRNAs as Reliable Tumor Biomarkers: Opportunities and Challenges Facing Clinical Application. J Pharmacol Exp Ther 2023; 384:35-51. [PMID: 35809898 PMCID: PMC9827506 DOI: 10.1124/jpet.121.000896] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 01/13/2023] Open
Abstract
MicroRNAs (miRNAs) are involved in the development of human malignancies, and cells have the ability to secrete these molecules into extracellular compartments. Thus, cell-free miRNAs (circulating miRNAs) can potentially be used as biomarkers to evaluate pathophysiological changes. Although circulating miRNAs have been proposed as potential noninvasive tumor biomarkers for diagnosis, prognosis, and response to therapy, their routine application in the clinic is far from being achieved. This review focuses on the recent progress regarding the value of circulating miRNAs as noninvasive biomarkers, with specific consideration of their relevant clinical applications. In addition, we provide an in-depth analysis of the technical challenges that impact the assessment of circulating miRNAs. We also highlight the significance of integrating circulating miRNAs with the standard laboratory biomarkers to boost sensitivity and specificity. The current status of circulating miRNAs in clinical trials as tumor biomarkers is also covered. These insights and general guidelines will assist researchers in experimental practice to ensure quality standards and repeatability, thus improving future studies on circulating miRNAs. SIGNIFICANCE STATEMENT: Our review will boost the knowledge behind the inconsistencies and contradictory results observed among studies investigating circulating miRNAs. It will also provide a solid platform for better-planned strategies and standardized techniques to optimize the assessment of circulating cell-free miRNAs.
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Affiliation(s)
- Sherien M El-Daly
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Cairo, Egypt (S.M.E-D., S.A.G.); Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt (S.M.E-D.); and Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana-Monroe, Monroe, Louisiana (Z.Y.A.)
| | - Shaimaa A Gouhar
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Cairo, Egypt (S.M.E-D., S.A.G.); Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt (S.M.E-D.); and Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana-Monroe, Monroe, Louisiana (Z.Y.A.)
| | - Zakaria Y Abd Elmageed
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Cairo, Egypt (S.M.E-D., S.A.G.); Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt (S.M.E-D.); and Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana-Monroe, Monroe, Louisiana (Z.Y.A.)
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26
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Diagnostic performance of urine and blood microRNAs for bladder cancer: a meta-analysis. Expert Rev Anticancer Ther 2022; 22:1357-1369. [PMID: 36374119 DOI: 10.1080/14737140.2022.2147511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To compare and assess the diagnostic value of urine and blood microRNAs(miRNAs) in discriminating bladder cancer (BCa). METHODS A total of 45 articles were selected, which included 4050 BCa cases and 3490 controls. Summary receiver operating characteristic (SROC) curve analyses were performed, an area under curve (AUC) was calculated and pooled accuracy was analyzed using Stata 16.0 software. RESULTS The AUC, sensitivity, and specificity for urinary miRNAs were 0.88, 0.82, and 0.81, respectively, those for blood miRNAs were 0.91, 0.86, and 0.82. For miR-143, the AUC was 0.88, with 0.79 sensitivity and 0.87 specificity. The results of subgroup analyses and meta-regression suggested the publication year, ethnicity, sample size, miRNAs type, and specimen type were possible sources of heterogeneity. The Deeks funnel plot indicated there was no significant publication bias. CONCLUSION Urine and blood-based miRNAs may potentially be promising biomarkers for noninvasive early detection of bladder tumor. The diagnostic accuracy of blood-based miRNAs would be better than those of urine-based ones, and multiple miRNA panels yielded more accurate results than single-miRNA assay. Besides, miR-143 is a promising candidate biomarker for diagnosing BCa. More prospective and standardized studies are required to confirm the future findings.
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27
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Galoș D, Gorzo A, Balacescu O, Sur D. Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives. Cells 2022; 11:3493. [PMID: 36359889 PMCID: PMC9657568 DOI: 10.3390/cells11213493] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 10/26/2022] [Accepted: 11/02/2022] [Indexed: 08/13/2023] Open
Abstract
Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis. This review focuses on the potential use of circulating tumor cells (CTCs), circulating nucleic acids (CNAs) and extracellular vesicles as emerging liquid biopsy markers with clinical application in the setting of CRC screening. The review also examines the opportunity to implement liquid biopsy analysis during everyday practice and provides highlights on clinical trials researching blood tests designed for early cancer diagnosis. Additionally, the review explores potential applications of liquid biopsies in the era of immunotherapy.
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Affiliation(s)
- Diana Galoș
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
| | - Alecsandra Gorzo
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
| | - Ovidiu Balacescu
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
| | - Daniel Sur
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
- Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400012 Cluj-Napoca, Romania
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Jiang S, Hu Y, Zhou Y, Tang G, Cui W, Wang X, Chen B, Hu Z, Xu B. miRNAs as Biomarkers and Possible Therapeutic Strategies in Synovial Sarcoma. Front Pharmacol 2022; 13:881007. [PMID: 36003502 PMCID: PMC9394702 DOI: 10.3389/fphar.2022.881007] [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: 02/22/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Synovial sarcoma (SS) is an epithelial-differentiated malignant stromal tumor that has the highest incidence in young people and can occur almost anywhere in the body. Many noncoding RNAs are involved in the occurrence, development, or pathogenesis of SS. In particular, the role of MicroRNAs (miRNAs) in SS is receiving increasing attention. MiRNA is a noncoding RNA abundant in cells and extracellular serums. Increasing evidence suggests that miRNA has played a significant role in the incidence and development of tumors in recent years, including sarcomas. Previous studies show that various sarcomas have their unique miRNA expression patterns and that various miRNA expression profiles can illustrate the classes of miRNAs that may elicit cancer-relevant activities in specific sarcoma subtypes. Furthermore, SS has been reported to have the most number of differentially expressed miRNAs, which indicated that miRNA is linked to SS. In fact, according to many publications, miRNAs have been shown to have a role in the development and appearance of SS in recent years, according to many publications. Since many studies showing that various miRNAs have a role in the development and appearance of SS in recent years have not been systematically summarized, we summarize the recent studies on the relationship between miRNA and SS in this review. For example, miR-494 promotes the development of SS via modulating cytokine gene expression. The role of miR-494-3p as a tumor suppressor is most likely linked to the CXCR4 (C-X-C chemokine receptor 4) regulator, although the exact mechanism is unknown. Our review aims to reveal in detail the potential biological value and clinical significance of miRNAs for SS and the potential clinical value brought by the association between SS and miRNAs.
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Affiliation(s)
- Shaowei Jiang
- Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Ying Hu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China
- School of Pharmacy, Anhui Medical University, Hefei, China
| | - Yi Zhou
- The First Clinical Medical College of Anhui Medical University, Hefei, China
| | - Guozheng Tang
- The First Clinical Medical College of Anhui Medical University, Hefei, China
- Department of Orthopedics, Lu’an People’s Hospital, Lu’an, China
| | - Wenxu Cui
- The First Clinical Medical College of Anhui Medical University, Hefei, China
| | - Xinyi Wang
- The First Clinical Medical College of Anhui Medical University, Hefei, China
| | - Bangjie Chen
- The First Clinical Medical College of Anhui Medical University, Hefei, China
| | - Zuhong Hu
- The First Clinical Medical College of Anhui Medical University, Hefei, China
| | - Bing Xu
- Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Bing Xu,
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29
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Coradduzza D, Solinas T, Balzano F, Culeddu N, Rossi N, Cruciani S, Azara E, Maioli M, Zinellu A, De Miglio MR, Madonia M, Falchi M, Carru C. miRNAs as molecular biomarkers for prostate cancer. J Mol Diagn 2022; 24:1171-1180. [PMID: 35835374 DOI: 10.1016/j.jmoldx.2022.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 04/05/2022] [Accepted: 05/23/2022] [Indexed: 01/10/2023] Open
Abstract
MicroRNAs (miRNAs) are short noncoding RNA able to regulate specific mRNA stability, thus influencing target gene expression. Disrupted levels of several miRNA have been associated with prostate cancer, the leading cause of cancer death among men and the fifth leading cause of death worldwide. Here, we investigated whether miR-145, miR-148, and miR-185 circulating levels in plasma could be used as molecular biomarkers, to allow distinguishing between individuals with benign prostatic hyperplasia, precancerous lesion, and prostate cancer. In this study, we recruited 170 urological clinic patients with suspected prostate cancer who underwent prostate biopsy. Total RNA was isolated from plasma, and TaqMan MicroRNA assays were used to analyze miR-145, miR-185, and miR-148 expression. First, differential miRNA expression among patient groups was evaluated. Then, miRNA levels were combined with clinical assessment outcomes, including results from invasive tests, using multivariate analysis to examine their ability in discriminating among the three patient groups. Our results suggest that miRNA is a promising molecular tool for clinical management of at-risk patients.
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Affiliation(s)
| | - Tatiana Solinas
- Urologic Clinic, Dep. of Clinical and Experimental Medicine, University of Sassari
| | - Francesca Balzano
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Nicola Culeddu
- Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy
| | - Niccolò Rossi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Sara Cruciani
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Emanuela Azara
- Institute of Biomolecular Chemistry, National Research Council, Sassari, Italy
| | - Margherita Maioli
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Angelo Zinellu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | | | - Massimo Madonia
- Urologic Clinic, Dep. of Clinical and Experimental Medicine, University of Sassari
| | - Mario Falchi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Ciriaco Carru
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy; University Hospital of Sassari (AOU), Sassari, Italy.
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30
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Kalhori MR, Soleimani M, Yari K, Moradi M, Kalhori AA. MiR-1290: a potential therapeutic target for regenerative medicine or diagnosis and treatment of non-malignant diseases. Clin Exp Med 2022:10.1007/s10238-022-00854-9. [PMID: 35802264 DOI: 10.1007/s10238-022-00854-9] [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: 04/19/2022] [Accepted: 06/20/2022] [Indexed: 11/03/2022]
Abstract
MicroRNAs are a set of small non-coding RNAs that could change gene expression with post-transcriptional regulation. MiRNAs have a significant role in regulating molecular signaling pathways and innate and adaptive immune system activity. Moreover, miRNAs can be utilized as a powerful instrument for tissue engineers and regenerative medicine by altering the expression of genes and growth factors. MiR-1290, which was first discovered in human embryonic stem cells, is one of those miRNAs that play an essential role in developing the fetal nervous system. This review aims to discuss current findings on miR-1290 in different human pathologies and determine whether manipulation of miR-1290 could be considered a possible therapeutic strategy to treat different non-malignant diseases. The results of these studies suggest that the regulation of miR-1290 may be helpful in the treatment of some bacterial (leprosy) and viral infections (HIV, influenza A, and Borna disease virus). Also, adjusting the expression of miR-1290 in non-infectious diseases such as celiac disease, necrotizing enterocolitis, polycystic ovary syndrome, pulmonary fibrosis, ankylosing spondylitis, muscle atrophy, sarcopenia, and ischemic heart disease can help to treat these diseases better. In addition to acting as a biomarker for the diagnosis of non-malignant diseases (such as NAFLD, fetal growth, preeclampsia, down syndrome, chronic rhinosinusitis, and oral lichen planus), the miR-1290 can also be used as a valuable instrument in tissue engineering and reconstructive medicine. Consequently, it is suggested that the regulation of miR-1290 could be considered a possible therapeutic target in the treatment of non-malignant diseases in the future.
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Affiliation(s)
- Mohammad Reza Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
| | - Masoud Soleimani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Kheirollah Yari
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mahmoudreza Moradi
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amir Ali Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Geropoulos G, Psarras K, Papaioannou M, Giannis D, Meitanidou M, Kapriniotis K, Symeonidis N, Pavlidis ET, Pavlidis TE, Sapalidis K, Ahmed NM, Abdel-Aziz TE, Eddama MMR. Circulating microRNAs and Clinicopathological Findings of Papillary Thyroid Cancer: A Systematic Review. In Vivo 2022; 36:1551-1569. [PMID: 35738604 PMCID: PMC9301440 DOI: 10.21873/invivo.12866] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 04/24/2022] [Accepted: 04/26/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIM Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a rising incidence. There is a need for a non-invasive preoperative test to enable better patient counselling. The aim of this systematic review was to investigate the potential role of circulating microRNAs (miRNAs) in the diagnosis and prognosis of PTC. MATERIALS AND METHODS A systematic literature search was performed using MEDLINE, Cochrane, and Scopus databases (last search date was December 1, 2021). Studies investigating the expression of miRNAs in the serum or plasma of patients with PTC were deemed eligible for inclusion. RESULTS Among the 1,533 screened studies, 39 studies met the inclusion criteria. In total, 108 miRNAs candidates were identified in the serum, plasma, or exosomes of patients suffering from PTC. Furthermore, association of circulating miRNAs with thyroid cancer-specific clinicopathological features, such as tumor size (13 miRNAs), location (3 miRNAs), extrathyroidal extension (9 miRNAs), pre- vs. postoperative period (31 miRNAs), lymph node metastasis (17 miRNAs), TNM stage (9 miRNAs), BRAF V600E mutation (6 miRNAs), serum thyroglobulin levels (2 miRNAs), 131I avid metastases (13 miRNAs), and tumor recurrence (2 miRNAs) was also depicted in this study. CONCLUSION MiRNAs provide a potentially promising role in the diagnosis and prognosis of PTC. There is a correlation between miRNA expression profiles and specific clinicopathological features of PTC. However, to enable their use in clinical practice, further clinical studies are required to validate the predictive value and utility of miRNAs as biomarkers.
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Affiliation(s)
- Georgios Geropoulos
- Department of General and Endocrine Surgery, University College London Hospitals, London, U.K.;
- 2 Propedeutical Department of Surgery, Hippokration Hospital, School of Medicine,Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kyriakos Psarras
- 2 Propedeutical Department of Surgery, Hippokration Hospital, School of Medicine,Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Papaioannou
- Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, Thessaloniki, Greece
| | - Dimitrios Giannis
- Department of Surgery, North Shore University Hospital, Manhasset, NY, U.S.A
| | - Maria Meitanidou
- 2 Propedeutical Department of Surgery, Hippokration Hospital, School of Medicine,Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Nikolaos Symeonidis
- 2 Propedeutical Department of Surgery, Hippokration Hospital, School of Medicine,Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Efstathios T Pavlidis
- 2 Propedeutical Department of Surgery, Hippokration Hospital, School of Medicine,Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodoros E Pavlidis
- 2 Propedeutical Department of Surgery, Hippokration Hospital, School of Medicine,Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantinos Sapalidis
- 3 General Surgery Department, "AHEPA" University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Nada Mabrouk Ahmed
- Department of General and Endocrine Surgery, University College London Hospitals, London, U.K
- Department of Pathology, University of Alexandria, Alexandria, Egypt
| | - Tarek Ezzat Abdel-Aziz
- Department of General and Endocrine Surgery, University College London Hospitals, London, U.K
| | - Mohammad M R Eddama
- Department of General and Endocrine Surgery, University College London Hospitals, London, U.K
- Research Department of Surgical Biotechnology, University College London, London, U.K
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Mao Z, Liu R, Zhang M, Liu W, Li D, Li H. Prognostic and clinicopathological value of miR-199b in cancers: a meta-analysis. Biomark Med 2022; 16:879-888. [PMID: 35704299 DOI: 10.2217/bmm-2022-0138] [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: 12/24/2022] Open
Abstract
Background: The prognostic value of miR-199b in cancers has not been fully clarified. Methods: All articles evaluating the prognostic value of miR-199b in tumors were included. The hazard ratio (HR), odds ratio (OR) and 95% CI were calculated to assess the relationship between miR-199b expression and survival outcomes and clinicopathological features. Results: The combined results indicated that high miR-199b expression predicted favorable overall survival (OS) compared with low miR-199b expression (HR: 0.62, 95% CI: 0.44-0.87). In addition, high miR-199b expression had a significant correlation with the prevention of lymph node metastasis (OR: 0.39, 95% CI: 0.25-0.59). Conclusion: MiR-199b can be used as an effective prognostic marker in cancers.
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Affiliation(s)
- Zhongxiang Mao
- Department of Emergency Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
| | - Rongqiang Liu
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China
| | - Min Zhang
- Department of Anesthesiology, Jiulongpo People's Hospital, Chongqing, 400000, China
| | - Wenbin Liu
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Dewei Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Hui Li
- Department of Hepatobiliary Pancreatic Tumor Center, Chongqing University Cancer Hospital, Chongqing, 400030, China
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Cao S, Tang X, Chen T, Chen G. Types and Applications of Nicking Enzyme-Combined Isothermal Amplification. Int J Mol Sci 2022; 23:ijms23094620. [PMID: 35563012 PMCID: PMC9100243 DOI: 10.3390/ijms23094620] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/03/2022] [Accepted: 04/11/2022] [Indexed: 02/01/2023] Open
Abstract
Due to the sudden outbreak of COVID-19 at the end of 2019, rapid detection has become an urgent need for community clinics and hospitals. The rapid development of isothermal amplification detection technology for nucleic acids in the field of molecular diagnostic point-of-care testing (POCT) has gained a great deal of attention in recent years. Thanks to intensive research on nicking enzymes, nicking enzyme-combined isothermal amplification has become a promising platform for rapid detection. This is a novel technique that uses nicking enzymes to improve ordinary isothermal amplification. It has garnered significant interest as it overcomes the complexity of traditional molecular diagnostics and is not subject to temperature limitations, relying on cleavage enzymes to efficiently amplify targets in a very short time to provide a high level of amplification efficiency. In recent years, several types of nicking enzyme-combined isothermal amplification have been developed and they have shown great potential in molecular diagnosis, immunodiagnosis, biochemical identification, and other fields. However, this kind of amplification has some disadvantages. In this review, the principles, advantages and disadvantages, and applications of several nicking enzyme-combined isothermal amplification techniques are reviewed and the prospects for the development of these techniques are also considered.
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Affiliation(s)
- Siyu Cao
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China;
| | - Xiaochen Tang
- Department of Clinical Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China;
| | - Tianshu Chen
- Department of Clinical Laboratory Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China;
- Correspondence: (T.C.); (G.C.)
| | - Guifang Chen
- Center for Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, China;
- Correspondence: (T.C.); (G.C.)
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Doroszkiewicz J, Groblewska M, Mroczko B. Molecular Biomarkers and Their Implications for the Early Diagnosis of Selected Neurodegenerative Diseases. Int J Mol Sci 2022; 23:ijms23094610. [PMID: 35563001 PMCID: PMC9100918 DOI: 10.3390/ijms23094610] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/15/2022] [Accepted: 04/20/2022] [Indexed: 02/07/2023] Open
Abstract
The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs—i.e., Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)—as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.
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Affiliation(s)
- Julia Doroszkiewicz
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland;
- Correspondence: ; Tel.: +48-85-686-51-68
| | - Magdalena Groblewska
- Department of Biochemical Diagnostics, University Hospital in Białystok, 15-269 Bialystok, Poland;
| | - Barbara Mroczko
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland;
- Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
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35
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miRNAs in Cancer (Review of Literature). Int J Mol Sci 2022; 23:ijms23052805. [PMID: 35269947 PMCID: PMC8910953 DOI: 10.3390/ijms23052805] [Citation(s) in RCA: 135] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 02/27/2022] [Accepted: 03/02/2022] [Indexed: 02/07/2023] Open
Abstract
MicroRNAs (miRNAs) are short, noncoding, single-stranded RNA molecules that regulate gene expression at the post-transcriptional level by binding to mRNAs. miRNAs affect the course of processes of fundamental importance for the proper functioning of the organism. These processes include cell division, proliferation, differentiation, cell apoptosis and the formation of blood vessels. Altered expression of individual miRNAs has been shown in numerous cancers, which may indicate the oncogenic or suppressor potential of the molecules in question. This paper discusses the current knowledge about the possibility of using miRNA as a diagnostic marker and a potential target in modern anticancer therapies.
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Sousa DA, Carneiro M, Ferreira D, Moreira FTC, Sales MGFV, Rodrigues LR. Recent advances in the selection of cancer-specific aptamers for the development of biosensors. Curr Med Chem 2022; 29:5850-5880. [PMID: 35209816 DOI: 10.2174/0929867329666220224155037] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 11/30/2021] [Accepted: 12/19/2021] [Indexed: 11/22/2022]
Abstract
An early diagnosis has the potential to greatly decrease cancer mortality. For that purpose, specific cancer biomarkers have been molecularly targeted by aptamer sequences to enable an accurate and rapid detection. Aptamer-based biosensors for cancer diagnostics are a promising alternative to those using antibodies, due to their high affinity and specificity to the target molecules and advantageous production. Synthetic nucleic acid aptamers are generated by in vitro Systematic Evolution of Ligands by Exponential enrichment (SELEX) methodologies that have been improved over the years to enhance the efficacy and to shorten the selection process. Aptamers have been successfully applied in electrochemical, optical, photoelectrochemical and piezoelectrical-based detection strategies. These aptasensors comprise a sensitive, accurate and inexpensive option for cancer detection being used as point-of-care devices. This review highlights the recent advances in cancer biomarkers, achievements and optimizations made in aptamer selection, as well as the different aptasensors developed for the detection of several cancer biomarkers.
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Affiliation(s)
- Diana A Sousa
- CEB- Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- MIT-Portugal Program, Lisbon, Portugal
| | - Mariana Carneiro
- CEB- Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- BioMark@ISEP, School of Engineering, Polytechnic of Porto, Porto, Portugal
| | - Débora Ferreira
- CEB- Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- MIT-Portugal Program, Lisbon, Portugal
| | - Felismina T C Moreira
- CEB- Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- BioMark@ISEP, School of Engineering, Polytechnic of Porto, Porto, Portugal
| | - Maria Goreti F V Sales
- CEB- Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- MIT-Portugal Program, Lisbon, Portugal
- BioMark@UC, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal
| | - Lígia R Rodrigues
- CEB- Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
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Szudy-Szczyrek A, Mlak R, Mielnik M, Mazurek M, Chocholska S, Podgajna M, Szczyrek M, Homa-Mlak I, Małecka-Massalska T, Hus M. Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma. Cells 2022; 11:cells11040752. [PMID: 35203396 PMCID: PMC8870602 DOI: 10.3390/cells11040752] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023] Open
Abstract
MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16–3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie–Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high β2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20–7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.
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Affiliation(s)
- Aneta Szudy-Szczyrek
- Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.); (S.C.); (M.P.)
- Correspondence: (A.S.-S.); (M.H.)
| | - Radosław Mlak
- Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (R.M.); (M.M.); (I.H.-M.); (T.M.-M.)
| | - Michał Mielnik
- Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.); (S.C.); (M.P.)
| | - Marcin Mazurek
- Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (R.M.); (M.M.); (I.H.-M.); (T.M.-M.)
| | - Sylwia Chocholska
- Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.); (S.C.); (M.P.)
| | - Martyna Podgajna
- Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.); (S.C.); (M.P.)
| | - Michał Szczyrek
- Chair and Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Iwona Homa-Mlak
- Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (R.M.); (M.M.); (I.H.-M.); (T.M.-M.)
| | - Teresa Małecka-Massalska
- Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland; (R.M.); (M.M.); (I.H.-M.); (T.M.-M.)
| | - Marek Hus
- Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland; (M.M.); (S.C.); (M.P.)
- Correspondence: (A.S.-S.); (M.H.)
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Krämer J, Kang R, Grimm LM, De Cola L, Picchetti P, Biedermann F. Molecular Probes, Chemosensors, and Nanosensors for Optical Detection of Biorelevant Molecules and Ions in Aqueous Media and Biofluids. Chem Rev 2022; 122:3459-3636. [PMID: 34995461 PMCID: PMC8832467 DOI: 10.1021/acs.chemrev.1c00746] [Citation(s) in RCA: 162] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Indexed: 02/08/2023]
Abstract
Synthetic molecular probes, chemosensors, and nanosensors used in combination with innovative assay protocols hold great potential for the development of robust, low-cost, and fast-responding sensors that are applicable in biofluids (urine, blood, and saliva). Particularly, the development of sensors for metabolites, neurotransmitters, drugs, and inorganic ions is highly desirable due to a lack of suitable biosensors. In addition, the monitoring and analysis of metabolic and signaling networks in cells and organisms by optical probes and chemosensors is becoming increasingly important in molecular biology and medicine. Thus, new perspectives for personalized diagnostics, theranostics, and biochemical/medical research will be unlocked when standing limitations of artificial binders and receptors are overcome. In this review, we survey synthetic sensing systems that have promising (future) application potential for the detection of small molecules, cations, and anions in aqueous media and biofluids. Special attention was given to sensing systems that provide a readily measurable optical signal through dynamic covalent chemistry, supramolecular host-guest interactions, or nanoparticles featuring plasmonic effects. This review shall also enable the reader to evaluate the current performance of molecular probes, chemosensors, and nanosensors in terms of sensitivity and selectivity with respect to practical requirement, and thereby inspiring new ideas for the development of further advanced systems.
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Affiliation(s)
- Joana Krämer
- Institute
of Nanotechnology, Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
| | - Rui Kang
- Institute
of Nanotechnology, Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
| | - Laura M. Grimm
- Institute
of Nanotechnology, Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
| | - Luisa De Cola
- Institute
of Nanotechnology, Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
- Dipartimento
DISFARM, University of Milano, via Camillo Golgi 19, 20133 Milano, Italy
- Department
of Molecular Biochemistry and Pharmacology, Instituto di Ricerche Farmacologiche Mario Negri, IRCCS, 20156 Milano, Italy
| | - Pierre Picchetti
- Institute
of Nanotechnology, Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
| | - Frank Biedermann
- Institute
of Nanotechnology, Karlsruhe Institute of
Technology (KIT), Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
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Toden S, Goel A. Non-coding RNAs as liquid biopsy biomarkers in cancer. Br J Cancer 2022; 126:351-360. [PMID: 35013579 PMCID: PMC8810986 DOI: 10.1038/s41416-021-01672-8] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 11/17/2021] [Accepted: 12/07/2021] [Indexed: 01/12/2023] Open
Abstract
Although non-coding RNAs have long been considered as non-functional "junk" RNAs, accumulating evidence in the past decade indicates that they play a critical role in pathogenesis of various cancers. In addition to their biological significance, the recognition that their expression levels are frequently dysregulated in multiple cancers have fueled the interest for exploiting their clinical potential as cancer biomarkers. In particular, microRNAs (miRNAs), a subclass of small non-coding RNAs that epigenetically modulate gene-transcription, have become one of the most well-studied substrates for the development of liquid biopsy biomarkers for cancer patients. The emergence of high-throughput sequencing technologies has enabled comprehensive molecular characterisation of various non-coding RNA expression profiles in multiple cancers. Furthermore, technological advances for quantifying lowly expressed RNAs in the circulation have facilitated robust identification of previously unrecognised and undetectable biomarkers in cancer patients. Here we summarise the latest progress on the utilisation of non-coding RNAs as non-invasive cancer biomarkers. We evaluated the suitability of multiple non-coding RNA types as blood-based cancer biomarkers and examined the impact of recent technological breakthroughs on the development of non-invasive molecular biomarkers in cancer.
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Affiliation(s)
- Shusuke Toden
- Molecular Stethoscope Inc., South San Francisco, CA 94080 USA
| | - Ajay Goel
- grid.410425.60000 0004 0421 8357Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA 91016 USA ,grid.410425.60000 0004 0421 8357City of Hope Comprehensive Cancer Center, Duarte, CA 91010 USA
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40
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Osan C, Chira S, Nutu AM, Braicu C, Baciut M, Korban SS, Berindan-Neagoe I. The Connection between MicroRNAs and Oral Cancer Pathogenesis: Emerging Biomarkers in Oral Cancer Management. Genes (Basel) 2021; 12:genes12121989. [PMID: 34946938 PMCID: PMC8700798 DOI: 10.3390/genes12121989] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 02/06/2023] Open
Abstract
Oral cancer is a common human malignancy that still maintains an elevated mortality rate despite scientific progress. Tumorigenesis is driven by altered gene expression patterns of proto-oncogenes and tumor-suppressor genes. MicroRNAs, a class of short non-coding RNAs involved in gene regulation, seem to play important roles in oral cancer development, progression, and tumor microenvironment modulation. As properties of microRNAs render them stable in diverse liquid biopsies, together with their differential expression signature in cancer cells, these features place microRNAs at the top of promising biomarkers for diagnostic and prognostic values. In this review, we highlight eight expression levels and functions of the most relevant microRNAs involved in oral cancer development, progression, and microenvironment sustainability. Furthermore, we emphasize the potential of using these small RNA species as non-invasive biomarkers for the early detection of oral cancerous lesions. Conclusively, we highlight the perspectives and limitations of microRNAs as novel diagnostic tools, as well as therapeutic models.
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Affiliation(s)
- Ciprian Osan
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Sergiu Chira
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Andreea Mihaela Nutu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
| | - Mihaela Baciut
- Department of Maxillofacial Surgery and Implantology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400033 Cluj-Napoca, Romania;
| | - Schuyler S. Korban
- Department of Natural Resources & Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;
| | - Ioana Berindan-Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (C.O.); (S.C.); (A.M.N.); (C.B.)
- Correspondence:
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Kalhori MR, Soleimani M, Arefian E, Alizadeh AM, Mansouri K, Echeverria J. The potential role of miR-1290 in cancer progression, diagnosis, prognosis, and treatment: An oncomiR or onco-suppressor microRNA? J Cell Biochem 2021; 123:506-531. [PMID: 34897783 DOI: 10.1002/jcb.30191] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 07/20/2021] [Accepted: 11/24/2021] [Indexed: 12/11/2022]
Abstract
Cancer is one of the leading causes of death in humans because of the lack of early diagnosis, distant metastases, and the resistance to adjuvant therapies, including chemotherapy and radiotherapy. In addition to playing an essential role in tumor progression and development, microRNAs (miRNAs) can be used as a robust biomarker in the early detection of cancer. MiR-1290 was discovered for the first time in human embryonic stem cells, and under typical physiological situations, plays an essential role in neuronal differentiation and neural stem cell proliferation. Its coding sequence is located at the 1p36.13 regions in the first intron of the aldehyde dehydrogenase 4 gene member A1. miR-1290 is out of control in many cancers such as breast cancer, colorectal cancer, esophageal squamous cell carcinoma, gastric cancer, lung cancer, pancreatic cancer, and plays a vital role in their development. Therefore, it is suggested that miR-1290 can be considered as a potential diagnostic and therapeutic target in many cancers. In addition to the importance of miR-1290 in the noninvasive diagnosis of various cancers, this systematic review study discussed the role of miR-1290 in altering the expression of different genes involved in cancer development and chemo-radiation resistance. Moreover, it considered the regulatory effect of natural products on miR-1290 expression and the interaction of lncRNAs by miR-1290.
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Affiliation(s)
- Mohammad Reza Kalhori
- Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Masoud Soleimani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ehsan Arefian
- Department of Microbiology, Molecular Virology Lab, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Ali Mohammad Alizadeh
- Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Kamran Mansouri
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Javier Echeverria
- Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile
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Circulating MicroRNAs in Relation to Esophageal Adenocarcinoma Diagnosis and Survival. Dig Dis Sci 2021; 66:3831-3841. [PMID: 33403483 PMCID: PMC8257775 DOI: 10.1007/s10620-020-06740-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 11/19/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Tissue miRNA can discriminate between esophageal adenocarcinoma (EA) and normal epithelium. However, no studies have examined a comprehensive panel of circulating miRNAs in relation to EA diagnosis and survival. METHODS We used all 62 EA cases from the US Multi-Center case-control study with available serum matched 1:1 to controls. Cases were followed for vital status. MiRNAs (n = 2064) were assessed using the HTG EdgeSeq miRNA Whole Transcriptome Assay. Differential expression analysis of miRNAs in relation to case-control status was conducted. In cases, Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. P values were adjusted using the Benjamini-Hochberg (BH) procedure for false discovery rate control. Predictive performance was assessed using cross-validation. RESULTS Sixty-eight distinct miRNAs were significantly upregulated between cases and controls (e.g., miR-1255b-2-3p fold change = 1.74, BH-adjusted P = 0.01). Assessing the predictive performance of these significantly upregulated miRNAs yielded 60% sensitivity, 65% specificity, and 0.62 AUC. miR-4253 and miR-1238-5p were associated with risk of mortality after EA diagnosis (HR = 4.85, 95% CI: 2.30-10.23, BH-adjusted P = 0.04 and HR = 3.81, 95% CI: 2.02-7.19, BH-adjusted P = 0.04, respectively). CONCLUSIONS While they require replication, these findings suggest that circulating miRNAs may be associated with EA diagnosis and survival.
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Hu J, Stojanović J, Yasamineh S, Yasamineh P, Karuppannan SK, Hussain Dowlath MJ, Serati-Nouri H. The potential use of microRNAs as a therapeutic strategy for SARS-CoV-2 infection. Arch Virol 2021; 166:2649-2672. [PMID: 34278528 PMCID: PMC8286877 DOI: 10.1007/s00705-021-05152-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 03/21/2021] [Indexed: 02/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there is no effective therapeutic approach for treating SARS-CoV-2 infections. MicroRNAs (miRNAs) have been recognized to target the viral genome directly or indirectly, thereby inhibiting viral replication. Several studies have demonstrated that host miRNAs target different sites in SARS-CoV-2 RNA and constrain the production of essential viral proteins. Furthermore, miRNAs have lower toxicity, are more immunogenic, and are more diverse than protein-based and even plasmid-DNA-based therapeutic agents. In this review, we emphasize the role of miRNAs in viral infection and their potential use as therapeutic agents against COVID-19 disease. The potential of novel miRNA delivery strategies, especially EDV™ nanocells, for targeting lung tissue for treatment of SARS-CoV-2 infection is also discussed.
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Affiliation(s)
- Jiulue Hu
- Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, 473004, Henan, China
| | - Jelena Stojanović
- Faculty of Mathematics and Computer Science in Belgrade, ALFA BK University, Belgrade, Serbia
| | - Saman Yasamineh
- Young Researcher and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
| | - Pooneh Yasamineh
- Young Researcher and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Sathish Kumar Karuppannan
- Center for Environmental Nuclear Research, Directorate of Research and Virtual Education, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603203, Kanchipuram, Chennai, Tamil Nadu, India
| | - Mohammed Junaid Hussain Dowlath
- Center for Environmental Nuclear Research, Directorate of Research and Virtual Education, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, 603203, Kanchipuram, Chennai, Tamil Nadu, India
| | - Hamed Serati-Nouri
- Stem cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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High allele discrimination in the typing of single nucleotide polymorphisms of miRNA. Bioorg Med Chem 2021; 46:116363. [PMID: 34419822 DOI: 10.1016/j.bmc.2021.116363] [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: 07/18/2021] [Revised: 08/05/2021] [Accepted: 08/07/2021] [Indexed: 11/22/2022]
Abstract
MicroRNAs (miRNAs) belonging to the same family have similar sequences and are difficult to identify. Herein, we report the reverse transcription-hairpin-probe-polymerase chain reaction (RT-Hpro-PCR) technique, which utilises a reverse transcription (RT) primer containing a 5'-end deoxyribonucleic acid (DNA) tag, to detect miRNAs with similar sequences. This strategy follows a two-step RT-PCR method using 6-7-mer RT-primers with a ~ 10-mer tag sequence at the 5'-end and a probe with a hairpin structure (Hpro), including two C-bulges, attached. The findings demonstrate that the specificity of RT could be increased by shortening the complementary part of the RT primer containing a different base, wherein the PCR could successfully progress with the use of 5'-end DNA tag because of an increase in the length of the hybridised tagged primer. This study shows the potential of RT-Hpro-PCR to precisely detect miRNAs with similar sequences, which could help explore the roles of miRNAs in several biological processes.
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A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma. Cancers (Basel) 2021; 13:cancers13153877. [PMID: 34359778 PMCID: PMC8345491 DOI: 10.3390/cancers13153877] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/24/2021] [Accepted: 07/26/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Multiple myeloma bone disease (MMBD) is one of the most important complications of multiple myeloma with a great impact on quality of life. Recent advances in the field of imaging techniques provided clinicians with a variety of imaging modalities with high sensitivity for the diagnosis of MMBD. However, no circulating biomarkers are available to support the diagnosis of MMBD in cases where the results are inconclusive. The aim of our study was to investigate the clinical utility of 19 miRNAs implicated in osteoporosis in MMBD. Our results suggest that the levels of circulating let-7b-5p, miR-143-3p, miR-17-5p, miR-335-5p, and miR-214-3p (standalone or combined in multi-miRNA models) can effectively predict the presence of MMBD in newly diagnosed MM patients. Abstract Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA–based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM.
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Circulating non-coding RNAs as new biomarkers and novel therapeutic targets in colorectal cancer. Clin Transl Oncol 2021; 23:2220-2236. [PMID: 34275108 DOI: 10.1007/s12094-021-02639-0] [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: 10/14/2020] [Accepted: 05/06/2021] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors, and a large number of patients are diagnosed and die every year. Due to the lack of appropriate diagnosis, prediction and treatment, early diagnosis rate of CRC is low and the prognosis is poor. Studies have found that abnormally expressed non-coding RNAs (ncRNAs) (including microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs),etc.) play an important regulatory role in the occurrence and development of CRC. Some studies have shown that they are stable in the blood and can be detected repeatedly. They are expected to be non-invasive biomarkers for early diagnosis, prognosis evaluation, and prediction of drug sensitivity of CRC, as well as potential applications in the treatment of CRC.
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Torii C, Maishi N, Kawamoto T, Morimoto M, Akiyama K, Yoshioka Y, Minami T, Tsumita T, Alam MT, Ochiya T, Hida Y, Hida K. miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells. Sci Rep 2021; 11:13502. [PMID: 34226586 PMCID: PMC8257582 DOI: 10.1038/s41598-021-92879-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Tumor endothelial cells (TECs) reportedly exhibit altered phenotypes. We have demonstrated that TECs acquire drug resistance with the upregulation of P-glycoprotein (P-gp, ABCB1), contrary to traditional assumptions. Furthermore, P-gp expression was higher in TECs of highly metastatic tumors than in those of low metastatic tumors. However, the detailed mechanism of differential P-gp expression in TECs remains unclear. miRNA was identified in highly metastatic tumor extracellular vesicles (EVs) and the roles of miRNA in endothelial cell resistance were analyzed in vitro and in vivo. In the present study, we found that treatment of highly metastatic tumor-conditioned medium induced resistance to 5-fluorouracil (5-FU) with interleukin-6 (IL-6) upregulation in endothelial cells (ECs). Among the soluble factors secreted from highly metastatic tumors, we focused on EVs and determined that miR-1246 was contained at a higher level in highly metastatic tumor EVs than in low metastatic tumor EVs. Furthermore, miR-1246 was transported via the EVs into ECs and induced IL-6 expression. Upregulated IL-6 induced resistance to 5-FU with STAT3 and Akt activation in ECs in an autocrine manner. These results suggested that highly metastatic tumors induce drug resistance in ECs by transporting miR-1246 through EVs.
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Affiliation(s)
- Chisaho Torii
- Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
- Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan
- Department of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Nako Maishi
- Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
- Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan
- Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Taisuke Kawamoto
- Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Masahiro Morimoto
- Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan
- Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
- Department of Oral Diagnosis and Medicine, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Kosuke Akiyama
- Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Yusuke Yoshioka
- Institute of Medical Science, Tokyo Medical University, Tokyo, 160-0023, Japan
| | - Takashi Minami
- Division of Molecular and Vascular Biology, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, 860-0811, Japan
| | - Takuya Tsumita
- Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Mohammad Towfik Alam
- Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
- Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan
- Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan
| | - Takahiro Ochiya
- Institute of Medical Science, Tokyo Medical University, Tokyo, 160-0023, Japan
| | - Yasuhiro Hida
- Department of Cardiovascular and Thoracic Surgery, Hokkaido University Faculty of Medicine, Sapporo, 060-8638, Japan
| | - Kyoko Hida
- Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan.
- Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan.
- Department of Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan.
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Diving into the Pleural Fluid: Liquid Biopsy for Metastatic Malignant Pleural Effusions. Cancers (Basel) 2021; 13:cancers13112798. [PMID: 34199799 PMCID: PMC8200094 DOI: 10.3390/cancers13112798] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/03/2021] [Accepted: 06/03/2021] [Indexed: 12/18/2022] Open
Abstract
Simple Summary Malignant pleural effusion is a common complication arising as the natural progression of many tumors, such as lung cancer. When this occurs, the common protocol consists of analyzing the pleural fluid for the presence of malignant cells. However, on many occasions no malignant cells are found despite a clear suspicion of cancer. Thus, the current diagnostic methodology is imperfect and more precise methods for the identification of malignancy are needed. Nonetheless, these methods are often invasive, which may be counterproductive, especially for patients with poor health condition. These concerns have made clinicians consider alternative non-invasive strategies to diagnose cancer using the generally abundant pleural fluid (e.g., liquid biopsy). Thus, a liquid sample can be analyzed for the presence of cancer footprints, such as circulating malignant cells and tumor nucleic acids. Herein, we review the literature for studies considering pleural fluid as a successful source of liquid biopsy. Abstract Liquid biopsy is emerging as a promising non-invasive diagnostic tool for malignant pleural effusions (MPE) due to the low sensitivity of conventional pleural fluid (PF) cytological examination and the difficulty to obtain tissue biopsies, which are invasive and require procedural skills. Currently, liquid biopsy is increasingly being used for the detection of driver mutations in circulating tumor DNA (ctDNA) from plasma specimens to guide therapeutic interventions. Notably, malignant PF are richer than plasma in tumor-derived products with potential clinical usefulness, such as ctDNA, micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), and circulating tumor cells (CTC). Tumor-educated cell types, such as platelets and macrophages, have also been added to this diagnostic armamentarium. Herein, we will present an overview of the role of the preceding biomarkers, collectively known as liquid biopsy, in PF samples, as well as the main technical approaches used for their detection and quantitation, including a proper sample processing. Technical limitations of current platforms and future perspectives in the field will also be addressed. Using PF as liquid biopsy shows promise for use in current practice to facilitate the diagnosis and management of metastatic MPE.
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Han L, Sun Y, Lu C, Ma C, Shi J, Sun D. MiR-3614-5p Is a Potential Novel Biomarker for Colorectal Cancer. Front Genet 2021; 12:666833. [PMID: 34127929 PMCID: PMC8195682 DOI: 10.3389/fgene.2021.666833] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 05/04/2021] [Indexed: 11/13/2022] Open
Abstract
MiR-3614-5p has been found in a variety of cancers including colorectal cancer. However, the association of miR-3614-5p with colorectal cancer is still unclear. Based on the Cancer Genome Atlas (TCGA) database, the relationship between miR-3614-5p and colorectal cancer can be proved. Wilcoxon rank-sum test was used to compare the miR-3614-5p expression in colorectal cancer tissues and under normal conditions, respectively. The logistic regression method was further employed to analyze the relationship between miR-3614-5p and clinicopathological characteristics. Also, the correlation between miR-3614-5p and survival rate was evaluated by Kaplan-Meier and Cox regression analysis. Besides, gene set enrichment analysis (GSEA) was used to investigate the biological functions of miR-3614-5p. The decrease of miR-3614-5p expression of colorectal cancer was significantly correlated with N stage (OR) = 0.7 for N1&N2 vs. N0), M stage (OR = 0.5 for M1 vs. M0), pathologic stage (OR = 0.7 for Stage III & Stage IV vs. Stage I & Stage II), neoplasm type (OR = 0.5 for rectum adenocarcinoma vs. colon adenocarcinoma), and lymphatic invasion (OR = 0.6 for YES vs. NO) (all p-values < 0.05). Kaplan-Meier survival analysis showed that colorectal cancer with low miR-3614-5p has a poorer prognosis than that of high miR-3614-5p (p = 0.005). According to univariate analysis, low miR-3614-5p was associated with poor overall survival (OS) [hazard ratio (HR) = 0.599; 95% confidence interval (CI): 0.418-0.857; p = 0.005]. In multivariate analysis, miR-3614-5p was closely related to OS (HR = 0.630; 95% CI: 0.405-0.978, p = 0.021). GSEA showed that the high expression phenotype of miR-3614-5p differentially enriches the P53 pathway. Meanwhile, the high expression phenotype of miR-3614-5p enhanced NK T cell activation, negative T cell selection, response to interleukin 2, and response to tumor cells. MiR-3614-5p is a possible prognostic marker of low survival rate for patients with colorectal cancer. Moreover, the P53 pathway and P38MAPK pathway may be the key pathways regulated by miR-3614-5p in colorectal cancer.
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Affiliation(s)
- Lin Han
- Graduate School, Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Yanjun Sun
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
| | - Cansheng Lu
- Department of Anus and Colon Surgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Chungeng Ma
- Department of Anus and Colon Surgery, The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Jian Shi
- Department of Anus and Colon Surgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China
| | - Dengqun Sun
- Department of General Surgery, The Armed Police Corps Hospital of Anhui, Hefei, China
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Ma L, Wu D. MicroRNA-383-5p regulates osteogenic differentiation of human periodontal ligament stem cells by targeting histone deacetylase 9. Arch Oral Biol 2021; 129:105166. [PMID: 34118749 DOI: 10.1016/j.archoralbio.2021.105166] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/17/2021] [Accepted: 05/20/2021] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Human periodontal ligament stem cells (hPDLSCs) play an important role in regenerative engineering technology for periodontal therapy. The mechanism of microRNA (miR)-383-5p in osteogenic differentiation needs further exploration. This study aimed at investigating the potential role of miR-383-5p in the osteogenic differentiation of hPDLSCs. METHODS Osteogenic differentiation of hPDLSCs was induced by osteoblastinducing media and evaluated by Alizarin Red staining and Alkaline phosphatase staining. To examine the role of miR-383-5p in osteogenic differentiation, miR-383-5p mimic or inhibitor and histone deacetylase (HDAC) 9 overexpression plasmid or siRNA-HDAC9 were co-transfected into hPDLSCs. qRT-PCR and Western blot were applied for detection of mRNA and protein levels. RESULTS During the osteogenic differentiation of hPDLSCs, miR-383-5p expression was gradually up-regulated, while HDAC9 mRNA level was down-regulated. HDAC9 overexpression suppressed Alkaline phosphatase activity, mineral node formation and the expressions of osteogenic markers including Runx family transcription factor 2 (RUNX2), osteocalcin and Smad family member 4 (Smad4) in the differentiated hPDLSCs, while siHDAC9 exerted opposite effects on osteogenic differentiation. The Alkaline phosphatase activity, mineral node formation and the expressions of RUNX2, osteocalcin and Smad4 of the differentiated hPDLSCs were regulated by miR-383-5p/HDAC9 axis. The miR-383-5p/HDAC9 axis effectively regulated the expressions of osteogenic markers during the differentiation of hPDLSCs. CONCLUSION MiR-383-5p overexpression facilitated the osteogenic differentiation of hPDLSCs via inhibiting HDAC9 expression.
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Affiliation(s)
- Lan Ma
- Department of Stomatology, Jingmen No.1 People's Hospital, China
| | - Di Wu
- Department of Stomatology, Jingmen No.1 People's Hospital, China.
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