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Zhou X, Wu R, Tang G, Shen T, Li W. The predictive function of miR-122-5p and its action mechanism by regulating PKM2 in metabolic syndrome. BMC Endocr Disord 2025; 25:54. [PMID: 40011864 PMCID: PMC11866723 DOI: 10.1186/s12902-025-01888-2] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 02/21/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Obesity will cause metabolic syndrome (Mets) easily, and its pathogenesis is not completely clear. AIM To probe into the predictive value of miR-122-5p and its regulatory mechanism in Mets. METHOD The predictive effect of miR-122-5p on Mets was evaluated by constructing a Receiver Operating Characteristic (ROC) curve. The target genes of miR-122-5p were predicted using the ENCORI/starBase and TargetScanHuman databases, and pyruvate kinase M2 (PKM2), closely related to Mets, was screened by GO and KEGG analysis. The roles of miR-122-5p/PKM2 in insulin resistance (IR) were explored by treating the human normal liver cells (HLCs) with palmitic acid (PA) to induce the IR model. The effects of miR-122-5p/PKM2 on glucose metabolism (GM) of HLCs were evaluated by detecting the production of pyruvic acid, lactic acid, and ATP. RESULTS MiR-122-5p was highly expressed in obese people and Mets patients, and its predicted AUC for Mets was 0.876. In HLCs transfected with wild-type PKM2 luciferase vector (PKM2-wt), luciferase activity was attenuated by the miR-122-5p mimic and enhanced by its inhibitor. The expression of PKM2 was inhibited by the miR-122-5p mimic and up-regulated by its inhibitor. The miR-122-5p mimic enhanced PA-induced IR and inhibited the GM of HLCs, which were reversed by overexpression of PKM2. The miR-122-5p inhibitor exerted the opposite effects of its mimic, which were also reversed by silencing of PKM2. CONCLUSION MiR-122-5p, a risk factor for Mets, mediated the IR and abnormal glucose metabolism of HLCs by negatively regulating PKM2. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Xinglu Zhou
- Department of Endocrinology, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China
| | - Rui Wu
- Nursing Department, Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, 430065, China
| | - Guangfeng Tang
- Endocrinology Department, The Affiliated Chuzhou Hospital of Anhui Medical University, Chuzhou, 239000, China
| | - Tongtong Shen
- Cardiovascular Medicine, The Affiliated Chuzhou Hospital of Anhui Medical University, No. 369, West Drunken Weng Road, Nanqiao District, Chuzhou, Anhui, 239001, China.
| | - Wei Li
- Department of Endocrinology, Huanggang Central Hospital Affiliated to Yangtze University, No.6, Qi'an Avenue, Huangzhou District, Huanggang, Hubei Province, 438000, China.
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Matboli M, Hamady S, Saad M, Khaled R, Khaled A, Barakat EMF, Sayed SA, Agwa S, Youssef I. Innovative approaches to metabolic dysfunction-associated steatohepatitis diagnosis and stratification. Noncoding RNA Res 2025; 10:206-222. [PMID: 40248839 PMCID: PMC12004009 DOI: 10.1016/j.ncrna.2024.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 08/08/2024] [Accepted: 10/10/2024] [Indexed: 01/03/2025] Open
Abstract
The global rise in Metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic dysfunction-associated steatohepatitis (MASH) highlights the urgent necessity for noninvasive biomarkers to detect these conditions early. To address this, we endeavored to construct a diagnostic model for MASLD/MASH using a combination of bioinformatics, molecular/biochemical data, and machine learning techniques. Initially, bioinformatics analysis was employed to identify RNA molecules associated with MASLD/MASH pathogenesis and enriched in ferroptosis and exophagy. This analysis unveiled specific networks related to ferroptosis (GPX4, LPCAT3, ACSL4, miR-4266, and LINC00442) and exophagy (TSG101, HGS, SNF8, miR-4498, miR-5189-5p, and CTBP1-AS2). Subsequently, serum samples from 400 participants (151 healthy, 150 MASH, and 99 MASLD) underwent biochemical and molecular analysis, revealing significant dyslipidemia, impaired liver function, and disrupted glycemic indicators in MASLD/MASH patients compared to healthy controls. Molecular analysis indicated increased expression of LPCAT3, ACSL4, TSG101, HGS, and SNF8, alongside decreased GPX4 levels in MASH and MASLD patients compared to controls. The expression of epigenetic regulators from both networks (miR-4498, miR-5189-5p, miR-4266, LINC00442, and CTBP1-AS2) significantly differed among the studied groups. Finally, supervised machine learning models, including Neural Networks and Random Forest, were applied to molecular signatures and clinical/biochemical data. The Random Forest model exhibited superior performance, and molecular features effectively distinguished between the three studied groups. Clinical features, particularly BMI, consistently served as discriminatory factors, while biochemical features exhibited varying discriminant behavior across MASH, MASLD, and control groups. Our study underscores the significant potential of integrating diverse data types to enable early detection of MASLD/MASH, offering a promising approach for non-invasive diagnostic strategies.
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Affiliation(s)
- Marwa Matboli
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt
- Faculty of Oral & Dental Medicine, Misr International University, Qalyubiyya Governorate, Egypt
| | - Shaimaa Hamady
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
| | - Maha Saad
- Basic Sciences Department, Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt
| | - Radwa Khaled
- Basic Sciences Department, Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt
- Biotechnology/Biomolecular Chemistry Program, Faculty of Science, Cairo University & Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt
| | - Abdelrahman Khaled
- Bioinformatics Group, Center of Informatics Sciences (CIS), School of Information Technology and Computer Sciences, Nile University, Giza, Egypt
| | - Eman MF. Barakat
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sayed Ahmed Sayed
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - SaraH.A. Agwa
- Clinical Pathology and Molecular Genomics Unit, Medical Ain Shams Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, 11382, Egypt
| | - Ibrahim Youssef
- Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University, Egypt
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Tayeb BA, Osman AA, Njangiru IK. Liquid biopsy biomarkers in breast cancer: An overview of systematic reviews. Clin Chim Acta 2025; 566:120063. [PMID: 39615734 DOI: 10.1016/j.cca.2024.120063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 12/11/2024]
Abstract
Breast cancer (BC) is the leading type of cancer affecting women globally and remains a significant cause of death. The diagnostic accuracy of liquid biopsy (LB) in the diagnosis of BC has not been well established. This overview synthesizes and critically evaluates the diagnostic test accuracy (DTA) of LB biomarkers in individuals with BC. Of 433 systematic reviews, eleven were included, assessing Fourier transform infrared (FTIR) spectroscopy, circulating tumor cells (CTCs), cell-free DNA (cfDNA), and microRNAs (miRNAs). The overall methodological quality of most of the reviews included was rated as critically low (n = 9, 81.8 %), and the remaining reviews were ranked as low and moderate. Key findings include CTCs with moderate sensitivity (0.50, 95 % confidence interval (CI) 0.48-0.52) and high specificity (0.93, 95 % CI: 0.92-0.95) with moderate certainty; cfDNA assays with high sensitivity (0.71-0.86) and specificity (0.88) with high certainty; FTIR assays with high sensitivity (0.97, 95 % CI: 0.94-0.96) and specificity (0.92, 95 % CI: 0.88-0.95) but low certainty. The miRNAs showed moderate to high sensitivity, while miR-21 had high specificity. Our overview indicates that identified liquid biopsies could serve as valuable tools for the diagnosis of breast cancer.
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Affiliation(s)
- Bizhar Ahmed Tayeb
- Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged 6720, Hungary.
| | - Alaa Am Osman
- Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged 6720, Hungary; Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, University of Gezira, Wad Madani, P.O. Box: 20, Sudan
| | - Isaac Kinyua Njangiru
- Institute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged 6720, Hungary; Department of Chemistry and Biochemistry, School of Science and Applied Technology, Laikipia University, Nyahururu, P.O. Box, 1100-20300, Kenya
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Liao Q, Fu X, Zhuo L, Chen H. An efficient model for predicting human diseases through miRNA based on multiple-types of contrastive learning. Front Microbiol 2023; 14:1325001. [PMID: 38163075 PMCID: PMC10755968 DOI: 10.3389/fmicb.2023.1325001] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 11/16/2023] [Indexed: 01/03/2024] Open
Abstract
Multiple studies have demonstrated that microRNA (miRNA) can be deeply involved in the regulatory mechanism of human microbiota, thereby inducing disease. Developing effective methods to infer potential associations between microRNAs (miRNAs) and diseases can aid early diagnosis and treatment. Recent methods utilize machine learning or deep learning to predict miRNA-disease associations (MDAs), achieving state-of-the-art performance. However, the problem of sparse neighborhoods of nodes due to lack of data has not been well solved. To this end, we propose a new model named MTCL-MDA, which integrates multiple-types of contrastive learning strategies into a graph collaborative filtering model to predict potential MDAs. The model adopts a contrastive learning strategy based on topology, which alleviates the damage to model performance caused by sparse neighborhoods. In addition, the model also adopts a semantic-based contrastive learning strategy, which not only reduces the impact of noise introduced by topology-based contrastive learning, but also enhances the semantic information of nodes. Experimental results show that our model outperforms existing models on all evaluation metrics. Case analysis shows that our model can more accurately identify potential MDA, which is of great significance for the screening and diagnosis of real-life diseases. Our data and code are publicly available at: https://github.com/Lqingquan/MTCL-MDA.
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Affiliation(s)
- Qingquan Liao
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Xiangzheng Fu
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
| | - Linlin Zhuo
- School of Data Science and Artificial Intelligence, Wenzhou University of Technology, Wenzhou, China
| | - Hao Chen
- College of Computer Science and Electronic Engineering, Hunan University, Changsha, China
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5
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Koi Y, Yamamoto Y, Fukunaga S, Kajitani K, Ohara M, Daimaru Y, Tahara H, Tamada R. Assessment of the expression of microRNAs‑221‑3p, ‑146a‑5p, ‑16‑5p and BCL2 in oncocytic carcinoma of the breast: A case report. Oncol Lett 2023; 26:535. [PMID: 38020289 PMCID: PMC10655050 DOI: 10.3892/ol.2023.14123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 09/06/2023] [Indexed: 12/01/2023] Open
Abstract
Oncocytic carcinoma of the breast is rare and its molecular profiles remain poorly understood. MicroRNAs (miRNAs/miRs) have been identified as contributors to carcinogenesis at the post-transcriptional level; thus, an aberrant expression of miRNAs has attracted attention as a potential biomarker of numerous diseases, including cancer. The present study reports the case of a 76-year-old woman diagnosed with oncocytic carcinoma of the breast. Considering the distinctive feature of oncocytic carcinoma of the breast, which is the presence of granular eosinophilic cytoplasm containing numerous mitochondria, the present study hypothesized that the expression of mitochondria-related miRNAs could be altered in oncocytic carcinomas. Aberrant expression levels of the miRNAs previously reported as mitochondria-related miRNAs, such as miR-221-3p, -146a-5p and -16-5p, were revealed in tissue from specimens of oncocytic carcinoma of the breast, compared with that of a more typical type of invasive ductal carcinoma of the breast. The present study highlights the changes in miRNA expression in oncocytic carcinoma of the breast, suggesting its potential as a biomarker for diagnosis.
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Affiliation(s)
- Yumiko Koi
- Department of Breast Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka 811-1395, Japan
- Department of Breast Surgery, Japan Agricultural Co-operatives Hiroshima General Hospital, Hatsukaichi, Hiroshima 738-8503, Japan
| | - Yuki Yamamoto
- Department of Cellular and Molecular Biology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8553, Japan
| | - Saori Fukunaga
- Department of Cellular and Molecular Biology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8553, Japan
| | - Keiko Kajitani
- Department of Breast Surgery, Japan Agricultural Co-operatives Hiroshima General Hospital, Hatsukaichi, Hiroshima 738-8503, Japan
| | - Masahiro Ohara
- Department of Breast Surgery, Japan Agricultural Co-operatives Hiroshima General Hospital, Hatsukaichi, Hiroshima 738-8503, Japan
| | - Yutaka Daimaru
- Section of Pathological Research and Laboratory, Japan Agricultural Co-operatives Hiroshima General Hospital, Hiroshima 738-8503, Japan
| | - Hidetoshi Tahara
- Department of Cellular and Molecular Biology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima 734-8553, Japan
| | - Ryuichiro Tamada
- Department of Surgery, Nishiki Hospital, Yamaguchi 741-0061, Japan
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Gil-Kulik P, Petniak A, Kluz N, Wallner G, Skoczylas T, Ciechański A, Kocki J. Influence of Clinical Factors on miR-3613-3p Expression in Colorectal Cancer. Int J Mol Sci 2023; 24:14023. [PMID: 37762323 PMCID: PMC10531160 DOI: 10.3390/ijms241814023] [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: 08/01/2023] [Revised: 09/07/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common cause of cancer-related death globally. Because of a tendency to be an asymptomatic primary tumor and therefore resulting in late detection, most CRC patients are diagnosed in the advanced stage. Several miRNAs have the potential to become novel noninvasive biomarkers measured as diagnostic and prognostic indicators of CRC to guide surgical therapies and promote the understanding of the carcinogenesis of CRC. Since the change of miR-3613-3p was associated with several types of cancer other than colorectal cancer, there is a lack of functional evidence and the results are inconsistent. We conducted a pilot microarray study in which we noted a decreased expression of miR-3613-3p in colorectal cancer cells, then we confirmed the expression of miR-3613-3p by qPCR on a group of 83 patients, including 65 patients with colorectal cancer, 5 with a benign tumor and 13 from the control group. We noted that in both malignant and benign tumors, miR-3613-3p is downgraded relative to the surrounding tissue. As a result of the study, we also observed colorectal tumor tissue and surrounding tissue in patients with colorectal cancer who received radiotherapy before surgery, which showed a significantly higher expression of miR-3613-3p compared to patients who did not receive radiotherapy. In addition, we noted that the tissue surrounding the tumor in patients with distant metastases showed a significantly higher expression of miR-3613-3p compared to patients without distant metastases. The increased expression of miR-3613-3p in patients after radiotherapy suggests the possibility of using this miR as a therapeutic target for CRC, but this requires confirmation in further studies.
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Affiliation(s)
- Paulina Gil-Kulik
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland; (N.K.); (J.K.)
| | - Alicja Petniak
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland; (N.K.); (J.K.)
| | - Natalia Kluz
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland; (N.K.); (J.K.)
| | - Grzegorz Wallner
- II Chair and Department of General and Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, 16 Staszica Str., 20-081 Lublin, Poland; (G.W.); (T.S.); (A.C.)
| | - Tomasz Skoczylas
- II Chair and Department of General and Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, 16 Staszica Str., 20-081 Lublin, Poland; (G.W.); (T.S.); (A.C.)
| | - Aleksander Ciechański
- II Chair and Department of General and Gastrointestinal Surgery and Surgical Oncology of the Alimentary Tract, 16 Staszica Str., 20-081 Lublin, Poland; (G.W.); (T.S.); (A.C.)
| | - Janusz Kocki
- Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str., 20-080 Lublin, Poland; (N.K.); (J.K.)
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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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Macvanin MT, Gluvic Z, Bajic V, Isenovic ER. Novel insights regarding the role of noncoding RNAs in diabetes. World J Diabetes 2023; 14:958-976. [PMID: 37547582 PMCID: PMC10401459 DOI: 10.4239/wjd.v14.i7.958] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 05/01/2023] [Accepted: 05/22/2023] [Indexed: 07/12/2023] Open
Abstract
Diabetes mellitus (DM) is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance, inadequate insulin secretion, or excessive glucagon secretion. In 2021, the global prevalence of diabetes is anticipated to be 10.7% (537 million people). Noncoding RNAs (ncRNAs) appear to have an important role in the initiation and progression of DM, according to a growing body of research. The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs. miRNAs are single-stranded, short (17-25 nucleotides), ncRNAs that influence gene expression at the post-transcriptional level. Because DM has reached epidemic proportions worldwide, it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently. miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation. In this review, we address the issue of the gradually expanding global prevalence of DM by presenting a complete and up-to-date synopsis of various regulatory miRNAs involved in these disorders. We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM. We examine and synthesize recent research that used novel, high-throughput technologies to uncover ncRNAs involved in DM, necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses.
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Affiliation(s)
- Mirjana T Macvanin
- Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Clinic for Internal Medicine, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade 11000, Serbia
| | - Vladan Bajic
- Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, Vinča Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11000, Serbia
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Twenty Novel MicroRNAs in the Aqueous Humor of Pseudoexfoliation Glaucoma Patients. Cells 2023; 12:cells12050737. [PMID: 36899874 PMCID: PMC10000531 DOI: 10.3390/cells12050737] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 02/22/2023] [Indexed: 03/02/2023] Open
Abstract
The microRNAs (miRNAs) are short non-coding RNAs (19-25 nt) that regulate the level of gene expression at the post-transcriptional stage. Altered miRNAs expression can lead to the development of various diseases, e.g., pseudoexfoliation glaucoma (PEXG). In this study, we assessed the levels of miRNA expression in the aqueous humor of PEXG patients using the expression microarray method. Twenty new miRNA molecules have been selected as having the potential to be associated with the development or progression of PEXG. Ten miRNAs were downregulated in PEXG (hsa-miR-95-5p, hsa-miR-515-3p, hsa-mir-802, hsa-miR-1205, hsa-miR-3660, hsa-mir-3683, hsa -mir-3936, hsa-miR-4774-5p, hsa-miR-6509-3p, hsa-miR-7843-3p) and ten miRNAs were upregulated in PEXG (hsa-miR-202 -3p, hsa-miR-3622a-3p, hsa-mir-4329, hsa-miR-4524a-3p, hsa-miR-4655-5p, hsa-mir-6071, hsa-mir-6723-5p, hsa-miR-6847-5p, hsa-miR-8074, and hsa-miR-8083). Functional analysis and enrichment analysis showed that the mechanisms that can be regulated by these miRNAs are: extracellular matrix (ECM) imbalance, cell apoptosis (possibly retinal ganglion cells (RGCs)), autophagy, and elevated calcium cation levels. Nevertheless, the exact molecular basis of PEXG is unknown and further research is required on this topic.
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Left Ventricular Hypertrophy and Ventricular Tachyarrhythmia: The Role of Biomarkers. Int J Mol Sci 2023; 24:ijms24043881. [PMID: 36835293 PMCID: PMC9958550 DOI: 10.3390/ijms24043881] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/08/2023] [Accepted: 02/14/2023] [Indexed: 02/17/2023] Open
Abstract
Left ventricular hypertrophy (LVH) refers to a complex rebuilding of the left ventricle that can gradually lead to serious complications-heart failure and life-threatening ventricular arrhythmias. LVH is defined as an increase in the size of the left ventricle (i.e., anatomically), therefore the basic diagnosis detecting the increase in the LV size is the domain of imaging methods such as echocardiography and cardiac magnetic resonance. However, to evaluate the functional status indicating the gradual deterioration of the left ventricular myocardium, additional methods are available approaching the complex process of hypertrophic remodeling. The novel molecular and genetic biomarkers provide insights on the underlying processes, representing a potential basis for targeted therapy. This review summarizes the spectrum of the main biomarkers employed in the LVH valuation.
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Ye R, Lin Q, Xiao W, Mao L, Zhang P, Zhou L, Wu X, Jiang N, Zhang X, Zhang Y, Ma D, Huang J, Wang X, Deng L. miR-150-5p in neutrophil-derived extracellular vesicles associated with sepsis-induced cardiomyopathy in septic patients. Cell Death Dis 2023; 9:19. [PMID: 36681676 PMCID: PMC9867758 DOI: 10.1038/s41420-023-01328-x] [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: 11/03/2022] [Revised: 01/08/2023] [Accepted: 01/11/2023] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Early diagnosis and potential therapeutic targets of sepsis-induced cardiomyopathy (SIC) remain challenges clinically. Circulating extracellular vesicles from immune cells carrying crucial injurious mediators, including miRNAs in sepsis. However, the impacts of neutrophil-derived extracellular vesicles and their miRNAs in the SIC development are unknown. OBJECTIVES The present study focused on the in-depth miRNA expression profiles of neutrophil-derived extracellular vesicles and explored the potential molecular biomarkers during the process of SIC. METHODS Neutrophil-derived extracellular vesicles were isolated from the blood samples in three sepsis patients with or without cardiomyopathy on day 1 and day 3 after ICU admission in comparison with three healthy controls. miRNAs were determined by RNA sequencing. The closely related differentially expressed miRNAs with SIC were further validated through qRT-PCR in the other cohorts of sepsis patients with (30 patients) or without cardiomyopathy (20 patients) and the association between miRNAs and the occurrence or disease severity of septic cardiomyopathy were stratified with logistic regression analysis. RESULTS Sixty-eight miRNAs from neutrophil-derived extracellular vesicles were changed significantly between healthy controls and without septic cardiomyopathy patients (61 miRNAs upregulated and seven downregulated). Thirty-eight miRNAs were differentially expressed in the septic cardiomyopathy patients. 27 common differentially expressed miRNAs were found in both groups with similar kinetics (23 miRNAs upregulated and four downregulated). The enriched cellular signaling pathway mediated by miRNAs from sepsis to septic cardiomyopathy was the HIF-1 signaling system modulated septic inflammation. Using multivariate logistic regression analysis, miR-150-5p coupled with NT-pro BNP, LVEF, and SOFA score (AUC = 0.941) were found to be the independent predictors of septic cardiomyopathy. CONCLUSION miRNAs derived from neutrophil-derived extracellular vesicles play an important role in septic disease severity development towards cardiomyopathy. miR-150-5p may be a predictor of sepsis severity development but warrants further study.
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Affiliation(s)
- Rongzong Ye
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Qiuyun Lin
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Wenkai Xiao
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Lixia Mao
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Pengfei Zhang
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Lingshan Zhou
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Xiaoxia Wu
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Nannan Jiang
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Xihe Zhang
- Doctoral Scientific Research Center, Lianjiang People’s Hospital, Zhanjiang, 524400 China ,grid.410560.60000 0004 1760 3078Affiliated Lianjiang People’s Hospital, Guangdong Medical University, Zhanjiang, 524400 China ,Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023 China
| | - Yinhua Zhang
- grid.31501.360000 0004 0470 5905Department of Physiology & Biomedical Sciences, Ischemic/hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 03080 Korea ,grid.459480.40000 0004 1758 0638University Hospital Research Centre, Yanbian University Hospital, Yanji, Jilin Province 133000 China
| | - Daqing Ma
- grid.7445.20000 0001 2113 8111Division of Anesthetics, Pain, Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, UK ,grid.439369.20000 0004 0392 0021Chelsea and Westminster, Hospital, London, UK
| | - Jiahao Huang
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
| | - Xiaoyan Wang
- Doctoral Scientific Research Center, Lianjiang People’s Hospital, Zhanjiang, 524400 China ,grid.410560.60000 0004 1760 3078Affiliated Lianjiang People’s Hospital, Guangdong Medical University, Zhanjiang, 524400 China ,Laboratory of Southern Marine Science and Engineering, Zhanjiang, 524023 China
| | - Liehua Deng
- grid.410560.60000 0004 1760 3078Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000 China
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Mc Cormack BA, González-Cantó E, Tomás-Pérez S, Aghababyan C, Marí-Alexandre J, Götte M, Gilabert-Estellés J. Special Issue "miRNAs in the Era of Personalized Medicine: From Biomarkers to Therapeutics 2.0". Int J Mol Sci 2023; 24:ijms24031951. [PMID: 36768275 PMCID: PMC9916445 DOI: 10.3390/ijms24031951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/09/2023] [Indexed: 01/20/2023] Open
Abstract
Personalized medicine has become a new paradigm in the management of a variety of diseases [...].
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Affiliation(s)
- Bárbara Andrea Mc Cormack
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain
| | - Eva González-Cantó
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain
| | - Sarai Tomás-Pérez
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain
| | - Cristina Aghababyan
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain
- Department of Obstetrics and Gynaecology, General University Hospital of Valencia Consortium, 46014 Valencia, Spain
| | - Josep Marí-Alexandre
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain
- Department of Pathology, General University Hospital of Valencia Consortium, 46014 Valencia, Spain
- Correspondence: (J.M.-A.); (M.G.)
| | - Martin Götte
- Research Laboratory, Department of Gynecology and Obstetrics, Münster University Hospital, 48149 Münster, Germany
- Correspondence: (J.M.-A.); (M.G.)
| | - Juan Gilabert-Estellés
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain
- Department of Obstetrics and Gynaecology, General University Hospital of Valencia Consortium, 46014 Valencia, Spain
- Department of Pediatrics, Obstetrics and Gynaecology, University of Valencia, 46010 Valencia, Spain
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13
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Aggio-Bruce R, Schumann U, Cioanca AV, Chen FK, McLenachan S, Heath Jeffery RC, Das S, Natoli R. Serum miRNA modulations indicate changes in retinal morphology. Front Mol Neurosci 2023; 16:1130249. [PMID: 36937046 PMCID: PMC10020626 DOI: 10.3389/fnmol.2023.1130249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
Background Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression. Methods Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated. Results Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients. Conclusion In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.
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Affiliation(s)
- Riemke Aggio-Bruce
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
- The School of Medicine and Psychology, Acton, ACT, Australia
| | - Ulrike Schumann
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
- The Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Adrian V. Cioanca
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
| | - Fred K. Chen
- Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia
- Lions Eye Institute, Perth, WA, Australia
- Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia
| | - Samuel McLenachan
- Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia
- Lions Eye Institute, Perth, WA, Australia
| | - Rachael C. Heath Jeffery
- Centre of Ophthalmology and Visual Science, The University of Western Australia, Perth, WA, Australia
- Lions Eye Institute, Perth, WA, Australia
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia
| | - Shannon Das
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
| | - Riccardo Natoli
- The John Curtin School of Medical Research, The Australian National University, Acton, ACT, Australia
- The School of Medicine and Psychology, Acton, ACT, Australia
- *Correspondence: Riccardo Natoli,
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14
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Haque SS. Biomarkers in the diagnosis of neurodegenerative diseases. RUDN JOURNAL OF MEDICINE 2022. [DOI: 10.22363/2313-0245-2022-26-4-431-440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Biomarkers are molecules that behave as of biological states. Ideally, they should have high sensitivity, specificity, and accuracy in reflecting the total disease burden. The review discusses the current status of biomarkers used in neurological disorders. Neurodegenerative diseases are a heterogeneous group disorders characterized by progressive loss of structure and function of the central nervous system or peripheral nervous system. The review discusses the main biomarkers that have predictive value for describing clinical etiology, pathophysiology, and intervention strategies. Preciseness and reliability are one of important requirement for good biomarker. As a result of the analysis of literature data, it was revealed that beta-amyloid, total tau protein and its phosphorylated forms are the first biochemical biomarkers of neurodegenerative diseases measured in cerebrospinal fluid, but these markers are dependent upon invasive lumbar puncture and therefore it’s a cumbersome process for patients. Among the various biomarkers of neurodegenerative diseases, special attention is paid to miRNAs. MicroRNAs, important biomarkers in many disease states, including neurodegenerative disorders, make them promising candidates that may lead to identify new therapeutic targets. Conclusions. Biomarkers of neurological disease are present optimal amount in the cerebrospinal fluid but they are also present in blood at low levels. The data obtained reveal the predictive value of molecular diagnostics of neurodegenerative disorders and the need for its wider use.
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Elgormus Y. Biomarkers and their Clinical Applications in Pediatrics. Biomark Med 2022. [DOI: 10.2174/9789815040463122010019] [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
Biomarker studies are becoming increasingly interesting for many fields of
medicine. The use of biomarkers in medicine is involved in detecting diseases and
supporting diagnosis and treatment decisions. New research and new discoveries on the
molecular basis of the disease show that there may be a number of promising new
biomarkers for use in daily clinical practice. Clinical trials in children lag behind adult
research both in quality and quantity. The number of biomarkers validated to optimize
pediatric patient management is limited. In the pathogenesis of many diseases, it should
not be extrapolated to the pediatric clinical setting, taking into account that biomarkers
that are effective in adults are clearly different in children and that ontogeny directly
affects disease development and therapeutic response in children. The search for ideal
biomarkers or markers that can make an early and definitive diagnosis in neonatal
sepsis is still ongoing. The ideal biomarker for pediatric diseases should be costeffective,
noninvasive, applicable to pediatric specific diseases, and its results should
correspond to age-related physiological changes. Lactate, troponin and B-type
natriuretic peptide are valuable biomarkers in the evaluation and management of
critically ill children with cardiac disease. Tumor markers in children are biochemical
substances used in the clinical treatment of pediatric tumors and to detect the presence
of cancer (regression or progression). In this chapter, current and brief information
about biomarkers and their clinical applications used in the diagnosis and monitoring of
pediatric diseases is presented.;
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Affiliation(s)
- Yusuf Elgormus
- Medicine Hospital,Department of Pediatric Health and Diseases,Department of Pediatric Health and Diseases, Medicine Hospital, Istanbul, Turkey,Istanbul,Turkey
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16
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Ohlstrom DJ, Sul C, Vohwinkel CU, Hernandez-Lagunas L, Karimpour-Fard A, Mourani PM, Carpenter TC, Nozik ES, Sucharov CC. Plasma microRNA and metabolic changes associated with pediatric acute respiratory distress syndrome: a prospective cohort study. Sci Rep 2022; 12:14560. [PMID: 36028738 PMCID: PMC9418138 DOI: 10.1038/s41598-022-15476-0] [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: 12/07/2021] [Accepted: 06/24/2022] [Indexed: 11/09/2022] Open
Abstract
Acute respiratory distress syndrome is a heterogeneous pathophysiological process responsible for significant morbidity and mortality in pediatric intensive care patients. Diagnosis is defined by clinical characteristics that identify the syndrome after development. Subphenotyping patients at risk of progression to ARDS could provide the opportunity for therapeutic intervention. microRNAs, non-coding RNAs stable in circulation, are a promising biomarker candidate. We conducted a single-center prospective cohort study to evaluate random forest classification of microarray-quantified circulating microRNAs in critically ill pediatric patients. We additionally selected a sub-cohort for parallel metabolomics profiling as a pilot study for concurrent use of miRNAs and metabolites as circulating biomarkers. In 35 patients (n = 21 acute respiratory distress, n = 14 control) 15 microRNAs were differentially expressed. Unsupervised random forest classification accurately grouped ARDS and control patients with an area under the curve of 0.762, which was improved to 0.839 when subset to only patients with bacterial infection. Nine metabolites were differentially abundant between acute respiratory distress and control patients (n = 4, both groups) and abundance was highly correlated with miRNA expression. Random forest classification of microRNAs differentiated critically ill pediatric patients who developed acute respiratory distress relative to those who do not. The differential expression of microRNAs and metabolites provides a strong foundation for further work to validate their use as a prognostic biomarker.
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Affiliation(s)
- Denis J Ohlstrom
- Developmental Lung Biology and Cardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Christina Sul
- Developmental Lung Biology and Cardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Division of Pediatric Critical Care, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Christine U Vohwinkel
- Developmental Lung Biology and Cardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Division of Pediatric Critical Care, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Laura Hernandez-Lagunas
- Developmental Lung Biology and Cardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Division of Pediatric Critical Care, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Anis Karimpour-Fard
- Department of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Peter M Mourani
- Division of Pediatric Critical Care, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Section of Pediatric Critical Care, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, AR, USA
| | - Todd C Carpenter
- Division of Pediatric Critical Care, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Eva S Nozik
- Developmental Lung Biology and Cardiovascular Pulmonary Research Laboratories, Departments of Pediatrics and Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Division of Pediatric Critical Care, Department of Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Carmen C Sucharov
- Division of Cardiology, Department of Medicine, University of Colorado, Anschutz Medical Campus, 12700 E 19th Ave B139, Aurora, CO, 80045, USA.
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Dudakovic A, Jerez S, Deosthale PJ, Denbeigh JM, Paradise CR, Gluscevic M, Zan P, Begun DL, Camilleri ET, Pichurin O, Khani F, Thaler R, Lian JB, Stein GS, Westendorf JJ, Plotkin LI, van Wijnen AJ. MicroRNA-101a enhances trabecular bone accrual in male mice. Sci Rep 2022; 12:13361. [PMID: 35922466 PMCID: PMC9349183 DOI: 10.1038/s41598-022-17579-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/27/2022] [Indexed: 11/09/2022] Open
Abstract
High-throughput microRNA sequencing was performed during differentiation of MC3T3-E1 osteoblasts to develop working hypotheses for specific microRNAs that control osteogenesis. The expression data show that miR-101a, which targets the mRNAs for the epigenetic enzyme Ezh2 and many other proteins, is highly upregulated during osteoblast differentiation and robustly expressed in mouse calvaria. Transient elevation of miR-101a suppresses Ezh2 levels, reduces tri-methylation of lysine 27 in histone 3 (H3K27me3; a heterochromatic mark catalyzed by Ezh2), and accelerates mineralization of MC3T3-E1 osteoblasts. We also examined skeletal phenotypes of an inducible miR-101a transgene under direct control of doxycycline administration. Experimental controls and mir-101a over-expressing mice were exposed to doxycycline in utero and postnatally (up to 8 weeks of age) to maximize penetrance of skeletal phenotypes. Male mice that over-express miR-101a have increased total body weight and longer femora. MicroCT analysis indicate that these mice have increased trabecular bone volume fraction, trabecular number and trabecular thickness with reduced trabecular spacing as compared to controls. Histomorphometric analysis demonstrates a significant reduction in osteoid volume to bone volume and osteoid surface to bone surface. Remarkably, while female mice also exhibit a significant increase in bone length, no significant changes were noted by microCT (trabecular bone parameters) and histomorphometry (osteoid parameters). Hence, miR-101a upregulation during osteoblast maturation and the concomitant reduction in Ezh2 mediated H3K27me3 levels may contribute to the enhanced trabecular bone parameters in male mice. However, the sex-specific effect of miR-101a indicates that more intricate epigenetic mechanisms mediate physiological control of bone formation and homeostasis.
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Affiliation(s)
- Amel Dudakovic
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
- Department of Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, USA.
| | - Sofia Jerez
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Padmini J Deosthale
- Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Janet M Denbeigh
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Christopher R Paradise
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA
- Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Martina Gluscevic
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Pengfei Zan
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Orthopedic Surgery, School of Medicine, Second Affiliated Hospital of Zhejiang University, Hangzhou, China
- Department of Orthopedic Surgery, School of Medicine, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China
| | - Dana L Begun
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Oksana Pichurin
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Farzaneh Khani
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Roman Thaler
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Jane B Lian
- Department of Biochemistry, University of Vermont, Burlington, VT, USA
| | - Gary S Stein
- Department of Biochemistry, University of Vermont, Burlington, VT, USA
| | - Jennifer J Westendorf
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Biochemistry & Molecular Biology, Mayo Clinic, Rochester, MN, USA
| | - Lilian I Plotkin
- Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
- Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA.
- Richard L Roudebush VA Medical Center, Indianapolis, IN, USA.
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Ye F, Feldman DR, Valentino A, So R, Bromberg M, Khan S, Funt SA, Sheinfeld J, Solit DB, Pessin MS, Peerschke EI. Analytical Validation and Performance Characteristics of Molecular Serum Biomarkers, miR-371a-3p and miR-372-3p, for Male Germ Cell Tumors, in a Clinical Laboratory Setting. J Mol Diagn 2022; 24:867-877. [PMID: 35934321 PMCID: PMC9379668 DOI: 10.1016/j.jmoldx.2022.04.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 03/17/2022] [Accepted: 04/22/2022] [Indexed: 12/12/2022] Open
Abstract
Detection of serum embryonic miRNAs miR-371a-3p and miR-372-3p has been proposed to aid in diagnosis, prognosis, and management of patients with testicular germ cell tumors (GCTs). This study describes the analytical validation and performance of a laboratory-developed test to detect these miRNA targets by stem loop real-time quantitative RT-PCR (RT-qPCR) in serum from patients with GCTs. The assay was standardized using an exogenous spike-in control of nonhuman miRNA from Caenorhabditis elegans (cel-miR-39-3p) to assess extraction efficiency, and an endogenous housekeeping miRNA, miR-30b-5p, to control for miRNA normalization. miRNA results were expressed as relative expression level, using the comparative threshold cycle method (2ΔΔCT). Analytical sensitivity of miR-371a-3p and miR-372-3p was 12.5 and 1.25 copies/μL, respectively. Clinical accuracy was evaluated using GCT patients with (n = 34) and without (n = 17) active disease. Positive/negative cutoffs and indeterminate findings were established on the basis of results from healthy volunteers (n = 25) and assay precision. miR-371a-3p and miR-372-3p exhibited a sensitivity of 81.8% and 87.5%, respectively, and a specificity of 100% and 94%, respectively, and an area under the receiver operating characteristic curve of 0.93 and 0.95, respectively. Taken together, RT-qPCR testing for serum miR-371a-3p and miR-372-3p represents a robust, sensitive, and specific clinical assay to aid in the clinical management of patients with GCT.
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Guio H, Aliaga-Tobar V, Galarza M, Pellon-Cardenas O, Capristano S, Gomez HL, Olivera M, Sanchez C, Maracaja-Coutinho V. Comparative Profiling of Circulating Exosomal Small RNAs Derived From Peruvian Patients With Tuberculosis and Pulmonary Adenocarcinoma. Front Cell Infect Microbiol 2022; 12:909837. [PMID: 35846752 PMCID: PMC9280157 DOI: 10.3389/fcimb.2022.909837] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/24/2022] [Indexed: 12/05/2022] Open
Abstract
Tuberculosis (TB) is one of the most fatal infectious diseases, caused by the aerobic bacteria Mycobacterium tuberculosis. It is estimated that one-third of the world’s population is infected with the latent (LTB) version of this disease, with only 5-10% of infected individuals developing its active (ATB) form. Pulmonary adenocarcinoma (PA) is the most common and diverse form of primary lung carcinoma. The simultaneous or sequential occurrence of TB and lung cancer in patients has been widely reported and is known to be an issue for diagnosis and surgical treatment. Raising evidence shows that patients cured of TB represent a group at risk for developing PA. In this work, using sRNA-sequencing, we evaluated the expression patterns of circulating small RNAs available in exosomes extracted from blood samples of Peruvian patients affected by latent tuberculosis, active tuberculosis, or pulmonary adenocarcinoma. Differential expression analysis revealed a set of 24 microRNAs perturbed in these diseases, revealing potential biomarker candidates for the Peruvian population. Most of these miRNAs are normally expressed in healthy lung tissue and are potential regulators of different shared and unique KEGG pathways related to cancers, infectious diseases, and immunology.
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Affiliation(s)
- Heinner Guio
- Laboratorio de Referencia Nacional de Biotecnología y Biología Molecular, Instituto Nacional de Salud, Lima, Peru
- Facultad de Ciencias de la Salud, Universidad de Huanuco, Huánuco, Peru
- *Correspondence: Heinner Guio, ; Vinicius Maracaja-Coutinho,
| | - Victor Aliaga-Tobar
- Advanced Center for Chronic Diseases - ACCDiS, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
- Centro de Modelamiento Molecular, Biofísica y Bioinformática - CMB, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
| | - Marco Galarza
- Laboratorio de Referencia Nacional de Biotecnología y Biología Molecular, Instituto Nacional de Salud, Lima, Peru
| | - Oscar Pellon-Cardenas
- Laboratorio de Referencia Nacional de Biotecnología y Biología Molecular, Instituto Nacional de Salud, Lima, Peru
- Department of Genetics, Human of Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, United States
| | - Silvia Capristano
- Laboratorio de Referencia Nacional de Biotecnología y Biología Molecular, Instituto Nacional de Salud, Lima, Peru
| | - Henry L. Gomez
- Departamento de Oncología Medica, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
| | - Mivael Olivera
- Departamento de Oncología Medica, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
| | - Cesar Sanchez
- Laboratorio de Referencia Nacional de Biotecnología y Biología Molecular, Instituto Nacional de Salud, Lima, Peru
| | - Vinicius Maracaja-Coutinho
- Advanced Center for Chronic Diseases - ACCDiS, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
- Centro de Modelamiento Molecular, Biofísica y Bioinformática - CMB, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
- Instituto Vandique, João Pessoa, Brazil
- *Correspondence: Heinner Guio, ; Vinicius Maracaja-Coutinho,
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Mohamed AA, Abo-Elmatty DM, Ezzat O, Mesbah NM, Ali NS, Abd El Fatah AS, Alsayed E, Hamada M, Hassnine AA, Abd-Elsalam S, Abdelghani A, Hassan MB, Fattah SA. Pro-Neurotensin as a Potential Novel Diagnostic Biomarker for Detection of Nonalcoholic Fatty Liver Disease. Diabetes Metab Syndr Obes 2022; 15:1935-1943. [PMID: 35769889 PMCID: PMC9234179 DOI: 10.2147/dmso.s365147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/27/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND AND AIMS Currently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case-control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases. METHODS Clinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs-122 and pro-neurotensin. RESULTS Compared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p<0.001) and at a cut-off ≥6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥108. CONCLUSION The circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH.
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Affiliation(s)
- Amal A Mohamed
- Biochemistry and Molecular Biology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Dina M Abo-Elmatty
- Biochemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Omnia Ezzat
- Biochemistry Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | - Noha M Mesbah
- Biochemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Nada S Ali
- Biochemistry Department, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | | | - Eman Alsayed
- Department of Clinical Pathology, Minia University Hospital, Minia, Egypt
| | - Mahmoud Hamada
- Internal Medicine Department, Faculty of Medicine, Benha University, Benha, Egypt
| | - Alshymaa A Hassnine
- Department of Gastroenterology and Tropical Medicine, Faculty of Medicine, Minia University, Minia, Egypt
| | | | - Ahmed Abdelghani
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Badr Hassan
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Shaimaa A Fattah
- Biochemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
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Liver Steatosis: A Marker of Metabolic Risk in Children. Int J Mol Sci 2022; 23:ijms23094822. [PMID: 35563210 PMCID: PMC9100068 DOI: 10.3390/ijms23094822] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/24/2022] [Accepted: 04/24/2022] [Indexed: 11/16/2022] Open
Abstract
Obesity is one of the greatest health challenges affecting children of all ages and ethnicities. Almost 19% of children and adolescents worldwide are overweight or obese, with an upward trend in the last decades. These reports imply an increased risk of fat accumulation in hepatic cells leading to a series of histological hepatic damages gathered under the acronym NAFLD (Non-Alcoholic Fatty Liver Disease). Due to the complex dynamics underlying this condition, it has been recently renamed as 'Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)', supporting the hypothesis that hepatic steatosis is a key component of the large group of clinical and laboratory abnormalities of Metabolic Syndrome (MetS). This review aims to share the latest scientific knowledge on MAFLD in children in an attempt to offer novel insights into the complex dynamics underlying this condition, focusing on the novel molecular aspects. Although there is still no treatment with a proven efficacy for this condition, starting from the molecular basis of the disease, MAFLD's therapeutic landscape is rapidly expanding, and different medications seem to act as modifiers of liver steatosis, inflammation, and fibrosis.
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22
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Alsop E, Meechoovet B, Kitchen R, Sweeney T, Beach TG, Serrano GE, Hutchins E, Ghiran I, Reiman R, Syring M, Hsieh M, Courtright-Lim A, Valkov N, Whitsett TG, Rakela J, Pockros P, Rozowsky J, Gallego J, Huentelman MJ, Shah R, Nakaji P, Kalani MYS, Laurent L, Das S, Van Keuren-Jensen K. A Novel Tissue Atlas and Online Tool for the Interrogation of Small RNA Expression in Human Tissues and Biofluids. Front Cell Dev Biol 2022; 10:804164. [PMID: 35317387 PMCID: PMC8934391 DOI: 10.3389/fcell.2022.804164] [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: 10/28/2021] [Accepted: 01/28/2022] [Indexed: 12/20/2022] Open
Abstract
One promising goal for utilizing the molecular information circulating in biofluids is the discovery of clinically useful biomarkers. Extracellular RNAs (exRNAs) are one of the most diverse classes of molecular cargo, easily assayed by sequencing and with expressions that rapidly change in response to subject status. Despite diverse exRNA cargo, most evaluations from biofluids have focused on small RNA sequencing and analysis, specifically on microRNAs (miRNAs). Another goal of characterizing circulating molecular information, is to correlate expression to injuries associated with specific tissues of origin. Biomarker candidates are often described as being specific, enriched in a particular tissue or associated with a disease process. Likewise, miRNA data is often reported to be specific, enriched for a tissue, without rigorous testing to support the claim. Here we provide a tissue atlas of small RNAs from 30 different tissues and three different blood cell types. We analyzed the tissues for enrichment of small RNA sequences and assessed their expression in biofluids: plasma, cerebrospinal fluid, urine, and saliva. We employed published data sets representing physiological (resting vs. acute exercise) and pathologic states (early- vs. late-stage liver fibrosis, and differential subtypes of stroke) to determine differential tissue-enriched small RNAs. We also developed an online tool that provides information about exRNA sequences found in different biofluids and tissues. The data can be used to better understand the various types of small RNA sequences in different tissues as well as their potential release into biofluids, which should help in the validation or design of biomarker studies.
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Affiliation(s)
- Eric Alsop
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Bessie Meechoovet
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Robert Kitchen
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Thadryan Sweeney
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Thomas G. Beach
- Banner Sun Health Research Institute, Sun City, AZ, United States
| | - Geidy E. Serrano
- Banner Sun Health Research Institute, Sun City, AZ, United States
| | - Elizabeth Hutchins
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Ionita Ghiran
- Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
| | - Rebecca Reiman
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Michael Syring
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Michael Hsieh
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Amanda Courtright-Lim
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Nedyalka Valkov
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Timothy G. Whitsett
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | | | - Paul Pockros
- Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA, United States
| | - Joel Rozowsky
- Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States
| | - Juan Gallego
- Institute for Behavioral Science, The Feinstein Institute for Medical Research, Manhasset, NY, United States
- Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, United States
- Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States
| | - Matthew J. Huentelman
- Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ, United States
| | - Ravi Shah
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
| | - Peter Nakaji
- Department of Neurosurgery, Banner Health, Phoenix, AZ, United States
| | - M. Yashar S. Kalani
- Department of Neurosurgery, St. John Medical Center, Tulsa, OK, United States
| | - Louise Laurent
- Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, San Diego, CA, United States
| | - Saumya Das
- Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
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23
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Dizon MLV, deRegnier RAO, Weiner SJ, Varner MW, Rouse DJ, Costantine MM, Wapner RJ, Thorp JM, Blackwell SC, Ayala NK, Saad AF, Caritis SN. Differential Gene Expression in Cord Blood of Infants Diagnosed with Cerebral Palsy: A Pilot Analysis of the Beneficial Effects of Antenatal Magnesium Cohort. Dev Neurosci 2022; 44:412-425. [PMID: 35705018 PMCID: PMC9474611 DOI: 10.1159/000525483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 06/08/2022] [Indexed: 02/01/2023] Open
Abstract
The Beneficial Effects of Antenatal Magnesium clinical trial was conducted between 1997 and 2007, and demonstrated a significant reduction in cerebral palsy (CP) in preterm infants who were exposed to peripartum magnesium sulfate (MgSO4). However, the mechanism by which MgSO4 confers neuroprotection remains incompletely understood. Cord blood samples from this study were interrogated during an era when next-generation sequencing was not widely accessible and few gene expression differences or biomarkers were identified between treatment groups. Our goal was to use bulk RNA deep sequencing to identify differentially expressed genes comparing the following four groups: newborns who ultimately developed CP treated with MgSO4 or placebo, and controls (newborns who ultimately did not develop CP) treated with MgSO4 or placebo. Those who died after birth were excluded. We found that MgSO4 upregulated expression of SCN5A only in the control group, with no change in gene expression in cord blood of newborns who ultimately developed CP. Regardless of MgSO4 exposure, expression of NPBWR1 and FTO was upregulated in cord blood of newborns who ultimately developed CP compared with controls. These data support that MgSO4 may not exert its neuroprotective effect through changes in gene expression. Moreover, NPBWR1 and FTO may be useful as biomarkers and may suggest new mechanistic pathways to pursue in understanding the pathogenesis of CP. The small number of cases ultimately available for this secondary analysis, with male predominance and mild CP phenotype, is a limitation of the study. In addition, differentially expressed genes were not validated by qRT-PCR.
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Affiliation(s)
- Maria L V Dizon
- The Department of Pediatrics, Northwestern University, Chicago, Illinois, USA
| | | | - Steven J Weiner
- The George Washington University Biostatistics Center, Washington, District of Columbia, USA
| | - Michael W Varner
- The Departments of Obstetrics and Gynecology of the University of Utah, Salt Lake City, Utah, USA
| | - Dwight J Rouse
- The Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Maged M Costantine
- The Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, USA
| | - Ronald J Wapner
- The Department of Obstetrics and Gynecology, Thomas Jefferson University and Drexel University, Philadelphia, Pennsylvania, USA
- The Department of Obstetrics and Gynecology, Columbia University, New York, New York, USA
| | - John M Thorp
- The Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Sean C Blackwell
- University of Texas Health Science Center at Houston-Children's Memorial Hermann Hospital, Houston, Texas, USA
| | - Nina K Ayala
- The Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island, USA
| | - Antonio F Saad
- The Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USA
| | - Steve N Caritis
- The Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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24
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Circulating microRNA miR-137 as a stable biomarker for methamphetamine abstinence. Psychopharmacology (Berl) 2022; 239:831-840. [PMID: 35138425 PMCID: PMC8891205 DOI: 10.1007/s00213-022-06074-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 01/24/2022] [Indexed: 12/01/2022]
Abstract
OBJECTIVE Stimulant use instigates abstinence syndrome in humans. miRNAs are a critical component for the pathophysiology of stimulant abstinence. Here we sought to identify a miRNA marker of methamphetamine abstinence in the circulating extracellular vesicles (cEVs). METHODS miR-137 in the cEVs was quantified by qPCR in thirty-seven patients under methamphetamine abstinence and thirty-five age-matched healthy controls recruited from 2014 to 2016 from the general adult population in a hospital setting, Seoul, South Korea. Diagnostic power was evaluated by area under curve in the receiver-operating characteristics curve and other multiple statistical parameters. RESULTS Patients under methamphetamine abstinence exhibited a significant reduction in cEV miR-137. Overall, cEV miR-137 had high potential as a blood-based marker of methamphetamine abstinence. cEV miR-137 retained the diagnostic power irrespective of the duration of methamphetamine abstinence or methamphetamine use. Interestingly, cEV miR-137 interacted with age: Control participants displayed an aging-dependent reduction of cEV miR-137, while methamphetamine-abstinent patients showed an aging-dependent increase in cEV miR-137. Accordingly, cEV miR-137 had variable diagnostic power depending on age, in which cEV miR-137 more effectively discriminated methamphetamine abstinence in the younger population. Duration of methamphetamine use or abstinence, cigarette smoking status, depressive disorder, or antidepressant treatment did not interact with the methamphetamine abstinence-induced reduction of cEV miR-137. CONCLUSION Our data collectively demonstrated that miR-137 in the circulating extracellular vesicles held high potential as a stable and accurate diagnostic marker of methamphetamine abstinence syndrome.
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25
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Smartphone-Based Device for Colorimetric Detection of MicroRNA Biomarkers Using Nanoparticle-Based Assay. SENSORS 2021; 21:s21238044. [PMID: 34884049 PMCID: PMC8659705 DOI: 10.3390/s21238044] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/27/2021] [Indexed: 01/15/2023]
Abstract
The detection of microRNAs (miRNAs) is emerging as a clinically important tool for the non-invasive detection of a wide variety of diseases ranging from cancers and cardiovascular illnesses to infectious diseases. Over the years, miRNA detection schemes have become accessible to clinicians, but they still require sophisticated and bulky laboratory equipment and trained personnel to operate. The exceptional computing ability and ease of use of modern smartphones coupled with fieldable optical detection technologies can provide a useful and portable alternative to these laboratory systems. Herein, we present the development of a smartphone-based device called Krometriks, which is capable of simple and rapid colorimetric detection of microRNA (miRNAs) using a nanoparticle-based assay. The device consists of a smartphone, a 3D printed accessory, and a custom-built dedicated mobile app. We illustrate the utility of Krometriks for the detection of an important miRNA disease biomarker, miR-21, using a nanoplasmonics-based assay developed by our group. We show that Krometriks can detect miRNA down to nanomolar concentrations with detection results comparable to a laboratory-based benchtop spectrophotometer. With slight changes to the accessory design, Krometriks can be made compatible with different types of smartphone models and specifications. Thus, the Krometriks device offers a practical colorimetric platform that has the potential to provide accessible and affordable miRNA diagnostics for point-of-care and field applications in low-resource settings.
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26
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Max KEA, Wang VR, Chang MS, Liau J, Weiss ZR, Morgan S, Li J, Bogardus KA, Morozov P, Suryawanshi H, Akat KM, Ben-Dov IZ, Hurley AM, Dowd K, Williams Z, Tuschl T. Plasma microRNA Interindividual Variability in Healthy Individuals, Pregnant Women, and an Individual with a Stably Altered Neuroendocrine Phenotype. Clin Chem 2021; 67:1676-1688. [PMID: 34850840 DOI: 10.1093/clinchem/hvab193] [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: 06/18/2021] [Accepted: 09/01/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Extracellular RNAs (exRNAs) in biofluids are amenable to quantitative analysis and proposed as noninvasive biomarkers for monitoring organ function. Cell-lineage-specific microRNAs (miRNAs) are present in plasma as soluble ribonucleoproteins or enclosed in exRNA carriers and transported through the vasculature. However, more extensive studies of healthy individuals are needed to gain insights into the variability of plasma miRNA abundance and composition. METHODS The exRNA composition of platelet-depleted plasma collected twice from 236 healthy individuals was characterized by small RNA sequencing. Plasma of pregnant women featuring dramatically increased placental miRNAs and samples from subject P12 with noticeably increased epithelial- and neuroendocrine-origin miRNAs were included for comparison. The miRNA content of 10 000g and 100 000g pellet fractions of plasma generated by ultracentrifugation was also determined. Data analysis methods included Pearson correlation, differential gene expression, and unsupervised clustering. RESULTS The abundance changes for more variable miRNAs in plasma of normal individuals correlated between coexpressed cell-lineage-specific miRNAs of the liver, neuroendocrine organs, epithelial cells, and muscle. ExRNA of pellet fractions contained <2% of total plasma miRNA with modest enrichment of lineage-specific and variable miRNAs compared to supernatant. The abundance fold changes of miRNAs observed in pregnancy and P12 compared to normal exceeded interquartile variability of healthy individuals. The neuroendocrine miRNA signature of P12 persisted for more than 4 years and was absent in other individuals. CONCLUSIONS This study defines the framework and effect size for screening of extensive plasma collections for miRNA phenotypes and biomarker discovery.
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Affiliation(s)
- Klaas E A Max
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
| | - Victoria R Wang
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
| | - Michael S Chang
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
| | - Jonathan Liau
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
| | - Zachary R Weiss
- Department of Obstetrics and Gynecology, Columbia University Medical Center, Columbia University Irving Medical Center, New York, NY
| | - Stephanie Morgan
- Department of Obstetrics and Gynecology, Columbia University Medical Center, Columbia University Irving Medical Center, New York, NY
| | - Jenny Li
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
| | | | - Pavel Morozov
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
| | - Hemant Suryawanshi
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY.,Department of Obstetrics and Gynecology, Columbia University Medical Center, Columbia University Irving Medical Center, New York, NY
| | - Kemal M Akat
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY.,Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Iddo Z Ben-Dov
- Department of Nephrology, Hadassah-Hebrew University Medical Center, Jerusalem, IL
| | - Arlene M Hurley
- Clinical Research Facilitation Office, Rockefeller University, New York, NY
| | - Kathleen Dowd
- Clinical Research Facilitation Office, Rockefeller University, New York, NY
| | - Zev Williams
- Department of Obstetrics and Gynecology, Columbia University Medical Center, Columbia University Irving Medical Center, New York, NY
| | - Thomas Tuschl
- Rockefeller University, Laboratory for RNA Molecular Biology, New York, NY
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27
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Rani R, Kela A, Dhaniya G, Arya K, Tripathi AK, Ahirwar R. Circulating microRNAs as biomarkers of environmental exposure to polycyclic aromatic hydrocarbons: potential and prospects. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:54282-54298. [PMID: 34402004 DOI: 10.1007/s11356-021-15810-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 07/31/2021] [Indexed: 06/13/2023]
Abstract
Exposure to polycyclic aromatic hydrocarbons (PAHs) produced from various pyrogenic and petrogenic sources in the environment has been linked to a variety of toxic effects in the human body. Genome-wide analyses have shown that microRNAs (miRNAs) can function as novel and minimally invasive biomarkers of environmental exposure to PAHs. The objective of this study is to explore miRNA signatures associated with early health effects in response to chronic environmental exposure to PAHs. We systematically searched Scopus and PubMed databases for studies related to exposure of PAHs with changes in miRNA expression patterns that represent early health effects in the exposed population. Based on previous studies, we included 15 cell-based and 9 each of animal model and human population-based studies for assessment. A total of 11 differentially expressed PAH-responsive miRNAs were observed each in two or more cell-based studies (miR-181a and miR-30c-1), animal model studies (miR-291a and miR-292), and human population-based studies (miR-126, miR-142-5p, miR-150-5p, miR-24-3p, miR-27a-3p, miR-28-5p, and miR-320b). In addition, miRNAs belonging to family miR-122, miR-199, miR-203, miR-21, miR-26, miR-29, and miR-92 were found to be PAH-responsive in both animal model and cell-based studies; let-7, miR-126, miR-146, miR-30, and miR-320 in both cell-based and human population-based studies; and miR-142, miR-150, and miR-27 were found differentially expressed in both animal model and human population-based studies. The only miRNA whose expression was found to be altered in all the three groups of studies is miR-34c. Association of environmental exposure to PAHs with altered expression of specific miRNAs indicates that selective miRNAs can be used as early warning biomarkers in PAH-exposed population.
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Affiliation(s)
- Rupa Rani
- Department of Environmental Biochemistry, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India
| | - Abhidha Kela
- Department of Environmental Biochemistry, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India
| | - Geeta Dhaniya
- Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, 226031, India
| | - Kamini Arya
- Department of Environmental Biochemistry, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India
| | - Amit K Tripathi
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India
- Department of Biotechnology, New Delhi, 110003, India
| | - Rajesh Ahirwar
- Department of Environmental Biochemistry, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India.
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28
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Albadawy R, Agwa SHA, Khairy E, Saad M, El Touchy N, Othman M, Matboli M. Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study. Biomedicines 2021; 9:1248. [PMID: 34572434 PMCID: PMC8472260 DOI: 10.3390/biomedicines9091248] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/15/2021] [Accepted: 09/15/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. METHODS Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients' sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. RESULTS We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. CONCLUSION This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.
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Affiliation(s)
- Reda Albadawy
- Department of Gastroentrology, Hepatology & Infectious Disease, Faculty of Medicine, Benha University, Benha 13518, Egypt;
| | - Sara H. A. Agwa
- Molecular Genomics Unit, Clinical Pathology Department, Medical Ain Shams Research Institute (MASRI), School of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Eman Khairy
- Medicinal Biochemistry and Molecular Biology Department, School of Medicine, Ain Shams University, Cairo 11566, Egypt;
| | - Maha Saad
- Biochemistry Department, Faculty of Medicine, Modern University for Technology and Information, Cairo 11382, Egypt;
| | - Naglaa El Touchy
- Department of Gastroentrology, Hepatology & Infectious Disease, Faculty of Medicine, Benha University, Benha 13518, Egypt;
| | - Mohamed Othman
- Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX 77030, USA;
| | - Marwa Matboli
- Medicinal Biochemistry and Molecular Biology Department, School of Medicine, Ain Shams University, Cairo 11566, Egypt;
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29
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Jamshidi S, Bokharaei-Salim F, Nahand JS, Monavari SH, Moghoofei M, Garshasbi S, Kalantari S, Esghaei M, Mirzaei H. Evaluation of the expression pattern of 4 microRNAs and their correlation with cellular/viral factors in PBMCs of Long Term non-progressors and HIV infected naïve Individuals. Curr HIV Res 2021; 20:42-53. [PMID: 34493187 DOI: 10.2174/1570162x19666210906143136] [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: 03/11/2021] [Revised: 07/08/2021] [Accepted: 07/21/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear. OBJECTIVE The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs. METHODS MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed. RESULTS The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression. CONCLUSION The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring.
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Affiliation(s)
- Sogol Jamshidi
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran. Iran
| | - Farah Bokharaei-Salim
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran. Iran
| | - Javid Sadri Nahand
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran. Iran
| | - Seyed Hamidreza Monavari
- Departments of Infectious Diseases and Tropical Medicine, Iran University of Medical Sciences, Tehran. Iran
| | - Mohsen Moghoofei
- Department of Microbiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah. Iran
| | | | - Saeed Kalantari
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran. Iran
| | - Maryam Esghaei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran. Iran
| | - Hamed Mirzaei
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran. Iran
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30
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Mc Cormack BA, González-Cantó E, Agababyan C, Espinoza-Sánchez NA, Tomás-Pérez S, Llueca A, Marí-Alexandre J, Götte M, Gilabert-Estellés J. miRNAs in the Era of Personalized Medicine: From Biomarkers to Therapeutics. Int J Mol Sci 2021; 22:8154. [PMID: 34360918 PMCID: PMC8348078 DOI: 10.3390/ijms22158154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 07/07/2021] [Indexed: 11/17/2022] Open
Abstract
In recent years, interest in personalized medicine has considerably increased [...].
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Affiliation(s)
- Bárbara A. Mc Cormack
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; (B.A.M.C.); (E.G.-C.); (C.A.); (S.T.-P.); (J.G.-E.)
| | - Eva González-Cantó
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; (B.A.M.C.); (E.G.-C.); (C.A.); (S.T.-P.); (J.G.-E.)
| | - Cristina Agababyan
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; (B.A.M.C.); (E.G.-C.); (C.A.); (S.T.-P.); (J.G.-E.)
- Obstetrics and Gynaecology Service, General University Hospital of Valencia Consortium, 46014 Valencia, Spain
| | - Nancy A. Espinoza-Sánchez
- Research Laboratory, Department of Gynecology and Obstetrics, Münster University Hospital, D-48149 Münster, Germany;
| | - Sarai Tomás-Pérez
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; (B.A.M.C.); (E.G.-C.); (C.A.); (S.T.-P.); (J.G.-E.)
| | - Antoni Llueca
- Department of Medicine, University Jaume I, 12071 Castellón, Spain;
- Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery (MUAPOS), General University Hospital of Castellón, 12004 Castellón, Spain
| | - Josep Marí-Alexandre
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; (B.A.M.C.); (E.G.-C.); (C.A.); (S.T.-P.); (J.G.-E.)
| | - Martin Götte
- Research Laboratory, Department of Gynecology and Obstetrics, Münster University Hospital, D-48149 Münster, Germany;
| | - Juan Gilabert-Estellés
- Research Laboratory in Biomarkers in Reproduction, Gynaecology and Obstetrics, Research Foundation of the General University Hospital of Valencia, 46014 Valencia, Spain; (B.A.M.C.); (E.G.-C.); (C.A.); (S.T.-P.); (J.G.-E.)
- Obstetrics and Gynaecology Service, General University Hospital of Valencia Consortium, 46014 Valencia, Spain
- Department of Paediatrics, Obstetrics and Gynaecology, University of Valencia, 46010 Valencia, Spain
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Ramzan F, Vickers MH, Mithen RF. Epigenetics, microRNA and Metabolic Syndrome: A Comprehensive Review. Int J Mol Sci 2021; 22:ijms22095047. [PMID: 34068765 PMCID: PMC8126218 DOI: 10.3390/ijms22095047] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
Epigenetics refers to the DNA chemistry changes that result in the modification of gene transcription and translation independently of the underlying DNA coding sequence. Epigenetic modifications are reported to involve various molecular mechanisms, including classical epigenetic changes affecting DNA methylation and histone modifications and small RNA-mediated processes, particularly that of microRNAs. Epigenetic changes are reversible and are closely interconnected. They are recognised to play a critical role as mediators of gene regulation, and any alteration in these mechanisms has been identified to mediate various pathophysiological conditions. Moreover, genetic predisposition and environmental factors, including dietary alterations, lifestyle or metabolic status, are identified to interact with the human epigenome, highlighting the importance of epigenetic factors as underlying processes in the aetiology of various diseases such as MetS. This review will reflect on how both the classical and microRNA-regulated epigenetic changes are associated with the pathophysiology of metabolic syndrome. We will then focus on the various aspects of epigenetic-based strategies used to modify MetS outcomes, including epigenetic diet, epigenetic drugs, epigenome editing tools and miRNA-based therapies.
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Galluzzo A, Gallo S, Pardini B, Birolo G, Fariselli P, Boretto P, Vitacolonna A, Peraldo-Neia C, Spilinga M, Volpe A, Celentani D, Pidello S, Bonzano A, Matullo G, Giustetto C, Bergerone S, Crepaldi T. Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing. ESC Heart Fail 2021; 8:2907-2919. [PMID: 33934544 PMCID: PMC8318428 DOI: 10.1002/ehf2.13371] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/22/2021] [Accepted: 04/06/2021] [Indexed: 12/20/2022] Open
Abstract
Aims Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. Methods and results We performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty‐two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR‐210‐3p, miR‐22‐5p, miR‐22‐3p, miR‐21‐3p, miR‐339‐3p, and miR‐125a‐5p) significantly correlated with HF biomarkers, among which N‐terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR‐125a‐5p, miR‐10b‐5p, and miR‐9‐5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio‐HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82). Conclusions This discovery study has characterized, for the first time, the advanced chronic HF‐specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations.
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Affiliation(s)
- Alessandro Galluzzo
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.,Ospedale Sant'Andrea, Vercelli, Italy
| | - Simona Gallo
- Department of Oncology, University of Turin, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy
| | - Barbara Pardini
- Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.,Italian Institute for Genomic Medicine (IIGM), Turin, Italy
| | - Giovanni Birolo
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Piero Fariselli
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Paolo Boretto
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Annapia Vitacolonna
- Department of Oncology, University of Turin, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy
| | - Caterina Peraldo-Neia
- Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy.,Laboratory of Cancer Genomics, Fondazione Edo ed Elvo Tempia, Biella, Italy
| | | | - Alessandra Volpe
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Dario Celentani
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Stefano Pidello
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | | | - Giuseppe Matullo
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Carla Giustetto
- Department of Medical Sciences, University of Turin, Turin, Italy.,A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Serena Bergerone
- A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy
| | - Tiziana Crepaldi
- Department of Oncology, University of Turin, Turin, Italy.,Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy
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Lassandro G, Ciaccia L, Amoruso A, Palladino V, Palmieri VV, Giordano P. Focus on MicroRNAs as Biomarker in Pediatric Diseases. Curr Pharm Des 2021; 27:826-832. [PMID: 33087027 DOI: 10.2174/1381612826666201021125512] [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: 05/01/2020] [Accepted: 09/25/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND MiRNAs are a class of small non-coding RNAs that are involved in the post-transcriptional regulation of gene expression. MiRNAs are considered a class of epigenetic biomarkers. These biomarkers can investigate disease at different stages: diagnosis, therapy or clinical follow-up. OBJECTIVE The aim of this paper is to highlight the innovative use of miRNAs in several childhood diseases. METHODS We conducted a literature review to search the usage of miRNAs in pediatric clinical routine or experimental trials. RESULTS We found a possible key role of miRNAs in different pediatric illnesses (metabolic alterations, coagulation defects, cancer). CONCLUSION The modest literature production denotes that further investigation is needed to assess and validate the promising role of miRNAs as non-invasive biomarkers in pediatric disorders.
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Affiliation(s)
- Giuseppe Lassandro
- Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Loredana Ciaccia
- Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Anna Amoruso
- Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Valentina Palladino
- Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Viviana V Palmieri
- Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
| | - Paola Giordano
- Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy
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Expression profiling of miRNA-196a biomarker in naïve hepatitis C virus-infected and Sofosbuvir plus Daclatasvir-treated patients. Arch Microbiol 2021; 203:2365-2371. [PMID: 33660021 DOI: 10.1007/s00203-021-02233-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 12/31/2020] [Accepted: 02/11/2021] [Indexed: 10/22/2022]
Abstract
Micro-RNA (miRNA) is a short stretch of nucleotides that can regulate many genes associated with the various stages of the hepatitis C virus (HCV) life cycle and disease progression. This study evaluates the expression profiling of miRNA-196a in naïve HCV-infected, and Sofosbuvir plus Daclatasvir-treated patients. MiRNA-196a can inhibit HCV replication by silencing the HCV NS5A protein or downregulating the human BACH-I mRNA. The expression level of miRNA-196a was determined by quantitative reverse transcription PCR (RT-qPCR) using the whole RNA extracted from the recruited participant's serum. Results showed a 0.83-fold decrease in the miRNA-196a level in naïve HCV-infected than controls. On the contrary, an increase in the expression level by 0.06-fold was observed in Sofosbuvir plus Daclatasvir-treated patients. A negative but significant correlation was recorded between the HCV-RNA load and miRNA-196a expression level in the naïve-infected patients. Serum miRNA-196a ROC curve analysis revealed an area under the curve of 0.8278 (95% CI 0.7033-0.9524, p < 0.0001) with 82.05% sensitivity and 76.19% specificity in discriminating the healthy controls from the HCV-infected samples. In conclusion, our study explored the comparative expression levels of miRNA-196a in HCV-infected and Sofosbuvir plus Daclatasvir patients. Further studies are needed to examine the possible role of miR-196a as a therapeutic agent for treating HCV-infected patients.
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Aggio-Bruce R, Chu-Tan JA, Wooff Y, Cioanca AV, Schumann U, Natoli R. Inhibition of microRNA-155 Protects Retinal Function Through Attenuation of Inflammation in Retinal Degeneration. Mol Neurobiol 2021; 58:835-854. [PMID: 33037565 PMCID: PMC7843561 DOI: 10.1007/s12035-020-02158-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 10/01/2020] [Indexed: 01/14/2023]
Abstract
Although extensively investigated in inflammatory conditions, the role of pro-inflammatory microRNAs (miRNAs), miR-155 and miR-146a, has not been well-studied in retinal degenerative diseases. We therefore aimed to explore the role and regulation of these miRNA in the degenerating retina, with a focus on miR-155. C57BL/6J mice were subjected to photo-oxidative damage for up to 5 days to induce focal retinal degeneration. MiR-155 expression was quantified by qRT-PCR in whole retina, serum, and small-medium extracellular vesicles (s-mEVs), and a PrimeFlow™ assay was used to identify localisation of miR-155 in retinal cells. Constitutive miR-155 knockout (KO) mice and miR-155 and miR-146a inhibitors were utilised to determine the role of these miRNA in the degenerating retina. Electroretinography was employed as a measure of retinal function, while histological quantification of TUNEL+ and IBA1+ positive cells was used to quantify photoreceptor cell death and infiltrating immune cells, respectively. Upregulation of miR-155 was detected in retinal tissue, serum and s-mEVs in response to photo-oxidative damage, localising to the nucleus of a subset of retinal ganglion cells and glial cells and in the cytoplasm of photoreceptors. Inhibition of miR-155 showed increased function from negative controls and a less pathological pattern of IBA1+ cell localisation and morphology at 5 days photo-oxidative damage. While neither dim-reared nor damaged miR-155 KO animals showed retinal histological difference from controls, following photo-oxidative damage, miR-155 KO mice showed increased a-wave relative to controls. We therefore consider miR-155 to be associated with the inflammatory response of the retina in response to photoreceptor-specific degeneration.
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Affiliation(s)
- Riemke Aggio-Bruce
- The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, Australian Capital Territory, 2601, Australia
- The Australian National University Medical School, Mills Road, Australian Capital Territory, Acton, 2601, Australia
| | - Joshua A Chu-Tan
- The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, Australian Capital Territory, 2601, Australia
- The Australian National University Medical School, Mills Road, Australian Capital Territory, Acton, 2601, Australia
| | - Yvette Wooff
- The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, Australian Capital Territory, 2601, Australia
- The Australian National University Medical School, Mills Road, Australian Capital Territory, Acton, 2601, Australia
| | - Adrian V Cioanca
- The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, Australian Capital Territory, 2601, Australia
| | - Ulrike Schumann
- The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, Australian Capital Territory, 2601, Australia
| | - Riccardo Natoli
- The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, Australian Capital Territory, 2601, Australia.
- The Australian National University Medical School, Mills Road, Australian Capital Territory, Acton, 2601, Australia.
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Unger L, Abril C, Gerber V, Jagannathan V, Koch C, Hamza E. Diagnostic potential of three serum microRNAs as biomarkers for equine sarcoid disease in horses and donkeys. J Vet Intern Med 2021; 35:610-619. [PMID: 33415768 PMCID: PMC7848377 DOI: 10.1111/jvim.16027] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 12/18/2020] [Accepted: 12/18/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) are potential biomarkers for equine sarcoids (ES). OBJECTIVES To assess eca-miR-331, eca-miR-100, and eca-miR-1 as serum biomarkers for ES disease. ANIMALS Sixty-eight ES cases (56 horses, 12 donkeys), 69 tumor-free controls (60 horses, 9 donkeys), and 20 horses with other skin tumors. METHODS For this case-control study, expression of serum eca-miR-331, eca-miR-100, and eca-miR-1 in ES-affected equids was compared to tumor-free age-, sex-, and breed-matched control horses and donkeys with other skin tumors using reverse transcription quantitative PCR (polymerase chain reaction) for relative miRNA quantification. Biological, preanalytical, and clinical variable influences on miRNA expression were examined. Receiver operator characteristic (ROC) curve analyses were used to determine differences in miRNA expression between groups. RESULTS The expression of eca-miR-100 was affected by age (P = .003) and expression of eca-miR-100 and eca-miR-1 were affected by hemolysis (both P < .001). Eca-miR-331 was unaffected by biological variation, hemolysis, ES type, and disease severity. Eca-miR-331 concentrations were higher in ES-affected compared to tumor-free controls (P = .002). The ROC curve analysis indicated an area under the curve of 0.65 (P = .002) with a sensitivity of 60%, specificity of 71%, and positive and negative likelihood ratios of 2.1 and 0.56, respectively, to diagnose ES. Eca-miR-331 expression did not discriminate between horses with ES and other skin tumors. Expression of eca-miR-100 and eca-miR-1 was not different between groups. CONCLUSIONS AND CLINICAL IMPORTANCE Serum eca-miR-331 expression is neither sensitive nor specific enough as a single ES biomarker. If combined with other miRNAs, it may be helpful for ES diagnosis.
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Affiliation(s)
- Lucia Unger
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine (ISME), Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland
| | - Carlos Abril
- Institute of Virology and Immunology, University of Bern, Bern, Switzerland
| | - Vinzenz Gerber
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine (ISME), Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland
| | - Vidhya Jagannathan
- Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Christoph Koch
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine (ISME), Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland
| | - Eman Hamza
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine (ISME), Vetsuisse Faculty, University of Bern, and Agroscope, Bern, Switzerland
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Hosseinipour M, Shahbazi S, Roudbar-Mohammadi S, Khorasani M, Marjani M. Differential genes expression analysis of invasive aspergillosis: a bioinformatics study based on mRNA/microRNA. MOLECULAR BIOLOGY RESEARCH COMMUNICATIONS 2020; 9:173-180. [PMID: 33344664 PMCID: PMC7731968 DOI: 10.22099/mbrc.2020.37432.1509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Invasive aspergillosis is a severe opportunistic infection with high mortality in immunocompromised patients. Recently, the roles of microRNAs have been taken into consideration in the immune system and inflammatory responses. Using bioinformatics approaches, we aimed to study the microRNAs related to invasive aspergillosis to understand the molecular pathways involved in the disease pathogenesis. Data were extracted from the gene expression omnibus (GEO) database. We proposed 3 differentially expressed genes; S100B, TDRD9 and TMTC1 related to pathogenesis of invasive aspergillosis. Using miRWalk 2.0 predictive tool, microRNAs that targeted the selected genes were identified. The roles of microRNAs were investigated by microRNA target prediction and molecular pathways analysis. The significance of combined expression changes in selected genes was analyzed by ROC curves study. Thirty-three microRNAs were identified as the common regulator of S100B, TDRD9 and TMTC1 genes. Several of them were previously reported in the pathogenesis of fungal infections including miR-132. Predicted microRNAs were involved in innate immune response as well as toll-like receptor signaling. Most of the microRNAs were also linked to platelet activation. The ROC chart in the combination mode of S100B/TMTC1, showed the sensitivity of 95.65 percent and the specificity of 69.23 percent. New approaches are needed for rapid and accurate detection of invasive aspergillosis. Given the pivotal signaling pathways involved, predicted microRNAs can be considered as the potential candidates of the disease diagnosis. Further investigation of the microRNAs expression changes and related pathways would lead to identifying the effective biomarkers for IA detection.
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Affiliation(s)
- Maryam Hosseinipour
- Department of Medical Mycology, Faculty of Medical Science, Tarbiat Modares University, Tehran Iran
| | - Shirin Shahbazi
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Shahla Roudbar-Mohammadi
- Department of Medical Mycology, Faculty of Medical Science, Tarbiat Modares University, Tehran Iran
| | - Maryam Khorasani
- Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran
| | - Majid Marjani
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas. Cell Rep 2020; 33:108552. [PMID: 33378673 DOI: 10.1016/j.celrep.2020.108552] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 10/14/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023] Open
Abstract
Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease. Where most studies focus on blood-derived fluids, other biofluids may be more informative. We present an atlas of messenger, circular, and small RNA transcriptomes of a comprehensive collection of 20 human biofluids. By means of synthetic spike-in controls, we compare RNA content across biofluids, revealing a 10,000-fold difference in concentration. The circular RNA fraction is increased in most biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. Our atlas enables an informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Spike-normalized data are publicly available in the R2 web portal for further exploration.
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Florio MC, Magenta A, Beji S, Lakatta EG, Capogrossi MC. Aging, MicroRNAs, and Heart Failure. Curr Probl Cardiol 2020; 45:100406. [PMID: 30704792 PMCID: PMC10544917 DOI: 10.1016/j.cpcardiol.2018.12.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Accepted: 12/23/2018] [Indexed: 12/12/2022]
Abstract
Aging is a major risk factor for heart failure, one of the leading causes of death in Western society. The mechanisms that underlie the different forms of heart failure have been elucidated only in part and the role of noncoding RNAs is still poorly characterized. Specifically, microRNAs (miRNAs), a class of small noncoding RNAs that can modulate gene expression at the posttranscriptional level in all cells, including myocardial and vascular cells, have been shown to play a role in heart failure with reduced ejection fraction. In contrast, miRNAs role in heart failure with preserved ejection fraction, the predominant form of heart failure in the elderly, is still unknown. In this review, we will focus on age-dependent miRNAs in heart failure and on some other conditions that are prevalent in the elderly and are frequently associated with heart failure with preserved ejection fraction.
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40
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Hulstaert E, Morlion A, Levanon K, Vandesompele J, Mestdagh P. Candidate RNA biomarkers in biofluids for early diagnosis of ovarian cancer: A systematic review. Gynecol Oncol 2020; 160:633-642. [PMID: 33257015 DOI: 10.1016/j.ygyno.2020.11.018] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 11/14/2020] [Indexed: 12/27/2022]
Abstract
Ovarian cancer is often diagnosed in an advanced stage and is associated with a high mortality rate. It is assumed that early detection of ovarian cancer could improve patient outcomes. Unfortunately, effective screening methods for early diagnosis of ovarian cancer are still lacking. Extracellular RNAs circulating in human biofluids can reliably be measured and are emerging as potential biomarkers in cancer. In this systematic review, we present 75 RNA biomarkers detectable in human biofluids that have been studied for early diagnosis of ovarian cancer. The majority of these markers are microRNAs identified using RT-qPCR or microarrays in blood-based fluids. A handful of studies used RNA-sequencing and explored alternative fluids, such as urine and ascites. Candidate RNA biomarkers that were more abundant in biofluids of ovarian cancer patients compared to controls in at least two independent studies include miR-21, the miR-200 family, miR-205, miR-10a and miR-346. Amongst the markers confirmed to be lower in at least two studies are miR-122, miR-193a, miR-223, miR-126 and miR-106b. While these biomarkers show promising diagnostic potential, further validation is required before implementation in routine clinical care. Challenges related to biomarker validation and reflections on future perspectives to accelerate progress in this field are discussed.
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Affiliation(s)
- Eva Hulstaert
- Department of Biomolecular Medicine, Ghent University, Corneel Heymanslaan 10, Ghent 9000, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Corneel Heymanslaan 10, Ghent 9000, Belgium; Department of Dermatology, Ghent University Hospital, Corneel Heymanslaan 10, Ghent 9000, Belgium.
| | - Annelien Morlion
- Department of Biomolecular Medicine, Ghent University, Corneel Heymanslaan 10, Ghent 9000, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Corneel Heymanslaan 10, Ghent 9000, Belgium.
| | - Keren Levanon
- Sheba Cancer Research Center, Chaim Sheba Medical Center, Ramat Gan 52621, Israel; Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
| | - Jo Vandesompele
- Department of Biomolecular Medicine, Ghent University, Corneel Heymanslaan 10, Ghent 9000, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Corneel Heymanslaan 10, Ghent 9000, Belgium.
| | - Pieter Mestdagh
- Department of Biomolecular Medicine, Ghent University, Corneel Heymanslaan 10, Ghent 9000, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Corneel Heymanslaan 10, Ghent 9000, Belgium.
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Kuchay MS, Choudhary NS, Mishra SK. Pathophysiological mechanisms underlying MAFLD. Diabetes Metab Syndr 2020; 14:1875-1887. [PMID: 32998095 DOI: 10.1016/j.dsx.2020.09.026] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 09/21/2020] [Accepted: 09/23/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The pathophysiology underlying metabolic associated fatty liver disease (MAFLD) involves a multitude of interlinked processes, including insulin resistance (IR) underlying the metabolic syndrome, lipotoxicity attributable to the accumulation of toxic lipid species, infiltration of proinflammatory cells causing hepatic injury and ultimately leading to hepatic stellate cell (HSC) activation and fibrogenesis. The proximal processes, such as IR, lipid overload and lipotoxicity are relatively well established, but the downstream molecular mechanisms, such as inflammatory processes, hepatocyte lipoapoptosis, and fibrogenesis are incompletely understood. METHODS A literature search was performed with Medline (PubMed), Scopus and Google Scholar electronic databases till June 2020, using relevant keywords (nonalcoholic fatty liver disease; metabolic associated fatty liver disease; nonalcoholic steatohepatitis; NASH pathogenesis) to extract relevant studies describing pathogenesis of MAFLD/MASH. RESULTS Several studies have reported new concepts underlying pathophysiology of MAFLD. Activation of HSCs is the common final pathway for diverse signals from damaged hepatocytes and proinflammatory cells. Activated HSCs then secrete excess extracellular matrix (ECM) which accumulates and impairs structure and function of the liver. TAZ (a transcriptional regulator), hedgehog (HH) ligands, transforming growth factor-β (TGF-β), bone morphogenetic protein 8B (BMP8B) and osteopontin play important roles in activating these HSCs. Dysfunctional gut microbiome, dysregulated bile acid metabolism, endogenous alcohol production, and intestinal fructose handling, modify individual susceptibility to MASH. CONCLUSIONS Newer concepts of pathophysiology underlying MASH, such as TAZ/Ihh pathway, extracellular vesicles, microRNA, dysfunctional gut microbiome and intestinal fructose handling present promising targets for the development of therapeutic agents.
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Affiliation(s)
- Mohammad Shafi Kuchay
- Division of Endocrinology and Metabolism, Medanta the Medicity Hospital, Gurugram, 122001, Haryana, India.
| | - Narendra Singh Choudhary
- Institute of Digestive and Hepatobiliary Sciences, Medanta-The Medicity Hospital, Gurugram, 122001, Haryana, India
| | - Sunil Kumar Mishra
- Division of Endocrinology and Metabolism, Medanta the Medicity Hospital, Gurugram, 122001, Haryana, India
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Mandala A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients 2020; 12:E3166. [PMID: 33081177 PMCID: PMC7602751 DOI: 10.3390/nu12103166] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/12/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions.
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Affiliation(s)
- Ashok Mandala
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
| | - Rachel C. Janssen
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
| | - Sirish Palle
- Department of Pediatrics, Section of Gastroenterology, Hepatology & Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Kevin R. Short
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
- Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Jacob E. Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (A.M.); (R.C.J.); (K.R.S.)
- Department of Pediatrics, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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Unique Interplay Between Molecular miR-181b/d Biomarkers and Health Related Quality of Life Score in the Predictive Glioma Models. Int J Mol Sci 2020; 21:ijms21207450. [PMID: 33050332 PMCID: PMC7589546 DOI: 10.3390/ijms21207450] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 09/30/2020] [Accepted: 10/07/2020] [Indexed: 11/18/2022] Open
Abstract
In the last decade, an increasing amount of research has been conducted analyzing microRNA expression changes in glioma tissue and its expressed exosomes, but there is still sparse information on microRNAs or other biomarkers and their association with patients’ functional/psychological outcomes. In this study, we performed a combinational analysis measuring miR-181b and miR-181d expression levels by quantitative polymerase chain reaction (qPCR), evaluating isocitrate dehydrogenase 1 (IDH1) single nucleotide polymorphism (SNP), and O-6-methylguanine methyltransferase (MGMT) promoter methylation status in 92 post-surgical glioma samples and 64 serum exosomes, including patients’ quality of life evaluation applying European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-30), EORTC the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), and the Karnofsky performance status (KPS). The tumoral expression of miR-181b was lower in grade III and glioblastoma, compared to grade II glioma patients (p < 0.05). Additionally, for the first time, we demonstrated the association between miR-181 expression levels and patients’ quality of life. A positive correlation was observed between tumoral miR-181d levels and glioma patients’ functional parameters (p < 0.05), whereas increased exosomal miR-181b levels indicated a worse functional outcome (p < 0.05). Moreover, elevated miR-181b exosomal expression can indicate a significantly shorter post-surgical survival time for glioblastoma multiforme (GBM) patients. In addition, both tumoral and exosomal miR-181 expression levels were related to patients’ functioning and tumor-related symptoms. Our study adds to previous findings by demonstrating the unique interplay between molecular miR-181b/d biomarkers and health related quality of life (HRQOL) score as both variables remained significant in the predictive glioma models.
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Li JR, Tong CY, Sung TJ, Kang TY, Zhou XJ, Liu CC. CMEP: a database for circulating microRNA expression profiling. Bioinformatics 2020; 35:3127-3132. [PMID: 30668638 DOI: 10.1093/bioinformatics/btz042] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 12/29/2018] [Accepted: 01/18/2019] [Indexed: 01/18/2023] Open
Abstract
MOTIVATION In recent years, several experimental studies have revealed that the microRNAs (miRNAs) in serum, plasma, exosome and whole blood are dysregulated in various types of diseases, indicating that the circulating miRNAs may serve as potential noninvasive biomarkers for disease diagnosis and prognosis. However, no database has been constructed to integrate the large-scale circulating miRNA profiles, explore the functional pathways involved and predict the potential biomarkers using feature selection between the disease conditions. Although there have been several studies attempting to generate a circulating miRNA database, they have not yet integrated the large-scale circulating miRNA profiles or provided the biomarker-selection function using machine learning methods. RESULTS To fill this gap, we constructed the Circulating MicroRNA Expression Profiling (CMEP) database for integrating, analyzing and visualizing the large-scale expression profiles of phenotype-specific circulating miRNAs. The CMEP database contains massive datasets that were manually curated from NCBI GEO and the exRNA Atlas, including 66 datasets, 228 subsets and 10 419 samples. The CMEP provides the differential expression circulating miRNAs analysis and the KEGG functional pathway enrichment analysis. Furthermore, to provide the function of noninvasive biomarker discovery, we implemented several feature-selection methods, including ridge regression, lasso regression, support vector machine and random forests. Finally, we implemented a user-friendly web interface to improve the user experience and to visualize the data and results of CMEP. AVAILABILITY AND IMPLEMENTATION CMEP is accessible at http://syslab5.nchu.edu.tw/CMEP.
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Affiliation(s)
- Jian-Rong Li
- Institute of Genomics and Bioinformatics.,Advanced Plant Biotechnology Center, National Chung Hsing University, Taichung City 402, Taiwan
| | | | | | | | - Xianghong Jasmine Zhou
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Chun-Chi Liu
- Institute of Genomics and Bioinformatics.,Advanced Plant Biotechnology Center, National Chung Hsing University, Taichung City 402, Taiwan
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Zong Y, Yan J, Jin L, Xu B, He Z, Zhang R, Hu C, Jia W. Relationship between circulating miR-132 and non-alcoholic fatty liver disease in a Chinese population. Hereditas 2020; 157:22. [PMID: 32443971 PMCID: PMC7245036 DOI: 10.1186/s41065-020-00136-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 05/11/2020] [Indexed: 02/07/2023] Open
Abstract
Background Non-invasive diagnostic markers are of great importance for early screening nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) play significant roles in many metabolic disease, including NAFLD. Therefore, this study focusd on a Chinese population to explore the possible correlation between circulating miR-132 and NAFLD. Results Serum miR-132 was positively associated with NAFLD in non-type 2 diabetes mellitus (T2DM) groups by logistic regression (OR = 3.082 [1.057, 8.988], P = 0.039) after adjusting age, sex, and body mass index (BMI). Additionally, in non-T2DM subgroup, after adjusting age, sex, bmi, serum miR-132 was significantly associated with ALT (β ± SE = 0.005 ± 0.002, P = 0.018), TG (β ± SE = 0.072 ± 0.029, P = 0.015), FPG (β ± SE = 0.123 ± 0.058, P = 0.036), γ-GT (β ± SE = 0.002 ± 0.001, P = 0.047), apoE (β ± SE = 0.038 ± 0.002, P = 0.017) . Conclusions Serum miR-132 was found to be associated with NAFLD risk in a Chinese cross-section study. This finding provides a prospective research direction for early screening and diagnosing NAFLD.
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Affiliation(s)
- Yicen Zong
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Jing Yan
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Li Jin
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Bo Xu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Zhen He
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Rong Zhang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China
| | - Cheng Hu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
| | - Weiping Jia
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
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Koi Y, Tsutani Y, Nishiyama Y, Ueda D, Ibuki Y, Sasada S, Akita T, Masumoto N, Kadoya T, Yamamoto Y, Takahashi RU, Tanaka J, Okada M, Tahara H. Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles. Cancer Sci 2020; 111:2104-2115. [PMID: 32215990 PMCID: PMC7293081 DOI: 10.1111/cas.14393] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 03/15/2020] [Accepted: 03/17/2020] [Indexed: 12/26/2022] Open
Abstract
Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA‐based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer‐free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR‐21‐5p (3′ addition C), miR‐23a‐3p and tRF‐Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early‐stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF‐7 and MDA‐MB‐231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.
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Affiliation(s)
- Yumiko Koi
- Surgical Oncology, Division of Radiation Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yasuhiro Tsutani
- Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yukie Nishiyama
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daisuke Ueda
- Surgical Oncology, Division of Radiation Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yuta Ibuki
- Surgical Oncology, Division of Radiation Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Shinsuke Sasada
- Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Norio Masumoto
- Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Takayuki Kadoya
- Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Yuki Yamamoto
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ryou-U Takahashi
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Research Center for Radiation Casualty Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
| | - Hidetoshi Tahara
- Department of Cellular and Molecular Biology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Collaborative laboratory of Liquid Biopsy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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47
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Garcia CM, Toms SA. The Role of Circulating MicroRNA in Glioblastoma Liquid Biopsy. World Neurosurg 2020; 138:425-435. [PMID: 32251831 DOI: 10.1016/j.wneu.2020.03.128] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 03/20/2020] [Accepted: 03/22/2020] [Indexed: 12/29/2022]
Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive primary malignancy of the central nervous system. The standard used to monitor disease progression and therapeutic response has been magnetic resonance imaging, which is usually obtained preoperatively and postoperatively. Patients with GBM are monitored every 2-3 months and scans are repeated until progression is detected. Sometimes there is an inability to detect tumor progression or difficulty in differentiating tumor progression from pseudoprogression. With the difficulty of distinguishing disease progression, as well as the cost of imaging, there may be a need for the existence of a noninvasive liquid biopsy. There is no reliable biomarker for GBM that can be used for liquid biopsy, but if one could be detected in serum or cerebrospinal fluid and vary with tumor burden, then, it could be developed into one. MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that posttranscriptionally control gene expression. They play vital roles in tumor progression, migration, invasion, and stemness. Because miRNAs are secreted in stable forms in bodily fluid, either via extracellular vesicles or in cell-free form, they have great potential as biomarkers that can be used for liquid biopsy. Various miRNAs that are dysregulated in GBM have been identified in tissue, cerebrospinal fluid, and serum samples. There needs to be standardization of sample collection and quantification for both cell-free and exosomal-derived samples. Further studies need to be performed on larger cohorts to evaluate the sensitivity and specificity of not just miRNAs but most potential biomarkers.
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Affiliation(s)
- Catherine M Garcia
- Department of Neurosurgery, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
| | - Steven A Toms
- Department of Neurosurgery, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
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Hamamoto O, Tirapelli DPDC, Lizarte Neto FS, Freitas-Lima P, Saggioro FP, Cirino MLDA, Assirati JA, Serafini LN, Velasco TR, Sakamoto AC, Carlotti CG. Modulation of NMDA receptor by miR-219 in the amygdala and hippocampus of patients with mesial temporal lobe epilepsy. J Clin Neurosci 2020; 74:180-186. [PMID: 32111564 DOI: 10.1016/j.jocn.2020.02.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 02/10/2020] [Indexed: 01/28/2023]
Abstract
Mesial temporal lobe epilepsy with hippocampal sclerosis is the most frequent form of focal epilepsy in adults, and it is often refractory to drug treatment. Regardless of the efforts on developing new antiepileptic drugs for refractory cases, studies suggest a need for better understanding the molecular bases of epilepsy. The microRNAs have been progressively investigated as potential targets for both epilepsy mechanisms elucidation and treatment. Therefore, the goal of this study was to evaluate the differential expression of miR-219, miR-181b, and miR-195, previously described as regulators of the excitatory neurotransmitter receptors NMDA-R1 and AMPA-GluR2 and inhibitory neurotransmitter GABAA (α2, β3, and γ2 subunits) in the amygdala and hippocampus of patients with mesial temporal lobe epilepsy. Based on genes and miRNAs' quantitative Polymerase Chain Reaction (qPCR) from 18 patients with epilepsy, our results showed an inverse relationship between miR-219 and NMDA-NR1 expression in both the amygdala and hippocampus in comparison to their expression in controls. NR1 and GluR2 were upregulated in the amygdala of epileptic patients. Low miR-195 expression was observed in the amygdala of patients with epilepsy. Our findings indicate that miR-219 has a possible regulatory role in excitatory neurotransmission in patients with epilepsy, contributing to the new avenue of miRNA biology in drug-resistant epilepsy, reserving huge potential for future applications and clinical interventions in conjunction with existing therapies.
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Affiliation(s)
- Osmi Hamamoto
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | | | - Fermino Sanches Lizarte Neto
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Priscila Freitas-Lima
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil; Barao de Maua University Center, Ribeirao Preto, SP, Brazil
| | - Fabiano Pinto Saggioro
- Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Mucio Luiz de Assis Cirino
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - João Alberto Assirati
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Luciano Neder Serafini
- Department of Pathology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Tonicarlo Rodrigues Velasco
- Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Américo Ceiki Sakamoto
- Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
| | - Carlos Gilberto Carlotti
- Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
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Liu X, Cui X, Guan G, Dong Y, Zhang Z. microRNA-192-5p is involved in nerve repair in rats with peripheral nerve injury by regulating XIAP. Cell Cycle 2020; 19:326-338. [PMID: 31944167 PMCID: PMC7028159 DOI: 10.1080/15384101.2019.1710916] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/20/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
Objective: MicroRNAs (miRNAs) have been demonstrated to engage in the nerve injury, while the effect of microRNA-192-5p (miR-192-5p) on the nerve repair has not yet been well understood. This study is performed to investigate how miR-192-5p affects nerve repair in rats with peripheral nerve injury by regulating X-linked inhibitor of apoptosis protein (XIAP).Methods: The rat model of left sciatic nerve injury was established, and the expression of miR-192-5p was then detected. A series of experiments were conducted to investigate the role of miR-192-5p on nerve repair in rats with peripheral nerve injury. The expression of apoptosis-related proteins (Caspase-3, Bax and Bcl-2) and nerve repair factors (NGF, BDNF, and GAP-43) was measured. Bioinformatics analysis and dual-luciferase reporter gene assay confirmed the targeting relationship between miR-192-5p and XIAP.Results: MiR-192-5p inhibition promoted the recovery of sensory function and the recovery and regeneration in rats with sciatic nerve injury. MiR-192-5p inhibition promoted the recovery of muscle atrophy caused by nerve injury. MiR-192-5p inhibition inhibited neuronal apoptosis by affecting the expression of apoptosis-related proteins and promoted the recovery of nerve function by elevating the expression of nerve repair factors induced by peripheral nerve injury. Bioinformatics analysis and dual-luciferase reporter gene assay confirmed that XIAP was a target gene of miR-192-5p.Conclusion: This study demonstrates that miR-192-5p inhibition can up-regulate the expression of XIAP, decrease the apoptosis of nerve cells, and promote the repair and regeneration of peripheral nerve injury.
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Affiliation(s)
- Xing Liu
- Department of orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Xintao Cui
- Department of orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Guangwei Guan
- Department of orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ying Dong
- Department of orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Zhenyu Zhang
- Department of orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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50
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Gao Y, Liu M, Shi S, Sun Y, Li M, Zhang M, Sheng Z, Zhang J, Tian J. Diagnostic value of seven biomarkers for breast cancer: an overview with evidence mapping and indirect comparisons of diagnostic test accuracy. Clin Exp Med 2020; 20:97-108. [PMID: 31894424 DOI: 10.1007/s10238-019-00598-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 12/03/2019] [Indexed: 02/06/2023]
Abstract
Several meta-analyses have evaluated the value of biomarkers in diagnosing breast cancer, but which biomarker has the optimal diagnostic value remains unclear. This overview aimed to compare the accuracy of different biomarkers in diagnosing breast cancer. PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched. The assessment of multiple systematic reviews-2 (AMSTAR-2) was used to assess the methodological quality and preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy (PRISMA-DTA) for reporting quality. Pairwise meta-analyses were performed to estimate the pooled results for each biomarker, and indirect comparisons were conducted to compare diagnostic accuracy between biomarkers. Eleven systematic reviews (SRs) involving 218 original studies were included. All SRs were of critically low methodological quality, 3 SRs had minimal reporting flaws and 8 SRs had minor flaws. The pooled sensitivity and specificity were 0.77 and 0.87 for miRNA, 0.70 and 0.87 for circulating cell-free DNA, 0.29 and 0.96 for APC gene promoter methylation, 0.69 and 0.99 for 14-3-3σ promoter methylation, 0.63 and 0.82 for CA153, 0.58 and 0.87 for CEA, and 0.73 and 0.56 for PSA. Compared with CA153 and PSA, miRNA had a higher sensitivity and specificity. The sensitivity of miRNA was higher than circulating cell-free DNA and CEA, although they had the same specificities. APC gene promoter methylation and 14-3-3σ promoter methylation were more specific than miRNA, but they had unacceptably low sensitivity. In conclusion, miRNA had better diagnostic accuracy than the other six biomarkers. But due to the low quality of included SRs, the results need to be interpreted with caution. Further study should investigate the diagnostic accuracy of different biomarkers in direct comparisons and focus on the value of combined biomarkers.
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Affiliation(s)
- Ya Gao
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, No. 199, Donggang West Road, Lanzhou City, 730000, Gansu Province, China
| | - Ming Liu
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, No. 199, Donggang West Road, Lanzhou City, 730000, Gansu Province, China
| | - Shuzhen Shi
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, No. 199, Donggang West Road, Lanzhou City, 730000, Gansu Province, China
| | - Yue Sun
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, No. 199, Donggang West Road, Lanzhou City, 730000, Gansu Province, China
| | - Muyang Li
- The Second Clinical Medical College of Lanzhou University, Lanzhou, China
| | - Mei Zhang
- Department of Radiology, Gansu Provincial Cancer Hospital, Lanzhou, China
| | - Zhijuan Sheng
- Department of Galactophore, Gansu Provincial Cancer Hospital, Lanzhou, China
| | - Junhua Zhang
- Evidence-Based Medicine Center, Tianjin University of Traditional Chinese Medicine, No. 312 Anshanxi Street, Nankai District, Tianjin, 300193, China.
| | - Jinhui Tian
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
- Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, No. 199, Donggang West Road, Lanzhou City, 730000, Gansu Province, China.
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