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Alizadeh M, Ghasemi H, Bazhan D, Mohammadi Bolbanabad N, Rahdan F, Arianfar N, Vahedi F, Khatami SH, Taheri-Anganeh M, Aiiashi S, Armand N. MicroRNAs in disease States. Clin Chim Acta 2025; 569:120187. [PMID: 39938625 DOI: 10.1016/j.cca.2025.120187] [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: 11/24/2024] [Revised: 02/08/2025] [Accepted: 02/08/2025] [Indexed: 02/14/2025]
Abstract
This review highlights the role of miRNAs in various diseases affecting major organ systems. miRNAs are small, non-coding RNA molecules that regulate numerous genes. Dysregulation of miRNAs is linked to many pathological conditions due to their involvement in gene silencing and cellular pathways. We discuss miRNA expression patterns, their physiological and pathological roles, and how changes in miRNA levels contribute to disease. Notably, miRNAs like miR-499 and miR-21 are implicated in heart failure and atherosclerosis. miRNA dysregulation is also associated with colorectal and gastric cancers, influencing tumorigenesis and chemoresistance. In neurological diseases, miRNAs exhibit diverse profiles that affect neurodevelopment and degeneration. Additionally, miRNAs modulate cell function in reproductive organs, impacting fertility and cancer progression. miRNAs such as miR-192 and miR-204 serve as biomarkers for nephropathy and acute kidney injury. These miRNAs are involved in skeletal muscle diseases, contributing to conditions like osteoporosis and sarcopenia. miRNAs function as oncogenes or tumor suppressors in cancer, highlighting their potential in diagnostics and therapy. Further research is needed to develop miRNA-based diagnostics and treatments.
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Affiliation(s)
- Mehdi Alizadeh
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Ghasemi
- Research Center for Environmental Contaminants (RCEC), Abadan University of Medical Sciences, Abadan, Iran
| | - Donya Bazhan
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Fereshteh Rahdan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Narges Arianfar
- Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzaneh Vahedi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Seyyed Hossein Khatami
- Student Research Committee, Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Saleh Aiiashi
- Abadan University of Medical Sciences, Abadan, Iran.
| | - Nezam Armand
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.
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Sun Y, Peng Y, Sun Y, Xu D. An enzyme-free and label-free multiplex detection of miRNAs by entropy-driven circuit coupled with capillary electrophoresis. Talanta 2025; 281:126850. [PMID: 39276573 DOI: 10.1016/j.talanta.2024.126850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 08/23/2024] [Accepted: 09/07/2024] [Indexed: 09/17/2024]
Abstract
MicroRNAs (miRNAs) are currently recognized as important biomarkers for the early diagnosis and prognostic treatment of cancer. Herein, we developed a simple and label-free method for the multiplex detection of miRNAs, based on entropy-driven circuit (EDC) amplification and non-gel sieving capillary electrophoresis-LED induced fluorescence detection (NGCE-LEDIF) platform. In this system, three different lengths of fuel chains were designed to catalyze three EDC, targeting miRNA-21, miRNA-155, and miRNA-10b, respectively. In the presence of target miRNA, the EDC cycle amplification reaction was triggered, generating numerous stable double-strands products (F-DNA/L-DNA). Since the three miRNAs correspond to three different lengths of F-DNA/L-DNA, they can be easily isolated and detected by NGCE. This strategy has good sensitivity, with detection limits of 68 amol, 292.2 amol, and 394 amol for miRNA-21, miRNA-155, and miRNA-10b, respectively. Additionally, this method has good specificity and can effectively distinguish single-base mismatches of miRNA. The recoveries of the three miRNAs in deproteinized healthy human serum ranged from 91.28 % to 108.4 %, with a relative standard deviation (RSD) of less than 7.9 %. This method was further applied to detect cellular miRNAs in human breast cancer (MCF-7) cell extracts, revealing an up-regulation of miRNA-21, miRNA-155, and miRNA-10b in MCF-7 cells. The successful spiked recovery in human serum and RNA extraction from MCF-7 cells underscores the practicality of this method. Therefore, this strategy has broad application prospects in biomedical research.
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Affiliation(s)
- Yanyan Sun
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, No 163, Xianlin Avenue, Nanjing, 210023, PR China
| | - Yufei Peng
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, No 163, Xianlin Avenue, Nanjing, 210023, PR China
| | - Yunlong Sun
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, No 163, Xianlin Avenue, Nanjing, 210023, PR China
| | - Danke Xu
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, No 163, Xianlin Avenue, Nanjing, 210023, PR China.
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Yuan P, Gao X, Xu M, Qiu L, Xiong Z, Shen J, Xing H, Yang R, Zhao L, Liu X, Gu J, Liu W. Novel miRNA markers and their mechanism of esophageal squamous cell carcinoma (ESCC) based on TCGA. Sci Rep 2024; 14:27261. [PMID: 39516222 PMCID: PMC11549395 DOI: 10.1038/s41598-024-76321-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 10/14/2024] [Indexed: 11/16/2024] Open
Abstract
MicroRNAs(miRNAs) are promising biomarkers for early esophageal squamous cell carcinoma (ESCC) detection and prognostic prediction. This study aimed to explore the potential biomarkers and molecular pathogenesis in the early diagnosis of ESCC. Firstly, 48 differentially expressed miRNAs (DEMs) and 1319 differentially expressed genes (DEGs) were identified between 94 ESCC tissues and 13 normal esophageal tissues in TCGA. From miRNA-mRNA regulatory network, there are 6558 target genes of the 48 DEMs, where 400 target genes are also among 1319 DEGs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment indicate that the 400 DEGs significantly enriched in cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and oocyte meiosis. And there are 66 DEGs among these six biological pathways, which we called GO-DEGs. From miRNA-mRNA regulatory network, 32 DEMs regulated the 66 GO-DEGs, where 22 DEMs were verified by different types of experiments in ESCC tissues, cells, or serum from the literature. For the other novel 10 DEMs, single-factor Cox regression analysis show that only hsa-miR-34b-3p showed no significant correlation with the overall survival of ESCC patients. Finally, we obtained the novel 9 ESCC-related DEMs, where three are down-regulated, and six are up-regulated. We analyzed the expression trends of target genes for five miRNAs and identified three significantly different miRNAs (hsa-miR-205-3p, hsa-miR-452-3p, and hsa-miR-6499-3p) confirmed by qPCR. Moreover, the stage-specific miRNAs were also suggested. These three qPCR validated miRNAs are also specific to the early stages of ESCC: hsa-miR-452-3p is specific to Stage I, II and III; hsa-miR-205-3p is specific in Stage II and III; and hsa-miR-6499-3p is Stage II specific. They might be the potential biomarkers for ESCC stage diagnosis. This study identified three novel miRNA markers potentially related to the diagnosis of ESCC and participated in the occurrence and development of ESCC through cell cycle, proteoglycans in cancer, p53 signaling pathway, protein digestion and absorption, transcriptional dysregulation in cancer, and signaling pathway for oocyte meiosis.
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Affiliation(s)
- Ping Yuan
- Healthcare Big Data Center, School of Public Health, Hubei University of Medicine, 30 Chaoyang Middle Road, Shiyan, 442000, Hubei, People's Republic of China
- Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Xiaoyan Gao
- Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Mingjun Xu
- Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Liangyu Qiu
- Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Zijun Xiong
- Healthcare Big Data Center, School of Public Health, Hubei University of Medicine, 30 Chaoyang Middle Road, Shiyan, 442000, Hubei, People's Republic of China
| | - Jun Shen
- Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China
- Xinjiang Key Laboratory of Cardiac Electrophysiology and Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Huanhuan Xing
- Healthcare Big Data Center, School of Public Health, Hubei University of Medicine, 30 Chaoyang Middle Road, Shiyan, 442000, Hubei, People's Republic of China
| | - Ruofan Yang
- Healthcare Big Data Center, School of Public Health, Hubei University of Medicine, 30 Chaoyang Middle Road, Shiyan, 442000, Hubei, People's Republic of China
| | - Liang Zhao
- Precision Medicine Research Center, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Xi Liu
- Healthcare Big Data Center, School of Public Health, Hubei University of Medicine, 30 Chaoyang Middle Road, Shiyan, 442000, Hubei, People's Republic of China
| | - Jiaowei Gu
- Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
- Department of Pediatrics, Taihe Hospital, Hubei University of Medicine, 32 Renmin South Road, Shiyan, 442000, Hubei, People's Republic of China.
| | - Wenting Liu
- Healthcare Big Data Center, School of Public Health, Hubei University of Medicine, 30 Chaoyang Middle Road, Shiyan, 442000, Hubei, People's Republic of China.
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Sharma S, Artner T, Preissner KT, Lang IM. Nucleic acid liquid biopsies in cardiovascular disease: Cell-free RNA liquid biopsies in cardiovascular disease. Atherosclerosis 2024; 398:118584. [PMID: 39306538 DOI: 10.1016/j.atherosclerosis.2024.118584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 08/15/2024] [Accepted: 08/29/2024] [Indexed: 11/17/2024]
Abstract
Cardiovascular diseases (CVD) and their complications continue to be the leading cause of mortality globally. With recent advancements in molecular analytics, individualized treatments are gradually applied to the diagnosis and treatment of CVD. In the field of diagnostics, liquid biopsy combined with modern analytical technologies is the most popular natural source to identify disease biomarkers, as has been successfully demonstrated in the cancer field. While it is not easy to obtain any diseased tissue for different types of CVD such as atherosclerosis, deep vein thrombosis or stroke, liquid biopsies provide a simple and non-invasive alternative to surgical tissue specimens to obtain dynamic molecular information reflecting disease states. The release of cell-free ribonucleic acids (cfRNA) from stressed/damaged/dying and/or necrotic cells is a common physiological phenomenon. CfRNAs are a heterogeneous population of various types of extracellular RNA found in body fluids (blood, urine, saliva, cerebrospinal fluid) or in association with vascular/atherosclerotic tissue, offering insights into disease pathology on a diagnostic front. In particular, cf-ribosomal RNA has been shown to act as a damaging molecule in several cardio-vascular disease conditions. Moreover, such pathophysiological functions of cfRNA in CVD have been successfully antagonized by the administration of RNases. In this review, we discuss the origin, structure, types, and potential utilization of cfRNA in the diagnosis of CVD. Together with the analysis of established CVD biomarkers, the profiling of cfRNA in body fluids may thereby provide a promising approach for early disease detection and monitoring.
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Affiliation(s)
- Smriti Sharma
- Department of Internal Medicine II, Cardiology, Medical University of Vienna, Vienna, Austria
| | - Tyler Artner
- Department of Internal Medicine II, Cardiology, Medical University of Vienna, Vienna, Austria
| | - Klaus T Preissner
- Kerckhoff-Heart Research Institute, Department Cardiology, Justus-Liebig-University, Giessen, Germany
| | - Irene M Lang
- Department of Internal Medicine II, Cardiology, Medical University of Vienna, Vienna, Austria.
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Li Y, Baumert BO, Stratakis N, Goodrich JA, Wu H, Liu SH, Wang H, Beglarian E, Bartell SM, Eckel SP, Walker D, Valvi D, La Merrill MA, Inge TH, Jenkins T, Ryder JR, Sisley S, Kohli R, Xanthakos SA, Vafeiadi M, Margetaki A, Roumeliotaki T, Aung M, McConnell R, Baccarelli A, Conti D, Chatzi L. Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children. ENVIRONMENTAL RESEARCH 2024; 259:119496. [PMID: 38936497 PMCID: PMC11847561 DOI: 10.1016/j.envres.2024.119496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/21/2024] [Accepted: 06/24/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. OBJECTIVE To investigate associations between PFAS concentrations and miRNA levels in children. METHODS Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. RESULTS Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. CONCLUSION Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.
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Affiliation(s)
- Yijie Li
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Brittney O Baumert
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | - Jesse A Goodrich
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Haotian Wu
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA
| | - Shelley H Liu
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Hongxu Wang
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Emily Beglarian
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Scott M Bartell
- Department of Environmental and Occupational Health and Department of Epidemiology and Biostatistics, University of California, Irvine, CA, USA
| | - Sandrah Proctor Eckel
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Douglas Walker
- Gangarosa Department of Environmental Health, Rollins School of Public Health, 1518 Clifton Road, NE, Atlanta, GA, USA
| | - Damaskini Valvi
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Thomas H Inge
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
| | - Todd Jenkins
- Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
| | - Justin R Ryder
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
| | - Stephanie Sisley
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Rohit Kohli
- Division of Gastroenterology, Children's Hospital Los Angeles, Los Angeles, CA, USA
| | - Stavra A Xanthakos
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Marina Vafeiadi
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Aikaterini Margetaki
- Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece
| | - Theano Roumeliotaki
- Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; Department of Social Medicine, School of Medicine, University of Crete, Greece
| | - Max Aung
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Rob McConnell
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Andrea Baccarelli
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA
| | - David Conti
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Lida Chatzi
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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Na H, Koo BI, Park JC, Lim J, Kim Y, Chung HJ, Nam YS. Live-Cell Imaging of MicroRNA Expression via Photoinduced Electron Transfer Controlled by Catalytic Hairpin Assembly. Adv Healthc Mater 2024; 13:e2401483. [PMID: 38889395 DOI: 10.1002/adhm.202401483] [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: 04/22/2024] [Revised: 06/14/2024] [Indexed: 06/20/2024]
Abstract
MicroRNAs (miRNAs) serve as emerging biomarkers for a range of diseases, and their quantitative analysis draws increasing attention. Yet, current invasive methods limit continuous tracking within living cells. To overcome this, a nonenzymatic DNA-based nanoprobe is developed for dynamic, noninvasive miRNA tracking via live-cell imaging. This probe features a unique hairpin DNA structure with five guanines that act as internal quenchers, suppressing fluorescence from an attached fluorophore via photoinduced electron transfer. Target miRNA initiates toehold-mediated strand displacement, restoring, and amplifying the fluorescence signal. Additionally, by introducing a single mismatch to the hairpin DNA, the nanoprobe's sensitivity is significantly enhanced, lowering the detection limit to about 60 pM without compromising specificity. To optimize intracellular delivery for prolonged monitoring, the nanoprobe is encapsulated within multilamellar lipid nanovesicles, fluorescently labeled for dual-wavelength ratiometric analysis. The proposed nanoprobe demonstrates a significant advance in live-cell miRNA detection, promising enhanced in situ analysis for a better understanding of miRNAs' pathophysiological function.
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Affiliation(s)
- Hyebin Na
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Bon Il Koo
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Jae Chul Park
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Jiwoo Lim
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Yoosik Kim
- Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Hyun Jung Chung
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
| | - Yoon Sung Nam
- Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea
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Lu Z, Wang S, Li P, Yang H, Han S, Zhang S, Ma L. An ultra-sensitive suboptimal protospacer adjacent motif enhanced rolling circle amplification assay based on CRISPR/Cas12a for detection of miR-183. Front Bioeng Biotechnol 2024; 12:1444908. [PMID: 39359259 PMCID: PMC11445046 DOI: 10.3389/fbioe.2024.1444908] [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: 06/06/2024] [Accepted: 09/05/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction MicroRNAs (miRNAs) have been recognized as promising diagnostic biomarkers for Diabetic Retinopathy (DR) due to their notable upregulation in individuals with the condition. However, the development of highly sensitive miRNAs assays for the rapid diagnosis of DR in clinical settings remains a challenging task. Methods In this study, we introduce an enhanced CRISPR/Cas12a assay, leveraging suboptimal PAM (sPAM)-mediated Cas12a trans-cleavage in conjunction with rolling circle amplification (RCA). sPAM was found to perform better than canonical PAM (cPAM) in the detection of Cas12a-mediated ssDNA detection at low concentrations and was used instead of canonical PAM (cPAM) to mediate the detection. The parameters of reactions have also been optimized. Results and discussion In comparison with cPAM, sPAM has higher sensitivity in the detection of ssDNA at concentrations lower than 10 pM by Cas12a. By replacing cPAM with sPAM in the padlock template of RCA, ultra-high sensitivity for miR-183 detection is achieved, with a detection limit of 0.40 aM. within 25 min and a linear range spanning from 1 aM. to 1 pM. Our assay also exhibits exceptional specificity in detecting miR-183 from other miRNAs. Furthermore, the applicability of our assay for the sensitive detection of miR-183 in clinical serum samples is also validated. This study introduces a groundbreaking assay with excellent performance through a simple modification, which not only addresses existing diagnostic challenges, but also opens exciting new avenues for clinical diagnosis in the realm of DR.
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Affiliation(s)
- Zhiquan Lu
- Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua Shenzhen International Graduate School, University Town of Shenzhen, Shenzhen, China
| | - Shijing Wang
- Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, University Town of Shenzhen, Shenzhen, China
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Ping Li
- Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, University Town of Shenzhen, Shenzhen, China
| | - Huasheng Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, China
| | - Sanyang Han
- Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, University Town of Shenzhen, Shenzhen, China
| | - Shaochong Zhang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Lan Ma
- Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua Shenzhen International Graduate School, University Town of Shenzhen, Shenzhen, China
- Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, University Town of Shenzhen, Shenzhen, China
- Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, China
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Aghajani Mir M. Illuminating the pathogenic role of SARS-CoV-2: Insights into competing endogenous RNAs (ceRNAs) regulatory networks. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2024; 122:105613. [PMID: 38844190 DOI: 10.1016/j.meegid.2024.105613] [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: 03/07/2024] [Revised: 05/20/2024] [Accepted: 05/31/2024] [Indexed: 06/10/2024]
Abstract
The appearance of SARS-CoV-2 in 2019 triggered a significant economic and health crisis worldwide, with heterogeneous molecular mechanisms that contribute to its development are not yet fully understood. Although substantial progress has been made in elucidating the mechanisms behind SARS-CoV-2 infection and therapy, it continues to rank among the top three global causes of mortality due to infectious illnesses. Non-coding RNAs (ncRNAs), being integral components across nearly all biological processes, demonstrate effective importance in viral pathogenesis. Regarding viral infections, ncRNAs have demonstrated their ability to modulate host reactions, viral replication, and host-pathogen interactions. However, the complex interactions of different types of ncRNAs in the progression of COVID-19 remains understudied. In recent years, a novel mechanism of post-transcriptional gene regulation known as "competing endogenous RNA (ceRNA)" has been proposed. Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and viral ncRNAs function as ceRNAs, influencing the expression of associated genes by sequestering shared microRNAs. Recent research on SARS-CoV-2 has revealed that disruptions in specific ceRNA regulatory networks (ceRNETs) contribute to the abnormal expression of key infection-related genes and the establishment of distinctive infection characteristics. These findings present new opportunities to delve deeper into the underlying mechanisms of SARS-CoV-2 pathogenesis, offering potential biomarkers and therapeutic targets. This progress paves the way for a more comprehensive understanding of ceRNETs, shedding light on the intricate mechanisms involved. Further exploration of these mechanisms holds promise for enhancing our ability to prevent viral infections and develop effective antiviral treatments.
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Affiliation(s)
- Mahsa Aghajani Mir
- Deputy of Research and Technology, Babol University of Medical Sciences, Babol, Iran.
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9
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Kazlauskiene M, Klimaite R, Kondrotiene A, Dauksa A, Dauksiene D, Verkauskiene R, Zilaitiene B. Plasma miRNA-146b-3p, -222-3p, -221-5p, -21a-3p Expression Levels and TSHR Methylation: Diagnostic Potential and Association with Clinical and Pathological Features in Papillary Thyroid Cancer. Int J Mol Sci 2024; 25:8412. [PMID: 39125979 PMCID: PMC11313006 DOI: 10.3390/ijms25158412] [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: 06/24/2024] [Revised: 07/26/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
This study aimed to investigate the expression of microRNAs (miRNAs) -146b-3p, -221-5p, -222-3p, and -21a-3p and the methylation pattern of the thyroid-stimulating hormone receptor (TSHR) gene in blood plasma samples from papillary thyroid cancer (PTC) patients before and after thyroidectomy compared to healthy controls (HCs). This study included 103 participants, 46 PTC patients and 57 HCs, matched for gender and age. Significantly higher preoperative expression levels of miRNAs and TSHR methylation were determined in the PTC patients compared to HCs. Post-surgery, there was a notable decrease in these biomarkers. Elevated TSHR methylation was linked to larger tumor sizes and lymphovascular invasion, while increased miRNA-222-3p levels correlated with multifocality. Receiver operating characteristic (ROC) analysis showed AUCs below 0.8 for all candidate biomarkers. However, significant changes in the expression of all analyzed miRNAs and TSHR methylation levels indicate their potential to differentiate PTC patients from healthy individuals. These findings suggest that miRNAs and TSHR methylation levels may serve as candidate biomarkers for early diagnosis and monitoring of PTC, with the potential to distinguish PTC patients from healthy individuals. Further research is needed to validate these biomarkers for clinical application.
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Affiliation(s)
- Mintaute Kazlauskiene
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (M.K.); (A.K.); (D.D.); (R.V.); (B.Z.)
| | - Raimonda Klimaite
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (M.K.); (A.K.); (D.D.); (R.V.); (B.Z.)
| | - Aiste Kondrotiene
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (M.K.); (A.K.); (D.D.); (R.V.); (B.Z.)
| | - Albertas Dauksa
- Institute of Digestive Research, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania;
| | - Dalia Dauksiene
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (M.K.); (A.K.); (D.D.); (R.V.); (B.Z.)
| | - Rasa Verkauskiene
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (M.K.); (A.K.); (D.D.); (R.V.); (B.Z.)
| | - Birute Zilaitiene
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania; (M.K.); (A.K.); (D.D.); (R.V.); (B.Z.)
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10
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Baylie T, Kasaw M, Getinet M, Getie G, Jemal M, Nigatu A, Ahmed H, Bogale M. The role of miRNAs as biomarkers in breast cancer. Front Oncol 2024; 14:1374821. [PMID: 38812786 PMCID: PMC11133523 DOI: 10.3389/fonc.2024.1374821] [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: 01/22/2024] [Accepted: 04/08/2024] [Indexed: 05/31/2024] Open
Abstract
Breast cancer (BC) is the second most common cause of deaths reported in women worldwide, and therefore there is a need to identify BC patients at an early stage as timely diagnosis would help in effective management and appropriate monitoring of patients. This will allow for proper patient monitoring and effective care. However, the absence of a particular biomarker for BC early diagnosis and surveillance makes it difficult to accomplish these objectives. miRNAs have been identified as master regulators of the molecular pathways that are emphasized in various tumors and that lead to the advancement of malignancies. Small, non-coding RNA molecules known as miRNAs target particular mRNAs to control the expression of genes. miRNAs dysregulation has been linked to the start and development of a number of human malignancies, including BC, since there is compelling evidence that miRNAs can function as tumor suppressor genes or oncogenes. The current level of knowledge on the role of miRNAs in BC diagnosis, prognosis, and treatment is presented in this review. miRNAs can regulate the tumorigenesis of BC through targeting PI3K pathway and can be used as prognostic or diagnostic biomarkers for BC therapy. Some miRNAs, like miR-9, miR-10b, and miR-17-5p, are becoming known as biomarkers of BC for diagnosis, prognosis, and therapeutic outcome prediction. Other miRNAs, like miR-30c, miR-187, and miR-339-5p, play significant roles in the regulation of hallmark functions of BC, including invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs, such as miR-155 and miR-210, are circulating in bodily fluids and are therefore of interest as novel, conveniently accessible, reasonably priced, non-invasive methods for the customized care of patients with BC.
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Affiliation(s)
- Temesgen Baylie
- Department of Biomedical Science, School of Medicine, Debre Markos University, Debre Markos, Ethiopia
| | - Mulugeta Kasaw
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Mamaru Getinet
- Department of Biomedical Science, School of Medicine, Debre Markos University, Debre Markos, Ethiopia
| | - Gedefaw Getie
- Department of Biomedical Science, School of Medicine, Debre Markos University, Debre Markos, Ethiopia
| | - Mohammed Jemal
- Department of Biomedical Science, School of Medicine, Debre Markos University, Debre Markos, Ethiopia
| | - Amare Nigatu
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Woldia University, Woldia, Ethiopia
| | - Hassen Ahmed
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Woldia University, Woldia, Ethiopia
| | - Mihiret Bogale
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, Wollo University, Wollo, Ethiopia
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11
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Fang X, Sun C, Dai P, Xian Z, Su W, Zheng C, Xing D, Xu X, You H. Capillary Force-Driven Quantitative Plasma Separation Method for Application of Whole Blood Detection Microfluidic Chip. MICROMACHINES 2024; 15:619. [PMID: 38793192 PMCID: PMC11122923 DOI: 10.3390/mi15050619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 04/27/2024] [Accepted: 04/29/2024] [Indexed: 05/26/2024]
Abstract
Separating plasma or serum from blood is essential for precise testing. However, extracting precise plasma quantities outside the laboratory poses challenges. A recent study has introduced a capillary force-driven membrane filtration technique to accurately separate small plasma volumes. This method efficiently isolates 100-200 μL of pure human whole blood with a 48% hematocrit, resulting in 5-30 μL of plasma with less than a 10% margin of error. The entire process is completed within 20 min, offering a simple and cost-effective approach to blood separation. This study has successfully addressed the bottleneck in self-service POCT, ensuring testing accuracy. This innovative method shows promise for clinical diagnostics and point-of-care testing.
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Affiliation(s)
| | | | | | | | | | | | | | - Xiaotian Xu
- School of Mechanical Engineering, Guangxi University, Nanning 530004, China; (X.F.); (C.S.); (P.D.); (Z.X.); (W.S.); (C.Z.); (D.X.)
| | - Hui You
- School of Mechanical Engineering, Guangxi University, Nanning 530004, China; (X.F.); (C.S.); (P.D.); (Z.X.); (W.S.); (C.Z.); (D.X.)
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12
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Lopes SR, Martins C, Santos IC, Teixeira M, Gamito É, Alves AL. Colorectal cancer screening: A review of current knowledge and progress in research. World J Gastrointest Oncol 2024; 16:1119-1133. [PMID: 38660635 PMCID: PMC11037045 DOI: 10.4251/wjgo.v16.i4.1119] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/16/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.
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Affiliation(s)
- Sara Ramos Lopes
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Claudio Martins
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Inês Costa Santos
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Madalena Teixeira
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Élia Gamito
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Ana Luisa Alves
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
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13
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Zhang N, Song GY, Yu QH, Fan XM, Zhang WS, Hu YJ, Chao TZ, Wu YY, Duan SY, Wang F, Du RP, Xu P. Evaluation of the lncRNA-miRNA-mRNA ceRNA network in lungs of miR-147 -/- mice. Front Pharmacol 2024; 15:1335374. [PMID: 38510653 PMCID: PMC10953689 DOI: 10.3389/fphar.2024.1335374] [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: 11/08/2023] [Accepted: 02/20/2024] [Indexed: 03/22/2024] Open
Abstract
Background: Previous studies have documented important roles for microRNA-147 (miR-147) in inflammation, radiation-induced injury, cancer, and a range of other diseases. Murine lungs exhibit high levels of miRNA, mRNA, and lncRNA expression. However, very little research to date has focused on the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks associated with miR-147, and the regulation of lncRNAs and miRNAs in this setting remains poorly understood. Methods: After establishing a miR-147-/- model mouse, samples of lung tissue were harvested for RNA-sequencing, and differentially expressed lncRNAs, miRNAs, and mRNAs were identified. The miRNA targets of these lncRNAs and the identified miRNAs were first overlapped to facilitate the prediction of target mRNAs, with analyses then examining the overlap between these targets and mRNAs that were differentially expressed. Then, these target mRNAs were subjected to pathway enrichment analyses. These results were ultimately used to establish a miR-147-related ceRNA network. Results: Relative to wild-type mice, the lungs of miR-147-/- mice exhibited 91, 43, and 71 significantly upregulated lncRNAs, miRNAs, and mRNAs, respectively, together with 114, 31, and 156 that were significantly downregulated. The lncRNA-miRNA-mRNA network established based on these results led to the identification of Kcnh6 as a differentially expressed hub gene candidate and enabled the identification of a range of regulatory relationships. KEGG pathway enrichment showed that the mRNA targets of differentially expressed lncRNAs and miRNAs in the mice were associated with tumor-related signaling, endometrial cancer, bladder cancer, and ErbB signaling. Conclusion: These results suggest that the identified ceRNA network in miR-147-/- mice shapes tumor-associated signaling activity, with miR-147 potentially regulating various lncRNAs and miRNAs through Kcnh6, ultimately influencing tumorigenesis. Future studies of the lncRNA, miRNA, and mRNA regulatory targets shown to be associated with miR-147 in the present study may ultimately lead to the identification of novel clinically relevant targets through which miR-147 shapes the pathogenesis of cancer and other diseases.
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Affiliation(s)
- Nan Zhang
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Gui-Yuan Song
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
- School of Pharmacy, Weifang Medical University, Weifang, Shandong, China
| | - Qing-Hua Yu
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
- School of Public Health, Weifang Medical University, Weifang, Shandong, China
| | - Xin-Ming Fan
- Department of Radiotherapy, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
| | - Wen-Shuo Zhang
- Department of Radiotherapy, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China
| | - Yong-Jian Hu
- Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, Henan, China
| | - Tian-Zhu Chao
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Yao-Yao Wu
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Shu-Yan Duan
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Fei Wang
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Rui-Peng Du
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
| | - Ping Xu
- Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China
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14
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Li W, Han G, Li F, Bu P, Hao Y, Huang L, Bai X. Cancer cell-derived exosomal miR-20a-5p inhibits CD8 + T-cell function and confers anti-programmed cell death 1 therapy resistance in triple-negative breast cancer. Cancer Sci 2024; 115:347-356. [PMID: 38129137 PMCID: PMC10859600 DOI: 10.1111/cas.16036] [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: 07/12/2023] [Revised: 11/06/2023] [Accepted: 11/09/2023] [Indexed: 12/23/2023] Open
Abstract
Circulating miRNAs (cirmiRNAs) can be packaged into the exosomes, participating in intercellular communication, which affects the malignant progression and therapy resistance of triple-negative breast cancer (TNBC). Currently, immune checkpoint inhibitors that regulate T-cell function, especially antibodies against programmed cell death 1 (PD-1) or its ligand PD-L1, are emerging as new promising therapy for TNBC patients. However, only very limited patients showed complete or partial response to anti-PD-1 treatment. Dysfunction of CD8+ T cells is one of the key reasons for the immune escape of TNBC. The regulation of exosome-derived cirmiRNAs on CD8+ T cells in TNBC deserves more investigation. Here, the cirmiR-20a-5p level was significantly upregulated in the plasma of TNBC patients and culture supernatant of TNBC cells. High abundance of cirmiR-20a-5p was correlated with a worse prognosis of TNBC. cirmiR-20a-5p was secreted in the form of exosomes by TNBC cells. Exosomal cirmiR-20a-5p was internalized into CD8+ T cells and resulted into the dysfunction of CD8+ T. A mechanism study uncovered that cirmiR-20a-5p targeted the nuclear protein ataxia-telangiectasia (NPAT) and decreased NPAT expression in CD8+ T cells. An in vivo xenograft mouse model showed that cirmiR-20a-5p conferred TNBC to anti-PD-1 treatment resistance. Collectively, these findings indicated that cirmiR-20a-5p released by TNBC cells via exosome promotes cancer cell growth and leads to the immunosuppression by inducing CD8+ T cell dysfunction. This study suggests that targeting cirmiR-20a-5p might be a novel strategy for overcoming the resistance of TNBC to anti-PD-1 immunotherapy.
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Affiliation(s)
- Weina Li
- Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
| | - Guohui Han
- Department of Breast Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
| | - Feng Li
- Department of Biochemistry and Molecular Biology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
| | - Peng Bu
- Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
| | - Yating Hao
- Department of Breast Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
| | - Li Huang
- Department of Breast Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
| | - Xiangdong Bai
- Department of Breast Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuanChina
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15
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Shen S, Zhang Y, Yang K, Chan H, Li W, Li X, Tian C, Niu Y. Flow-Rate-Insensitive Plasma Extraction by the Stabilization and Acceleration of Secondary Flow in the Ultralow Aspect Ratio Spiral Channel. Anal Chem 2023; 95:18278-18286. [PMID: 38016025 DOI: 10.1021/acs.analchem.3c04179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2023]
Abstract
Although microfluidic devices have made remarkable strides in blood cell separation, there is still a need for further development and improvement in this area. Herein, we present a novel ultralow aspect ratio (H/W = 1:36) spiral channel microfluidic device with ordered micro-obstacles for sheathless and flow-rate-insensitive blood cell separation. By introducing ordered micro-obstacles into the spiral microchannels, reduced magnitude fluctuations in secondary flow across different loops can be obtained through geometric confinement. As a result, the unique Dean-like secondary flow can effectively enhance the separation efficiency of particles in different sizes ranging from 3 to 15 μm. Compared to most existing microfluidic devices, our system offers several advantages of easy manufacturing, convenient operation, long-term stability, highly efficient performance (up to 99.70% rejection efficiency, including platelets), and most importantly, insensitivity to cell sizes as well as flow rates (allowing for efficient separation of different-sized blood cells in a wide flow rate from 1.00 to 2.50 mL/min). The unique characteristics, such as ultralow aspect ratio, sequential micro-obstacles, and controlled secondary flow, make our device a promising solution for practical plasma extraction in biomedical research and clinical applications.
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Affiliation(s)
- Shaofei Shen
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Yali Zhang
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Kai Yang
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Henryk Chan
- Department of Automatic Control and Systems Engineering, The University of Sheffield, Sheffield S10 2TN, U.K
| | - Weiwen Li
- Department of Breast, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, P. R. China
| | - Xiaoping Li
- Department of Breast, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, P. R. China
| | - Chang Tian
- School of Medicine, Anhui University of Science and Technology, Huainan 232001, Anhui, P. R. China
| | - Yanbing Niu
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
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16
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Shen S, Bai H, Wang X, Chan H, Niu Y, Li W, Tian C, Li X. High-Throughput Blood Plasma Extraction in a Dimension-Confined Double-Spiral Channel. Anal Chem 2023; 95:16649-16658. [PMID: 37917001 DOI: 10.1021/acs.analchem.3c03002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
Abstract
Microfluidic technologies enabling the control of secondary flow are essential for the successful separation of blood cells, a process that is beneficial for a wide range of medical research and clinical diagnostics. Herein, we introduce a dimension-confined microfluidic device featuring a double-spiral channel designed to regulate secondary flows, thereby enabling high-throughput isolation of blood for plasma extraction. By integrating a sequence of micro-obstacles within the double-spiral microchannels, the stable and enhanced Dean-like secondary flow across each loop can be generated. This setup consequently prompts particles of varying diameters (3, 7, 10, and 15 μm) to form different focusing states. Crucially, this system is capable of effectively separating blood cells of different sizes with a cell throughput of (2.63-3.36) × 108 cells/min. The concentration of blood cells in outlet 2 increased 3-fold, from 1.46 × 108 to 4.37 × 108, while the number of cells, including platelets, exported from outlets 1 and 3 decreased by a factor of 608. The engineering approach manipulating secondary flow for plasma extraction points to simplicity in fabrication, ease of operation, insensitivity to cell size, high throughput, and separation efficiency, which has potential utility in propelling the development of miniaturized diagnostic devices in the field of biomedical science.
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Affiliation(s)
- Shaofei Shen
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Hanjie Bai
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Xin Wang
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Henryk Chan
- Department of Automatic Control and Systems Engineering, The University of Sheffield, Sheffield S10 2TN, U.K
| | - Yanbing Niu
- Shanxi Key Lab for Modernization of TCVM, College of Life Science, Shanxi Agricultural University, Taiyuan 030000, Shanxi, P. R. China
| | - Weiwen Li
- Department of Breast, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, P. R. China
| | - Chang Tian
- School of Medicine, Anhui University of Science and Technology, Huainan 232001, Anhui, P. R. China
| | - Xiaoping Li
- Department of Breast, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, P. R. China
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17
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Hong F, Li N, Feng Z, Zheng Y, Zhu C, Zhang F. Exosomal microRNAs as novel diagnostic biomarkers in breast cancer: A systematic evaluation and meta-analysis. Asian J Surg 2023; 46:4727-4736. [PMID: 37301624 DOI: 10.1016/j.asjsur.2023.05.115] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 04/30/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Circulating tumor-derived exosomal microRNAs (miRNAs) play a key role in the development of cancer. We aimed to assess the diagnostic value of circulating exosomal miRNAs in breast cancer (BC). A computer search was conducted for clinical studies on exosomal miRNA diagnosis of breast cancer published in Wanfang, CNKI, China Biology Medicine disc, VIP, Web of Science, Cochrane Library, PubMed, and Embase built up to August 16, 2022. True/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain pooled sensitivities, specificities, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CI). The meta-analysis included 7 articles including 348 Asian patients and 260 controls. All miRNAs were quantified using qRT-PCR assays. The sensitivity and specificity of the combination were 0.67 (95% CI = 0.64-0.71) and 0.81 (95% CI = 0.77-0.86), respectively. The combined DOR was 10.2 (95% CI = 6.00-16.74). The combined AUC(area under the subject operating characteristic curve) was 0.83 (0.91-0.96). In conclusion, exosomal-derived miRNA can be a good indicator to improve the diagnosis of breast cancer.
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Affiliation(s)
- Fangcheng Hong
- Department of Thyroid and Breast Surgery, Hebei General Hospital Affiliated to Hebei North University, Shijiazhuang, 050051, Hebei Province, China
| | - Ning Li
- Department of Thyroid and Breast Surgery, Hebei General Hospital Affiliated to Hebei Medicine University, Shijiazhuang, 050051, Hebei Province, China
| | - Zheming Feng
- Department of Thyroid and Breast Surgery, Hebei General Hospital Affiliated to Hebei Medicine University, Shijiazhuang, 050051, Hebei Province, China
| | - Yuxin Zheng
- Department of Thyroid and Breast Surgery, Hebei General Hospital Affiliated to North China University of Science and Technology, Shijiazhuang, 050051, Hebei Province, China
| | - Chunyue Zhu
- Department of Thyroid and Breast Surgery, Hebei General Hospital Affiliated to North China University of Science and Technology, Shijiazhuang, 050051, Hebei Province, China
| | - Fenghua Zhang
- Department of Thyroid and Breast Surgery, Hebei General Hospital, No.348 Peace West Road, Shijiazhuang, 050051, Hebei Province, China.
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18
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Kumar S, Dhar R, Kumar LBSS, Shivji GG, Jayaraj R, Devi A. Theranostic signature of tumor-derived exosomes in cancer. Med Oncol 2023; 40:321. [PMID: 37798480 DOI: 10.1007/s12032-023-02176-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 08/29/2023] [Indexed: 10/07/2023]
Abstract
Cancer is the most challenging global health crisis. In the recent times, studies on extracellular vesicles (EVs) are adding a new chapter to cancer research and reports on EVs explores cancer in a new dimension. Exosomes are a group of subpopulations of EVs. It originates from the endosomes and carries biologically active molecules to the neighboring cells which in turn transforms the recipient cell activity. In general, it plays a role in cellular communication. The correlation between exosomes and cancer is fascinating. Tumor-derived exosomes (TEXs) play a dynamic role in cancer progression and are associated with uncontrolled cell growth, angiogenesis, immune suppression, and metastasis. Its molecular cargo is an excellent source of cancer biomarkers. Several advanced molecular profiling approaches assist in exploring the TEXs in depth. This paves the way for a strong foundation for identifying and detecting more specific and efficient biomarkers. TEXs are also gaining importance in scientific society for its role in cancer therapy and several clinical trials based on TEXs is a proof of its significance. In this review, we have highlighted the role of TEXs in mediating immune cell reprogramming, cancer development, metastasis, EMT, organ-specific metastasis, and its clinical significance in cancer theranostics. TEXs profiling is an effective method to understand the complications associated with cancer leading to good health and well-being of the individual and society as a whole.
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Affiliation(s)
- Samruti Kumar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, 603203, India
| | - Rajib Dhar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, 603203, India
| | - Lokesh Babu Sirkali Suresh Kumar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, 603203, India
| | - Gauresh Gurudas Shivji
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, 603203, India
| | - Rama Jayaraj
- Jindal Institute of Behavioral Sciences (JIBS), Jindal Global Institution of Eminence Deemed to Be University, 28, Sonipat, 131001, India
- Director of Clinical Sciences, Northern Territory Institute of Research and Training, Darwin, NT, 0909, Australia
| | - Arikketh Devi
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, 603203, India.
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Benlhachemi S, Abouqal R, Coleman N, Murray MJ, Khattab M, El fahime E. Circulating microRNA profiles in Wilms tumour (WT): A systematic review and meta-analysis of diagnostic test accuracy. Noncoding RNA Res 2023; 8:413-425. [PMID: 37305178 PMCID: PMC10247954 DOI: 10.1016/j.ncrna.2023.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/24/2023] [Accepted: 05/25/2023] [Indexed: 06/13/2023] Open
Abstract
Background Wilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature. Methods Regardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis. Results Qualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT. Conclusions Circulating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype. Prospero registration number CRD42022301597.
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Affiliation(s)
- Sara Benlhachemi
- Laboratory of Genomics and Molecular Epidemiology of Genetic Diseases (GE2MG). Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco
- Molecular Biology and Functional Genomics Platform, National Center for Scientific and Technical Research, Rabat, Morocco
| | - Redouane Abouqal
- Biostatistics Laboratory, Clinical Epidemiology Research. Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco
| | - Nicholas Coleman
- Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Matthew Jonathan Murray
- Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK
- Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, UK
| | - Mohammed Khattab
- Department of Paediatric Haematology and Oncology, Abulcasis International University of Health Sciences, Rabat, Morocco
| | - Elmostafa El fahime
- Molecular Biology and Functional Genomics Platform, National Center for Scientific and Technical Research, Rabat, Morocco
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20
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Lee LM, Bhatt KH, Haithcock DW, Prabhakarpandian B. Blood component separation in straight microfluidic channels. BIOMICROFLUIDICS 2023; 17:054106. [PMID: 37854890 PMCID: PMC10581738 DOI: 10.1063/5.0176457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/03/2023] [Indexed: 10/20/2023]
Abstract
Separation of blood components is required in many diagnostic applications and blood processes. In laboratories, blood is usually fractionated by manual operation involving a bulk centrifugation equipment, which significantly increases logistic burden. Blood sample processing in the field and resource-limited settings cannot be readily implemented without the use of microfluidic technology. In this study, we developed a small footprint, rapid, and passive microfluidic channel device that relied on margination and inertial focusing effects for blood component separation. No blood dilution, lysis, or labeling step was needed as to preserve sample integrity. One main innovation of this work was the insertion of fluidic restrictors at outlet ports to divert the separation interface into designated outlet channels. Thus, separation efficiency was significantly improved in comparison to previous works. We demonstrated different operation modes ranging from platelet or plasma extraction from human whole blood to platelet concentration from platelet-rich plasma through the manipulation of outlet port fluidic resistance. Using straight microfluidic channels with a high aspect ratio rectangular cross section, we demonstrated 95.4% platelet purity extracted from human whole blood. In plasma extraction, 99.9% RBC removal rate was achieved. We also demonstrated 2.6× concentration of platelet-rich plasma solution to produce platelet concentrate. The extraction efficiency and throughput rate are scalable with continuous and clog-free recirculation operation, in contrast to other blood fractionation approaches using filtration membranes or affinity-based purification methods. Our microfluidic blood separation method is highly tunable and versatile, and easy to be integrated into multi-step blood processing and advanced sample preparation workflows.
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Affiliation(s)
- Lap Man Lee
- CFD Research Corporation, Huntsville, Alabama 35806, USA
| | - Ketan H. Bhatt
- CFD Research Corporation, Huntsville, Alabama 35806, USA
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Felekkis K, Pieri M, Papaneophytou C. Exploring the Feasibility of Circulating miRNAs as Diagnostic and Prognostic Biomarkers in Osteoarthritis: Challenges and Opportunities. Int J Mol Sci 2023; 24:13144. [PMID: 37685951 PMCID: PMC10487837 DOI: 10.3390/ijms241713144] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by progressive cartilage degradation and joint inflammation. As the most common aging-related joint disease, OA is marked by inadequate extracellular matrix synthesis and the breakdown of articular cartilage. However, traditional diagnostic methods for OA, relying on clinical assessments and radiographic imaging, often need to catch up in detecting early-stage disease or i accurately predicting its progression. Consequently, there is a growing interest in identifying reliable biomarkers that can facilitate early diagnosis and prognosis of OA. MicroRNAs (miRNAs) have emerged as potential candidates due to their involvement in various cellular processes, including cartilage homeostasis and inflammation. This review explores the feasibility of circulating miRNAs as diagnostic and prognostic biomarkers in OA, focusing on knee OA while shedding light on the challenges and opportunities associated with their implementation in clinical practice.
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Affiliation(s)
| | | | - Christos Papaneophytou
- Department of Life Sciences, School of Life and Health Sciences, University of Nicosia, 46 Makedonitissas Avenue, Nicosia 2417, Cyprus; (K.F.); (M.P.)
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Samad MIA, Ponnuthurai DR, Badrudin SI, Ali MAM, Razak MAA, Buyong MR, Latif R. Migration Study of Dielectrophoretically Manipulated Red Blood Cells in Tapered Aluminium Microelectrode Array: A Pilot Study. MICROMACHINES 2023; 14:1625. [PMID: 37630162 PMCID: PMC10457829 DOI: 10.3390/mi14081625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/29/2023] [Accepted: 07/19/2023] [Indexed: 08/27/2023]
Abstract
Dielectrophoresis (DEP) is one of the microfluid-based techniques that can manipulate the red blood cells (RBC) for blood plasma separation, which is used in many medical screening/diagnosis applications. The tapered aluminium microelectrode array (TAMA) is fabricated for potential sensitivity enhancement of RBC manipulation in lateral and vertical directions. In this paper, the migration properties of dielectrophoretically manipulated RBC in TAMA platform are studied at different peak-to-peak voltage (Vpp) and duration supplied onto the microelectrodes. Positive DEP manipulation is conducted at 440 kHz with the RBC of 4.00 ± 0.2 µm average radius attracted to the higher electric field intensity regions, which are the microelectrodes. High percentage of RBC migration occurred at longer manipulation time and high electrode voltage. During DEP manipulation, the RBC are postulated to levitate upwards, experience the electro-orientation mechanism and form the pearl chains before migrating to the electrodes. The presence of external forces other than the dielectrophoretic force may also affect the migration response of RBC. The safe operating limit of 10 Vpp and manipulation duration of ≤50 s prevent RBC rupture while providing high migration percentage. It is crucial to define the safe working region for TAMA devices that manipulate small RBC volume (~10 µL).
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Affiliation(s)
- Muhammad Izzuddin Abd Samad
- Institute of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia; (M.I.A.S.); (D.R.P.); (S.I.B.); (M.R.B.)
| | - Darven Raj Ponnuthurai
- Institute of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia; (M.I.A.S.); (D.R.P.); (S.I.B.); (M.R.B.)
| | - Syazwani Izrah Badrudin
- Institute of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia; (M.I.A.S.); (D.R.P.); (S.I.B.); (M.R.B.)
| | - Mohd Anuar Mohd Ali
- School of Electrical Engineering, Universiti Teknologi Malaysia (UTM), Skudai 81310, Johor, Malaysia; (M.A.M.A.); (M.A.A.R.)
| | - Mohd Azhar Abdul Razak
- School of Electrical Engineering, Universiti Teknologi Malaysia (UTM), Skudai 81310, Johor, Malaysia; (M.A.M.A.); (M.A.A.R.)
| | - Muhamad Ramdzan Buyong
- Institute of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia; (M.I.A.S.); (D.R.P.); (S.I.B.); (M.R.B.)
| | - Rhonira Latif
- Institute of Microengineering and Nanoelectronics (IMEN), Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia; (M.I.A.S.); (D.R.P.); (S.I.B.); (M.R.B.)
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Kuscu C, Mallisetty Y, Naik S, Han Z, Berta CJ, Kuscu C, Kovesdy CP, Sumida K. Circulating microRNA Profiles for Premature Cardiovascular Death in Patients with Kidney Failure with Replacement Therapy. J Clin Med 2023; 12:5010. [PMID: 37568412 PMCID: PMC10419472 DOI: 10.3390/jcm12155010] [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: 06/27/2023] [Revised: 07/21/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
INTRODUCTION Patients with kidney failure with replacement therapy (KFRT) suffer from a disproportionately high cardiovascular disease burden. Circulating small non-coding RNAs (c-sncRNAs) have emerged as novel epigenetic regulators and are suggested as novel biomarkers and therapeutic targets for cardiovascular disease; however, little is known about the associations of c-sncRNAs with premature cardiovascular death in KFRT. METHODS In a pilot case-control study of 50 hemodialysis patients who died of cardiovascular events as cases, and 50 matched hemodialysis controls who remained alive during a median follow-up of 2.0 years, we performed c-sncRNAs profiles using next-generation sequencing to identify differentially expressed circulating microRNAs (c-miRNAs) between the plasma of cases and that of controls. mRNA target prediction and pathway enrichment analysis were performed to examine the functional relevance of differentially expressed c-miRNAs to cardiovascular pathophysiology. The association of differentially expressed c-miRNAs with cardiovascular mortality was examined using multivariable conditional logistic regression. RESULTS The patient characteristics were similar between cases and controls, with a mean age of 63 years, 48% male, and 54% African American in both groups. We detected a total of 613 miRNAs in the plasma, among which five miRNAs (i.e., miR-129-1-5p, miR-500b-3p, miR-125b-1-3p, miR-3648-2-5p, and miR-3150b-3p) were identified to be differentially expressed between cases and controls with cut-offs of p < 0.05 and log2 fold-change (log2FC) > 1. When using more stringent cut-offs of p-adjusted < 0.05 and log2FC > 1, only miR-129-1-5p remained significantly differentially expressed, with higher levels of miR-129-1-5p in the cases than in the controls. The pathway enrichment analysis using predicted miR-129-1-5p mRNA targets demonstrated enrichment in adrenergic signaling in cardiomyocytes, arrhythmogenic right ventricular cardiomyopathy, and oxytocin signaling pathways. In parallel, the circulating miR-129-1-5p levels were significantly associated with the risk of cardiovascular death (adjusted OR [95% CI], 1.68 [1.01-2.81] for one increase in log-transformed miR-129-1-5p counts), independent of potential confounders. CONCLUSIONS Circulating miR-129-1-5p may serve as a novel biomarker for premature cardiovascular death in KFRT.
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Affiliation(s)
- Canan Kuscu
- Transplant Research Institute, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (S.N.); (C.K.)
| | - Yamini Mallisetty
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (Y.M.); (Z.H.); (C.J.B.); (C.P.K.)
| | - Surabhi Naik
- Transplant Research Institute, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (S.N.); (C.K.)
| | - Zhongji Han
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (Y.M.); (Z.H.); (C.J.B.); (C.P.K.)
| | - Caleb J. Berta
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (Y.M.); (Z.H.); (C.J.B.); (C.P.K.)
| | - Cem Kuscu
- Transplant Research Institute, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (S.N.); (C.K.)
| | - Csaba P. Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (Y.M.); (Z.H.); (C.J.B.); (C.P.K.)
- Nephrology Section, Memphis VA Medical Center, Memphis, TN 38104, USA
| | - Keiichi Sumida
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; (Y.M.); (Z.H.); (C.J.B.); (C.P.K.)
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You J, Xia H, Huang Z, He R, Zhao X, Chen J, Liu S, Xu Y, Cui Y. Research progress of circulating non-coding RNA in diagnosis and treatment of hepatocellular carcinoma. Front Oncol 2023; 13:1204715. [PMID: 37546394 PMCID: PMC10400719 DOI: 10.3389/fonc.2023.1204715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/28/2023] [Indexed: 08/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly malignant tumor that carries a significant risk of morbidity and mortality. This type of cancer is prevalent in Asia due to the widespread presence of risk factors. Unfortunately, HCC often goes undetected until it has reached an advanced stage, making early detection and treatment critical for better outcomes. Alpha-fetoprotein (AFP) is commonly used in clinical practice for diagnosing HCC, but its sensitivity and specificity are limited. While surgery and liver transplantation are the main radical treatments, drug therapy and local interventions are better options for patients with advanced HCC. Accurately assessing treatment efficacy and adjusting plans in a timely manner can significantly improve the prognosis of HCC. Non-coding RNA gene transcription products cannot participate in protein production, but they can regulate gene expression and protein function through the regulation of transcription and translation processes. These non-coding RNAs have been found to be associated with tumor development in various types of tumors. Noncoding RNA released by tumor or blood cells can circulate in the blood and serve as a biomarker for diagnosis, prognosis, and efficacy assessment. This article explores the unique role of circulating noncoding RNA in HCC from various perspectives.
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Affiliation(s)
- Junqi You
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Haoming Xia
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ziyue Huang
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Risheng He
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xudong Zhao
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jiali Chen
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Sidi Liu
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yi Xu
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yunfu Cui
- Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Zhu J, Luo J, Ma Y. Screening of serum exosome markers for colorectal cancer based on Boruta and multi-cluster feature selection algorithms. Mol Cell Toxicol 2023. [DOI: 10.1007/s13273-023-00348-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2023]
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Govindan B, Sabri MA, Hai A, Banat F, Haija MA. A Review of Advanced Multifunctional Magnetic Nanostructures for Cancer Diagnosis and Therapy Integrated into an Artificial Intelligence Approach. Pharmaceutics 2023; 15:868. [PMID: 36986729 PMCID: PMC10058002 DOI: 10.3390/pharmaceutics15030868] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 03/06/2023] [Accepted: 03/07/2023] [Indexed: 03/10/2023] Open
Abstract
The new era of nanomedicine offers significant opportunities for cancer diagnostics and treatment. Magnetic nanoplatforms could be highly effective tools for cancer diagnosis and treatment in the future. Due to their tunable morphologies and superior properties, multifunctional magnetic nanomaterials and their hybrid nanostructures can be designed as specific carriers of drugs, imaging agents, and magnetic theranostics. Multifunctional magnetic nanostructures are promising theranostic agents due to their ability to diagnose and combine therapies. This review provides a comprehensive overview of the development of advanced multifunctional magnetic nanostructures combining magnetic and optical properties, providing photoresponsive magnetic platforms for promising medical applications. Moreover, this review discusses various innovative developments using multifunctional magnetic nanostructures, including drug delivery, cancer treatment, tumor-specific ligands that deliver chemotherapeutics or hormonal agents, magnetic resonance imaging, and tissue engineering. Additionally, artificial intelligence (AI) can be used to optimize material properties in cancer diagnosis and treatment, based on predicted interactions with drugs, cell membranes, vasculature, biological fluid, and the immune system to enhance the effectiveness of therapeutic agents. Furthermore, this review provides an overview of AI approaches used to assess the practical utility of multifunctional magnetic nanostructures for cancer diagnosis and treatment. Finally, the review presents the current knowledge and perspectives on hybrid magnetic systems as cancer treatment tools with AI models.
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Affiliation(s)
- Bharath Govindan
- Department of Chemical Engineering, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
- Department of Chemistry, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
| | - Muhammad Ashraf Sabri
- Department of Chemical Engineering, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
| | - Abdul Hai
- Department of Chemical Engineering, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
| | - Fawzi Banat
- Department of Chemical Engineering, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
| | - Mohammad Abu Haija
- Department of Chemical Engineering, Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
- Advanced Materials Chemistry Center (AMCC), Khalifa University of Science and Technology, Abu Dhabi P.O. Box 127788, United Arab Emirates
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Giordano R, Gerra MC, Okutani H, Lo Vecchio S, Stensballe A, Petersen KKS, Arendt-Nielsen L. The temporal expression of circulating microRNAs after acute experimental pain in humans. Eur J Pain 2023; 27:366-377. [PMID: 36453122 DOI: 10.1002/ejp.2062] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/17/2022] [Accepted: 11/27/2022] [Indexed: 12/04/2022]
Abstract
BACKGROUND MicroRNAs (miRNAs) can modulate several biological systems, including the pain system. This study aimed to evaluate the temporal expression of circulating miRNAs in the plasma of healthy volunteers as a marker for epigenetic changes before and after an acute, experimental, pain provocation by intramuscular hypertonic saline injection. METHODS Twenty volunteers were randomly allocated into two groups and received either hypertonic (pain) or isotonic (control) saline injection in the first dorsal interosseous muscle of their dominant hand. Pain intensity was continuously recorded for 20 minutes after injection on a VAS scale from 0 to 100 (0 indicates no pain and 100 the worst imaginable pain). Blood samples were taken at baseline, 30 minutes, 3 hours, and 24 hours post-injection, and plasma was separated. MiRNA extracts were used for RNA sequencing with the Illumina NextSeq platform. MiRNA transcripts were compared between the pain and the no-pain, control group at every time point. Significant differences were considered when folds were >2 and the False Discovery Rate was p < 0.05. RESULTS After 30 minutes, 4 miRNAs were significantly altered in the pain group compared to controls, which increased to 24 after 3 hours and to 42 after 24 hours from baseline (p < 0.0001). Two miRNAs were consistently upregulated throughout the experiment. Enrichment analysis showed significant miRNAs involved in brain perception of pain, brain signalling and response to stimuli. CONCLUSIONS This exploratory study is the first to report on the temporal expression of circulating miRNAs after an acute, human experimental muscle pain model. SIGNIFICANCE This exploratory study evaluated the temporal profile of circulating miRNAs in the plasma of healthy subjects after acute experimental pain. Several miRNAs were altered in subjects at the times of follow-up after the acute pain model when compared to controls. MiRNAs previously associated with pain processes were altered in the pain group. Our results, by showing the fast and prolonged modifications of miRNA elicited by the acute experimental pain model, add new perspectives to the topic of epigenetics and pain.
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Affiliation(s)
- Rocco Giordano
- Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Department of Health Science and Technology, Faculty of Medicine, Aalborg, Denmark
| | - Maria Carla Gerra
- Department of Chemistry, Life science, and Environmental Sustainability, University of Parma, Parma, Italy
| | - Hiroai Okutani
- Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Department of Health Science and Technology, Faculty of Medicine, Aalborg, Denmark
- Department of Anesthesiology and Pain Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Silvia Lo Vecchio
- Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Department of Health Science and Technology, Faculty of Medicine, Aalborg, Denmark
| | - Allan Stensballe
- Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Kristian Kjaer-Staal Petersen
- Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Department of Health Science and Technology, Faculty of Medicine, Aalborg, Denmark
- Center for Mathematical Modeling of Knee Osteoarthritis (MathKOA), Aalborg University, Department of Material and Production, Faculty of Engineering and Science, Aalborg, Denmark
| | - Lars Arendt-Nielsen
- Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Department of Health Science and Technology, Faculty of Medicine, Aalborg, Denmark
- Department of Gastroenterology & Hepatology, (Mech-Sense), Aalborg University Hospital, Aalborg, Denmark
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A circulating microRNA panel as a novel dynamic monitor for oral squamous cell carcinoma. Sci Rep 2023; 13:2000. [PMID: 36737651 PMCID: PMC9898506 DOI: 10.1038/s41598-023-28550-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 01/19/2023] [Indexed: 02/05/2023] Open
Abstract
Oral squamous cell carcinoma (OSCC) has high recurrence and mortality rates despite advances in diagnosis and treatment. Therefore, it is necessary to identify new biomarkers for early detection, efficient monitoring, and prognosis prediction. Since microRNA (miRNA) is stable and detectable in serum, it has been reported to inform the diagnosis and monitor disease progression through liquid biopsy. In this study, a circulating specific miRNA panel in OSCC patients was developed, and its usefulness as a dynamic monitor was validated. Small RNAs were extracted from the serum of OSCC patients (n = 4) and normal controls (n = 6) and profiled using next-generation sequencing. NGS identified 42 differentially expressed miRNAs (DEmiRNAs) in serum between patients with OSCC and healthy controls, with threefold differences (p < 0.05). Combining the 42 DEmiRNAs and The Cancer Genome Atlas (TCGA) databases OSCC cohort, 9 overlapping DEmiRNAs were screened out. Finally, 4 significantly up-regulated miRNAs (miR-92a-3p, miR-92b-3p, miR-320c and miR-629-5p) were identified from OSCC patients via validation in the Chungnam National University Hospital cohort. Application of the specific miRNA panel for distinguishing OSCC patients from healthy controls produced specificity and sensitivity of 97.8 and 74%, respectively. In addition, the serum levels of these 4 miRNAs significantly decreased after complete surgical resection and increased after recurrence. We suggest that circulating 4-miRNA panel might be promising non-invasive predictors for diagnosing and monitoring the progression of patients with OSCC.
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Ho CSH, Soh MWT, Tay GWN. The diagnostic utility of miRNA and elucidation of pathological mechanisms in major depressive disorder. Compr Psychiatry 2023; 121:152363. [PMID: 36580691 DOI: 10.1016/j.comppsych.2022.152363] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/20/2022] [Accepted: 12/21/2022] [Indexed: 12/24/2022] Open
Abstract
AIMS Our study aims to explore how miRNAs can elucidate the molecular mechanisms of major depressive disorder (MDD) by comparing the miRNA levels in the blood serum of patients with depression and healthy individuals. It also explores the potential of miRNAs to differentiate between depressed patients and healthy controls. METHODS 60 healthy controls (n = 45 females) were matched to 60 depressed patients (n = 10 unmedicated) for age (±7), sex, ethnicity, and years of education. Depression severity was measured using the Hamilton Depression Rating Scale, and venous blood was collected using PAXgene Blood RNA tubes for miRNA profiling. To further identify the depression-related biological pathways that are influenced by differentially expressed miRNAs, networks were constructed using QIAGEN Ingenuity Pathway Analysis. Receiver operating characteristic (ROC) analyses were also conducted to examine the discriminative ability of miRNAs to distinguish between depressed and healthy individuals. RESULTS Six miRNAs (miR-542-3p, miR-181b-3p, miR-190a-5p, miR-33a-3p, miR-3690 and miR-6895-3p) showed to be considerably down-regulated in unmedicated depressed patients relative to healthy controls. miR-542-3p, in particular, also has experimentally verified mRNA targets that are predicted to be associated with MDD. ROC analyses found that a panel combining miR-542-3p, miR-181b-3p and miR-3690 produced an area under the curve value of 0.67 in distinguishing between depressed and healthy individuals. CONCLUSIONS miRNAs - most notably, miR-542-3p, miR-181b-3p and miR-3690 - may be biomarkers with targets that are implicated in the pathophysiology of depression. They could also be used to distinguish between depressed and healthy individuals with reasonable accuracy.
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Affiliation(s)
- Cyrus Su Hui Ho
- Department of Psychological Medicine, National University Health System, Singapore, Singapore; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
| | - Michelle Wei Ting Soh
- Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Gabrielle Wann Nii Tay
- Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Functions and cellular signaling by ribosomal extracellular RNA (rexRNA): Facts and hypotheses on a non-typical DAMP. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2023; 1870:119408. [PMID: 36503009 DOI: 10.1016/j.bbamcr.2022.119408] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 11/07/2022] [Accepted: 11/30/2022] [Indexed: 12/13/2022]
Abstract
Upon microbial infections with the subsequent host response of innate immunity, a variety of fragmented RNA- and DNA-based "Pathogen-associated molecular patterns" (PAMPs) are recognized mainly by endosomal or cytoplasmic host cell "Pattern recognition receptors" (PRRs), particularly "Toll-like receptors" (TLRs). Concomitantly, various self-extracellular RNA species (exRNAs) are present in extracellular body fluids where they contribute to diverse physiological and homeostatic processes. In principle, such exRNAs, including the most abundant one, ribosomal exRNA (rexRNA), are designated as "Danger-associated molecular patterns" (DAMPs) and are prevented by e.g. natural modifications from uncontrolled signaling via TLRs to avoid hyper-inflammatory responses or autoimmunity. Upon cellular stress or tissue damage/necrosis, the levels and composition of released self-exRNA species, either in free form, in complex with proteins or in association with extracellular vesicles (EVs), can change considerably. Among the self-exRNAs, rexRNA is considered as a non-typical DAMP, since it may induce inflammatory responses by cell membrane receptors, both in the absence or presence of PAMPs. Yet, its mode of receptor activation to mount inflammatory responses remains obscure. RexRNA also serves as a universal damaging factor in cardiovascular and other diseases independent of PRRs. In general, RNase1 provides a profound antagonist in these pathologies and in rexRNA-mediated inflammatory cell responses. Based on the extrapolation of the here described aspects of rexRNA-biology, further activities of this molecular entity are hypothesized that may stimulate additional research in this area.
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Pourgholamali B, Sohrabi B, Salbi M, Akbari S, Rastan I, Sayaf M, Jalil AT, Kadhim MM, Sheervalilou R, Mehrzad N. Bioinformatic Analysis Divulged Novel Prognostic Circulating MicroRNAs and Their Potential Target Genes in Breast Cancer. Appl Biochem Biotechnol 2023; 195:283-297. [PMID: 36074234 DOI: 10.1007/s12010-022-04151-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2022] [Indexed: 01/13/2023]
Abstract
Breast cancer (BC) is both an inherited and environmental-based disease which is the leading cause of death among women. Early detection of BC can prevent invasion and metastasis in patients. Currently, researchers endeavor to find non-invasive biological markers from body fluids. Circulating non-coding RNAs such as microRNAs (miRNAs) can potentially be valuable prognostic and detective biomarkers. To identify novel miRNA-based biomarkers, we utilized bioinformatic tools. To reach this goal, the miRNA expression profiles of GSE31309, GSE 44,281, GSE98181, and GSE118782 were analyzed through a limma package of R. Target gene prediction of differentially expressed miRNAs, called differentially expressed miRNAs (DEMs), between samples of healthy individuals and BC patients was implemented through Multimir package of R. Functional enrichment analysis of predicted target genes through Enrich R (online database) revealed that most of the genes are enriched in the mitochondrial outer membrane for cellular component, intrinsic apoptotic signaling regulations for biological processes, transcription co-receptor activity for molecular functions, and dopaminergic synapse pathway. Furthermore, our survival analysis results revealed that miR-29c and mir-361 have the potential to serve as prognostic biomarkers.
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Affiliation(s)
- Babak Pourgholamali
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Behnoush Sohrabi
- Department of Biology, Faculty of Sciences, Arak University, Arak, Iran
| | - Mandana Salbi
- Department of Microbiology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | | | - Iman Rastan
- Department of Electronic and Electrical Engineering, Shiraz Azad University, Shiraz, Iran
| | - Masoud Sayaf
- Azad University Central Tehran Branch Faculty of Basic Sciences, Department of Cellular and Molecular Biology, Tehran, Iran
| | - Abduladheem Turki Jalil
- Medical Laboratories Techniques Department, Al-Mustaqbal University College, Babylon, Hilla, 51001, Iraq
| | - Mustafa M Kadhim
- Medical Laboratory Techniques Department, Al-Farahidi University, Baghdad, Iraq.,Department of Dentistry, Kut University College, Kut, Wasit, Iraq
| | - Roghayeh Sheervalilou
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Nazanin Mehrzad
- Department of Biology, Science and Research Branch Islamic Azad university, Tehran, Iran.
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Rahmati A, Mafi A, Soleymani F, Babaei Aghdam Z, Masihipour N, Ghezelbash B, Asemi R, Aschner M, Vakili O, Homayoonfal M, Asemi Z, Sharifi M, Azadi A, Mirzaei H, Aghadavod E. Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia. Front Oncol 2023; 13:1149187. [PMID: 37124518 PMCID: PMC10140500 DOI: 10.3389/fonc.2023.1149187] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 03/29/2023] [Indexed: 05/02/2023] Open
Abstract
Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.
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Affiliation(s)
- Atefe Rahmati
- Department of Hematology and Blood Banking, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Basic Sciences, Faculty of Medicine, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Firooze Soleymani
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Babaei Aghdam
- Imaging Sciences Research Group, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Niloufar Masihipour
- Department of Medicine, Lorestan University of Medical Science, Lorestan, Iran
| | - Behrooz Ghezelbash
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Asemi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mina Homayoonfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Mehran Sharifi
- Department of Internal Medicine, School of Medicine, Cancer Prevention Research Center, Seyyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abbas Azadi
- Department of Internal Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- *Correspondence: Abbas Azadi, ; Esmat Aghadavod, ; Hamed Mirzaei, ;
| | - Esmat Aghadavod
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
- Department of Clinical Biochemistry, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
- *Correspondence: Abbas Azadi, ; Esmat Aghadavod, ; Hamed Mirzaei, ;
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Heydari Z, Moudi E, Sadeghi F, Hajiahmadi M, Rezatabar S, Neamati N, Parsian H. Circulating plasma miR222-3P status and its potential diagnostic performance in prostate cancer. J Gene Med 2022; 24:e3459. [PMID: 36279183 DOI: 10.1002/jgm.3459] [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: 05/25/2022] [Revised: 08/23/2022] [Accepted: 10/16/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Although studies suggest that miR222-3p is dysregulated in prostate cancer (PC) cells and tissues, the possible changes in the level of miR222-3p in the plasma samples of PC patients remained unclear. The present study aimed to evaluate the diagnostic value of the plasma miR222-3p expression level as a potential biomarker in PC, benign prostatic hyperplasia (BPH) and healthy people. METHODS Blood samples were collected from 100 adult males (54 patients with PC, 27 patients with BPH and 19 healthy individuals) referred to our affiliated hospital. The expression level of miR222-3p was evaluated using a quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic curves were used to evaluate miR222-3p diagnostic accuracy for discriminating between the PC, BPH and healthy individuals. RESULTS The expression level of miR222-3p was significantly higher in PC patients compared to healthy individuals as a fold change of 5.3 (p = 0.009), but not for BPH individuals. The diagnostic value of the plasma miR222-3p for discrimination of the PC patients from healthy individuals was reasonable [cut-off value (fold change relative to miR16-5p) = 1.69, area under the curve = 0.73, sensitivity = 0.75 and specificity = 0.74]. CONCLUSIONS Circulating plasma miR-222-3p significantly upregulated in PC patients, but not in BPH ones. Besides these preliminary results showed that miR222-3p has the potential to discriminate PC patients from healthy ones. Addittional studies with a larger sample size are required to confirm these data.
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Affiliation(s)
- Zohreh Heydari
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran.,Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Emadoddin Moudi
- Department of Urology, Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Iran.,Cancer Research Center, Health Research Institute, Babol Univbersity of Medical Sciences, Babol, Iran
| | - Farzin Sadeghi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mahmoud Hajiahmadi
- Department of Epidemiology, Babol University of Medical Sciences, Babol, Iran
| | - Setareh Rezatabar
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Nahid Neamati
- Department of Clinical Biochemistry, Babol University of Medical Sciences, Babol, Iran
| | - Hadi Parsian
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
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Huang W, Gao S, Liang WB, Li Y, Yuan R, Xiao DR. In situ growth of metal-organic layer on ultrathin Ti3C2T MXene nanosheet boosting fast electron/ion transport for electrochemiluminescence enhancement. Biosens Bioelectron 2022; 220:114886. [DOI: 10.1016/j.bios.2022.114886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/30/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022]
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Ullah H, Tian Y, Arbab S, Li K, Khan MIU, Rahman SU, Qadeer A, Muhammad N, Suleman, Hassan IU. Circulatory microRNAs in helminthiases: Potent as diagnostics biomarker, its potential role and limitations. Front Vet Sci 2022; 9:1018872. [PMID: 36387413 PMCID: PMC9650547 DOI: 10.3389/fvets.2022.1018872] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/30/2022] [Indexed: 08/08/2023] Open
Abstract
Infections caused by helminths are responsible for severe public health problems and economic burden on continental scale. Well-timed and precise diagnosis of helminth infections is critical for taking by appropriate approaches for pathogen control. Circulating miRNAs are stable diagnostic tool for different diseases found in a variety of body fluid. As diagnostic biomarkers in infectious diseases, miRNAs detection in body fluids of helminth infected hosts is growing promptly. Uncovering miRNAs is a relatively new tool, used for early-stage detection of helminth infection from experimental or non-invasive clinical samples. miRNAs can be detected in body fluids such as serum, saliva, urine, and tissues of helminth infected host, mainly blood offering important benefits for diagnosis accurately. In this review, we discuss different characteristics of helminth parasite-derived circulating and EV miRNAs, supporting its potential uses in for helminth diagnosis and treatment efficiency.
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Affiliation(s)
- Hanif Ullah
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Yali Tian
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Safia Arbab
- Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Ka Li
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Muhammad Inayat Ullah Khan
- State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan, China
| | - Sajid Ur Rahman
- Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Abdul Qadeer
- Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
| | - Nehaz Muhammad
- Department of Zoology, University of Swabi, Swabi, Pakistan
| | - Suleman
- Department of Zoology, University of Swabi, Swabi, Pakistan
| | - Inam Ul Hassan
- Department of Microbiology, Hazara University Manshera, Manshera, Pakistan
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36
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Su F, Gao Z, Liu Y, Zhou G, Gao W, Deng C, Liu Y, Zhang Y, Ma X, Wang Y, Guan L, Zhang Y, Liu B. Prioritizing key synergistic circulating microRNAs for the early diagnosis of biliary tract cancer. Front Oncol 2022; 12:968412. [PMID: 36276146 PMCID: PMC9582275 DOI: 10.3389/fonc.2022.968412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 09/20/2022] [Indexed: 11/13/2022] Open
Abstract
Biliary tract cancer (BTC) is a highly aggressive malignant tumor. Serum microRNAs (ser-miRNAs) serve as noninvasive biomarkers to identify high risk individuals, thereby facilitating the design of precision therapies. The study is to prioritize key synergistic ser-miRNAs for the diagnosis of early BTC. Sampling technology, significant analysis of microarrays, Pearson Correlation Coefficients, t-test, decision tree, and entropy weight were integrated to develop a global optimization algorithm of decision forest. The source code is available at https://github.com/SuFei-lab/GOADF.git. Four key synergistic ser-miRNAs were prioritized and the synergistic classification performance was better than the single miRNA’ s. In the internal feature evaluation dataset, the area under the receiver operating characteristic curve (AUC) for each single miRNA was 0.8413 (hsa-let-7c-5p), 0.7143 (hsa-miR-16-5p), 0.8571 (hsa-miR-17-5p), and 0.9365 (hsa-miR-26a-5p), respectively, whereas the synergistic AUC value increased to 1.0000. In the internal test dataset, the single AUC was 0.6500, 0.5125, 0.6750, and 0.7500, whereas the synergistic AUC increased to 0.8375. In the independent test dataset, the single AUC was 0.7280, 0.8313, 0.8957, and 0.8303, and the synergistic AUC was 0.9110 for discriminating between BTC patients and healthy controls. The AUC for discriminating BTC from pancreatic cancer was 0.9000. Hsa-miR-26a-5p was a predictor of prognosis, patients with high expression had shorter survival than those with low expression. In conclusion, hsa-let-7c-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-26a-5p may act as key synergistic biomarkers and provide important molecular mechanisms that contribute to pathogenesis of BTC.
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Affiliation(s)
- Fei Su
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Ziyu Gao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yueyang Liu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Guiqin Zhou
- Department of Immunology, Harbin Medical University, Harbin, China
| | - Wei Gao
- Laboratory of Medical Genetics, Harbin Medical University, Harbin, China
| | - Chao Deng
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yuyu Liu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yihao Zhang
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Xiaoyan Ma
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Yongxia Wang
- Department of Anatomy, Harbin Medical University, Harbin, China
| | - Lili Guan
- Department of Information Management, Shanghai Lixin University of Accounting and Finance, Shanghai, China
- *Correspondence: Baoquan Liu, ; Yafang Zhang, ; Lili Guan,
| | - Yafang Zhang
- Department of Anatomy, Harbin Medical University, Harbin, China
- *Correspondence: Baoquan Liu, ; Yafang Zhang, ; Lili Guan,
| | - Baoquan Liu
- Department of Anatomy, Harbin Medical University, Harbin, China
- Department of Modern Medicine and Pharmacy, University of Tibetan Medicine, Lhasa, China
- *Correspondence: Baoquan Liu, ; Yafang Zhang, ; Lili Guan,
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Mokhtari F, Kaboosi H, Mohebbi SR, Asadzadeh Aghdaei H, Zali MRZ. Evaluation of Circulating MicroRNA-222 in Patients with Chronic Hepatitis B virus Infection as a Potential Noninvasive Diagnostic Biomarker. IRANIAN JOURNAL OF MEDICAL MICROBIOLOGY 2022. [DOI: 10.30699/ijmm.16.6.543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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38
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Chavez‐Pineda OG, Rodriguez‐Moncayo R, Cedillo‐Alcantar DF, Guevara‐Pantoja PE, Amador‐Hernandez JU, Garcia‐Cordero JL. Microfluidic systems for the analysis of blood‐derived molecular biomarkers. Electrophoresis 2022; 43:1667-1700. [DOI: 10.1002/elps.202200067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 06/18/2022] [Accepted: 06/22/2022] [Indexed: 12/19/2022]
Affiliation(s)
- Oriana G. Chavez‐Pineda
- Laboratory of Microtechnologies Applied to Biomedicine (LMAB) Centro de Investigación y de Estudios Avanzados (Cinvestav) Monterrey Nuevo León Mexico
| | - Roberto Rodriguez‐Moncayo
- Laboratory of Microtechnologies Applied to Biomedicine (LMAB) Centro de Investigación y de Estudios Avanzados (Cinvestav) Monterrey Nuevo León Mexico
| | - Diana F. Cedillo‐Alcantar
- Laboratory of Microtechnologies Applied to Biomedicine (LMAB) Centro de Investigación y de Estudios Avanzados (Cinvestav) Monterrey Nuevo León Mexico
| | - Pablo E. Guevara‐Pantoja
- Laboratory of Microtechnologies Applied to Biomedicine (LMAB) Centro de Investigación y de Estudios Avanzados (Cinvestav) Monterrey Nuevo León Mexico
| | - Josue U. Amador‐Hernandez
- Laboratory of Microtechnologies Applied to Biomedicine (LMAB) Centro de Investigación y de Estudios Avanzados (Cinvestav) Monterrey Nuevo León Mexico
| | - Jose L. Garcia‐Cordero
- Laboratory of Microtechnologies Applied to Biomedicine (LMAB) Centro de Investigación y de Estudios Avanzados (Cinvestav) Monterrey Nuevo León Mexico
- Roche Institute for Translational Bioengineering (ITB) Roche Pharma Research and Early Development, Roche Innovation Center Basel Basel Switzerland
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Yurttaş NÖ, Eşkazan AE. Clinical Application of Biomarkers for Hematologic Malignancies. Biomark Med 2022. [DOI: 10.2174/9789815040463122010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Over the last decade, significant advancements have been made in the
molecular mechanisms, diagnostic methods, prognostication, and treatment options in
hematologic malignancies. As the treatment landscape continues to expand,
personalized treatment is much more important.
With the development of new technologies, more sensitive evaluation of residual
disease using flow cytometry and next generation sequencing is possible nowadays.
Although some conventional biomarkers preserve their significance, novel potential
biomarkers accurately detect the mutational landscape of different cancers, and also,
serve as prognostic and predictive biomarkers, which can be used in evaluating therapy
responses and relapses. It is likely that we will be able to offer a more targeted and
risk-adapted therapeutic approach to patients with hematologic malignancies guided by
these potential biomarkers. This chapter summarizes the biomarkers used (or proposed
to be used) in the diagnosis and/or monitoring of hematologic neoplasms.;
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Affiliation(s)
- Nurgül Özgür Yurttaş
- Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine,
Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ahmet Emre Eşkazan
- Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine,
Istanbul University-Cerrahpasa, Istanbul, Turkey
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Maldonato BJ, Vergara AG, Yadav J, Glass SM, Paragas EM, Li D, Lazarus P, McClay JL, Ning B, Daly AK, Russell LE. Epigenetics in drug disposition & drug therapy: symposium report of the 24 th North American meeting of the International Society for the Study of Xenobiotics (ISSX). Drug Metab Rev 2022; 54:318-330. [PMID: 35876105 PMCID: PMC9970013 DOI: 10.1080/03602532.2022.2101662] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/10/2022] [Indexed: 11/03/2022]
Abstract
The 24th North American International Society for the Study of Xenobiotics (ISSX) meeting, held virtually from September 13 to 17, 2021, embraced the theme of "Broadening Our Horizons." This reinforces a key mission of ISSX: striving to share innovative science related to drug discovery and development. Session speakers and the ISSX New Investigators Group, which supports the scientific and professional development of student and early career ISSX members, elected to highlight the scientific content presented during the captivating session titled, "Epigenetics in Drug Disposition & Drug Therapy." The impact genetic variation has on drug response is well established; however, this session underscored the importance of investigating the role of epigenetics in drug disposition and drug discovery. Session speakers, Drs. Ning, McClay, and Lazarus, detailed mechanisms by which epigenetic players including long non-coding RNA (lncRNAs), microRNA (miRNAs), DNA methylation, and histone acetylation can alter the expression of genes involved in pharmacokinetics, pharmacodynamics, and toxicity. Dr. Ning detailed current knowledge about miRNAs and lncRNAs and the mechanisms by which they can affect the expression of drug metabolizing enzymes (DMEs) and nuclear receptors. Dr. Lazarus discussed the potential role of miRNAs on UDP-glucuronosyltransferase (UGT) expression and activity. Dr. McClay provided evidence that aging alters methylation and acetylation of DMEs in the liver, affecting gene expression and activity. These topics, compiled by the symposium organizers, presenters, and the ISSX New Investigators Group, are herein discussed, along with exciting future perspectives for epigenetics in drug disposition and drug discovery research.
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Affiliation(s)
- Benjamin J Maldonato
- Department of Nonclinical Development and Clinical Pharmacology, Revolution Medicines, Inc, Redwood City, CA, United States
| | - Ana G Vergara
- Department of ADME & Discovery Toxicology, Merck & Co., Inc, Rahway, NJ, United States
| | - Jaydeep Yadav
- Department of ADME & Discovery Toxicology, Merck & Co., Inc, Rahway, NJ, United States
| | - Sarah M Glass
- Janssen Research & Development, San Diego, CA, United States
| | | | - Dongying Li
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, United States
| | - Philip Lazarus
- Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, United States
| | - Joseph L McClay
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, United States
| | - Baitang Ning
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, United States
| | - Ann K Daly
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Laura E Russell
- Drug Metabolism and Pharmacokinetics, AbbVie Inc, North Chicago, Illinois, United States
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Target-Responsive Template Structure Switching-Mediated Exponential Rolling Circle Amplification for the Direct and Sensitive Detection of MicroRNA. BIOCHIP JOURNAL 2022. [DOI: 10.1007/s13206-022-00071-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
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Mitchell MI, Ma J, Carter CL, Loudig O. Circulating Exosome Cargoes Contain Functionally Diverse Cancer Biomarkers: From Biogenesis and Function to Purification and Potential Translational Utility. Cancers (Basel) 2022; 14:3350. [PMID: 35884411 PMCID: PMC9318395 DOI: 10.3390/cancers14143350] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/01/2022] [Accepted: 07/07/2022] [Indexed: 12/12/2022] Open
Abstract
Although diagnostic and therapeutic treatments of cancer have tremendously improved over the past two decades, the indolent nature of its symptoms has made early detection challenging. Thus, inter-disciplinary (genomic, transcriptomic, proteomic, and lipidomic) research efforts have been focused on the non-invasive identification of unique "silver bullet" cancer biomarkers for the design of ultra-sensitive molecular diagnostic assays. Circulating tumor biomarkers, such as CTCs and ctDNAs, which are released by tumors in the circulation, have already demonstrated their clinical utility for the non-invasive detection of certain solid tumors. Considering that exosomes are actively produced by all cells, including tumor cells, and can be found in the circulation, they have been extensively assessed for their potential as a source of circulating cell-specific biomarkers. Exosomes are particularly appealing because they represent a stable and encapsulated reservoir of active biological compounds that may be useful for the non-invasive detection of cancer. T biogenesis of these extracellular vesicles is profoundly altered during carcinogenesis, but because they harbor unique or uniquely combined surface proteins, cancer biomarker studies have been focused on their purification from biofluids, for the analysis of their RNA, DNA, protein, and lipid cargoes. In this review, we evaluate the biogenesis of normal and cancer exosomes, provide extensive information on the state of the art, the current purification methods, and the technologies employed for genomic, transcriptomic, proteomic, and lipidomic evaluation of their cargoes. Our thorough examination of the literature highlights the current limitations and promising future of exosomes as a liquid biopsy for the identification of circulating tumor biomarkers.
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Affiliation(s)
- Megan I Mitchell
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
| | - Junfeng Ma
- Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
| | - Claire L Carter
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
| | - Olivier Loudig
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
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Starlard-Davenport A, Gu Q, Pace BS. Targeting Genetic Modifiers of HBG Gene Expression in Sickle Cell Disease: The miRNA Option. Mol Diagn Ther 2022; 26:497-509. [PMID: 35553407 PMCID: PMC9098152 DOI: 10.1007/s40291-022-00589-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2022] [Indexed: 12/14/2022]
Abstract
Sickle cell disease (SCD) is one of the most common inherited hemoglobinopathy disorders that affects millions of people worldwide. Reactivation of HBG (HBG1, HBG2) gene expression and induction of fetal hemoglobin (HbF) is an important therapeutic strategy for ameliorating the clinical symptoms and severity of SCD. Hydroxyurea is the only US FDA-approved drug with proven efficacy to induce HbF in SCD patients, yet serious complications have been associated with its use. Over the last three decades, numerous additional pharmacological agents that reactivate HBG transcription in vitro have been investigated, but few have proceeded to FDA approval, with the exception of arginine butyrate and decitabine; however, neither drug met the requirements for routine clinical use due to difficulties with oral delivery and inability to achieve therapeutic levels. Thus, novel approaches that produce sufficient efficacy, specificity, and sustainable HbF induction with low adverse effects are desirable. More recently, microRNAs (miRNAs) have gained attention for their diagnostic and therapeutic potential to treat various diseases ranging from cancer to Alzheimer’s disease via targeting oncogenes and their gene products. Thus, it is plausible that miRNAs that target HBG regulatory genes may be useful for inducing HbF as a treatment for SCD. Our laboratory and others have documented the association of miRNAs with HBG activation or suppression via silencing transcriptional repressors and activators, respectively, of HBG expression. Herein, we review progress made in understanding molecular mechanisms of miRNA-mediated HBG regulation and discuss the extent to which molecular targets of HBG might be suitable prospects for development of SCD clinical therapy. Lastly, we discuss challenges with the application of miRNA delivery in vivo and provide potential strategies for overcoming barriers in the future.
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Affiliation(s)
- Athena Starlard-Davenport
- College of Medicine, Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
| | - Qingqing Gu
- College of Medicine, Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.,Department of Cardiology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China
| | - Betty S Pace
- Department of Pediatrics, Division of Hematology/Oncology, Augusta University, Augusta, GA, USA.,Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA, USA
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Sargazi S, Mukhtar M, Rahdar A, Bilal M, Barani M, Díez-Pascual AM, Behzadmehr R, Pandey S. Opportunities and challenges of using high-sensitivity nanobiosensors to detect long noncoding RNAs: A preliminary review. Int J Biol Macromol 2022; 205:304-315. [PMID: 35182562 DOI: 10.1016/j.ijbiomac.2022.02.082] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 12/17/2022]
Abstract
The two types ofncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are responsible for several biological processes within cells, such as the immune responses, cell growth and invasion, and regulation of the cell cycle. Rapidly expanding class of ncRNAs, lncRNAsinteract with other molecules to form chromatin-remodeling complexes. These potential hallmarks of diseases contribute to transcriptional and post-transcriptional regulation of several genes, possibly via cross-talk with other RNAs. Aberrant expression of lncRNAshas drawn increasing attention to the pathophysiology of different diseases, includingcancer and cardiovasculardiseases. Unfortunately, circulating lncRNAs are presented in the bloodstream at very low levels, making sensitive detection difficult. Currently, there are few methods for detecting these ncRNAs from which quantitative real-time-polymerase chain reaction (qRT-PCR) is the most routinely used technique. These techniqueslack sensitivity for intracellular detection of lncRNAs. Moreover, they are tedious and require a large sample size. Currently, nanotechnology has taken over the diagnostic field because of the tunable properties and modification opportunities. Furthermore, these conventional techniques can be merged with nanotechnology to improve detection sensitivity.This review highlights some of the most recent findings on nanotechnology-based methods and possible obstacles intheir application for moreaccurate sensing of lncRNAs.
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Affiliation(s)
- Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan 9816743463, Iran
| | - Mahwash Mukhtar
- Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Eötvösutca 6, Szeged 6720, Hungary
| | - Abbas Rahdar
- Department of Physics, Faculty of Science, University of Zabol, 538-98615 Zabol, Iran.
| | - Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China
| | - Mahmood Barani
- Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman 7616913555, Iran
| | - Ana M Díez-Pascual
- Universidad de Alcalá, Facultad de Ciencias, Departamento de Química Analítica, Química Física e Ingeniería Química, Ctra. Madrid-Barcelona, Km. 33.6, 28805 Alcalá de Henares, Madrid, Spain
| | - Razieh Behzadmehr
- Department of Radiology, Zabol university of medical sciences, Zabol, Iran
| | - Sadanand Pandey
- Department of Chemistry, College of Natural Science, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, South Korea.
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miR-1290 modulates the radioresistance of triple-negative breast cancer by targeting NLRP3-mediated pyroptosis. Clin Transl Oncol 2022; 24:1764-1775. [PMID: 35471684 DOI: 10.1007/s12094-022-02831-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 03/30/2022] [Indexed: 12/19/2022]
Abstract
PURPOSE To explore the roles and underlying mechanisms of miR-1290 in determining the sensitivity of triple-negative breast cancer (TNBC) to radiation therapy. METHODS ELISA was performed to detect the levels of IL-18 and IL-1β in radiosensitive cells and serum samples. The level of miR-1290 in radiosensitive cells and tissues was assessed by qRT-PCR assay. A luciferase reporter assay was performed to confirm NLRP3 as the target of miR-1290. Functionally, the roles of miR-1290 in TNBC radioresistance were analyzed by transfection of either miR-1290 mimic or miR-1290 inhibitor. Moreover, the involvement of the miR-1290/NLRP3 axis in TNBC radioresistance was analyzed by experiments with a miR-1290 mimic and NLRP3 overexpression. MTT and colony formation assays were used to detect radiation-induced cell viability and proliferation. qRT-PCR and western blot assays were used to detect pyroptosis markers (NLRP3, ACS and caspase-1). RESULTS The results showed that radioresistance in TNBC cells was associated with a reduction in pyroptosis. miR-1290 expression was increased in radioresistant cells, and it had higher expression levels in the radioresistant tumor tissues of TNBC patients compared to the radiosensitive samples. The miR-1290 mimic suppressed radiation-induced pyroptosis and reduced the radiosensitivity of TNBC cells. Moreover, we found that NLRP3 was a potential target of miR-1290. Overexpression of NLRP3 partly reversed the effects of miR-1290 on pyroptosis and radioresistance. The mouse models showed that miR-1290 suppressed tumor size, tumor weight and pyroptosis. CONCLUSIONS miR-1290/NLRP3-mediated pyroptosis may play an important role in determining radioresistance in TNBC and serve as a novel therapeutic option.
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Cornejo MA, Linz TH. Multiplexed miRNA Quantitation Using Injectionless Microfluidic Thermal Gel Electrophoresis. Anal Chem 2022; 94:5674-5681. [PMID: 35349277 DOI: 10.1021/acs.analchem.2c00356] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
MicroRNAs (miRNAs) are a class of biomolecules that have high clinical and pharmaceutical significance because of their ability to regulate protein expression. Better methods are needed to quantify target miRNAs, but their similar sequence lengths and low concentrations in biomedical samples impede analysis. This report aimed to develop a simple, rapid method to directly quantify multiple miRNAs using microfluidic thermal gel electrophoresis (TGE). Fluorescent probes were designed complementarily in sequence to four target miRNAs that also contained variable DNA overhangs to alter their electrophoretic mobilities. Samples and probes were directly added into thermal gel and loaded throughout a microchannel. Applying voltage resulted in an inline preconcentration and separation of the miRNAs that did not require a sample injection nor user intervention to switch between modes. Baseline resolution was achieved between four double-stranded miRNA-probe hybrids and four excess single-stranded probes. Analytical performance was then improved by designing an innovative microfluidic device with a tapered channel geometry. This device exhibited superior detection limits and separation resolution compared to standard channel devices without increasing the complexity of microfabrication or device operation. A proof-of-concept demonstration was then performed, showing that target miRNAs could be detected from cell extracts. These results demonstrate that TGE provides a simple, inexpensive means of conducting multiplexed miRNA measurements, with the potential for automation to facilitate future clinical and pharmaceutical analyses.
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Affiliation(s)
- Mario A Cornejo
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States
| | - Thomas H Linz
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States
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47
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Falco M, Tammaro C, Takeuchi T, Cossu AM, Scafuro G, Zappavigna S, Itro A, Addeo R, Scrima M, Lombardi A, Ricciardiello F, Irace C, Caraglia M, Misso G. Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem. Cancers (Basel) 2022; 14:1716. [PMID: 35406495 PMCID: PMC8997012 DOI: 10.3390/cancers14071716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/01/2022] [Accepted: 03/24/2022] [Indexed: 11/19/2022] Open
Abstract
Laryngeal squamous cell cancer (LSCC) accounts for almost 25-30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising as they circulate in all the biological fluids allowing liquid biopsy determination, as well as due to their quick and characteristic modulation useful for non-invasive detection and monitoring of cancer. Other critical aspects are related to recent progress in circulating tumor cells and DNA detection, in metastatic status and chemo-refractoriness prediction, and in the functional interaction of LSCC with chronic inflammation and innate immunity. We review all these aspects taking into account the progress of the technologies in the field of next generation sequencing.
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Affiliation(s)
- Michela Falco
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Chiara Tammaro
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Takashi Takeuchi
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
- Molecular Diagnostics Division, Wakunaga Pharmaceutical Co., Ltd., Hiroshima 739-1195, Japan
| | - Alessia Maria Cossu
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Giuseppe Scafuro
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Silvia Zappavigna
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | - Annalisa Itro
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy;
| | - Raffaele Addeo
- Oncology Operative Unit, Hospital of Frattamaggiore, ASLNA-2NORD, 80020 Naples, Italy;
| | - Marianna Scrima
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Angela Lombardi
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
| | | | - Carlo Irace
- Department of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Michele Caraglia
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
- Laboratory of Molecular and Precision Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy;
| | - Gabriella Misso
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.F.); (C.T.); (T.T.); (A.M.C.); (G.S.); (S.Z.); (A.L.); (M.C.)
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Bagheri M, Sarabi PZ, Mondanizadeh M. The role of miRNAs as a big master regulator of signaling pathways involved in lymphoblastic leukemia. J Cell Physiol 2022; 237:2128-2139. [PMID: 35315068 DOI: 10.1002/jcp.30720] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/02/2022] [Accepted: 02/18/2022] [Indexed: 12/17/2022]
Abstract
MicroRNAs (miRNAs) belong to small noncoding RNAs, which have long attracted researchers' attention because of their potency in acting either as oncogenes or tumor-suppressors in cancers. acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are two known types of leukemia with high mortality rates in adults and children. On a molecular basis, various signaling pathways are active in both types, making researchers consider the potential role of miRNAs in activating or suppressing these pathways to further hinder cancer development. In this review, we summarized the potential miRNAs, especially circulating ones, involved in essential signaling pathways in the ALL and CLL patients which serve as biomarkers and valuable targets in the treatment fields.
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Affiliation(s)
- Malihe Bagheri
- Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Parisa Zia Sarabi
- Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Mahdieh Mondanizadeh
- Department of Biotechnology and Molecular Medicine, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
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Teoh SL, Das S. MicroRNAs in Various Body Fluids and its importance in Forensic Medicine. Mini Rev Med Chem 2022; 22:2332-2343. [PMID: 35240957 DOI: 10.2174/1389557522666220303141558] [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: 10/21/2021] [Revised: 12/17/2021] [Accepted: 01/21/2022] [Indexed: 11/22/2022]
Abstract
MicroRNAs (miRNAs) are a class of noncoding RNAs which regulate gene expression. miRNAs have tissue-specific expression and are also present in various extracellular body fluids, including blood, tears, semen, vaginal fluid and urine. Additionally, expression of miRNAs in body fluids is linked to various pathological diseases, including cancer and neurodegenerative diseases. Examination of body fluids is important in forensic medicine as they serve as a valuable form of evidence. Due to its stability, miRNA offers an advantage for body fluid identification, which can be detected even after several months or from compromised samples. Identification of unique miRNA profiles for different body fluids enable the identification of these body fluid. Furthermore, miRNAs profiling can be used to estimate post-mortem interval. Various biochemical and molecular methods have been used for identification of miRNAs have shown promising results. We discuss different miRNAs as specific biomarkers and their clinical importance regarding different pathological conditions, as well as their medico-legal importance.
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Affiliation(s)
- Seong Lin Teoh
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000, Kuala Lumpur, Malaysia
| | - Srijit Das
- Department of Human & Clinical Anatomy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat 123, Sultanate of Oman
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50
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Oskouie AA, Ahmadi MS, Taherkhani A. Identification of Prognostic Biomarkers in Papillary Thyroid Cancer and Developing Non-Invasive Diagnostic Models Through Integrated Bioinformatics Analysis. Microrna 2022; 11:73-87. [PMID: 35068400 DOI: 10.2174/2211536611666220124115445] [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: 08/30/2021] [Revised: 12/21/2021] [Accepted: 12/31/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Papillary thyroid cancer (PTC) is the most frequent subtype of thyroid carcinoma, mainly detected in patients with benign thyroid nodules (BTN). Due to the invasiveness of accurate diagnostic tests, there is a need to discover applicable biomarkers for PTC. So, in this study, we aimed to identify the genes associated with prognosis in PTC. Besides, we performed a machine learning tool to develop a non-invasive diagnostic approach for PTC. METHODS For the study purposes, the miRNA dataset GSE130512 was downloaded from the GEO database and then analyzed to identify the common differentially expressed miRNAs in patients with non-metastatic PTC (nm-PTC)/metastatic PTC (m-PTC) compared with BTNs. The SVM was also applied to differentiate patients with PTC from those patients with BTN using the common DEMs. A protein-protein interaction network was also constructed based on the targets of the common DEMs. Next, functional analysis was performed, the hub genes were determined, and survival analysis was then executed. RESULTS A total of three common miRNAs were found to be differentially expressed among patients with nm-PTC/m-PTC compared with BTNs. In addition, it was established that the autophagosome maturation, ciliary basal body-plasma membrane docking, antigen processing as ubiquitination & proteasome degradation, and class I MHC mediated antigen processing & presentation are associated with the pathogenesis of PTC. Furthermore, it was illustrated that RPS6KB1, CCNT1, SP1, and CHD4 might serve as new potential biomarkers for PTC prognosis. CONCLUSION RPS6KB1, CCNT1, SP1, and CHD4 may be considered new potential biomarkers used for prognostic aims in PTC. However, performing validation tests is inevitable in the future.
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Affiliation(s)
- Afsaneh Arefi Oskouie
- Department of Basic Science, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Saeed Ahmadi
- Department of Otorhinolaryngology, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir Taherkhani
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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