|
1
|
Ramirez-Gomez J, Dalal S, Devara D, Sharma B, Rodarte D, Kumar S. MicroRNA-based recent research developments in Alzheimer's disease. J Alzheimers Dis 2025; 104:14-31. [PMID: 39894921 DOI: 10.1177/13872877241313397] [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] [Indexed: 02/04/2025]
Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by memory and physical impairment in aged individuals. microRNAs (miRNAs) are small, single-stranded noncoding RNAs that induce translational repression by binding to the 3' UTR of a target mRNA. miRNAs play a crucial role in neurological activity by mediating cellular proliferation, synaptic plasticity, apoptosis and more. Ongoing research in patents and clinical trials have called attention to promising miRNAs as biomarkers and therapeutics in AD. Recent research has shown that miRNAs are aberrantly expressed in AD brain, blood, cerebrospinal fluid and serum. Attenuated miRNA expressions have diagnostic potential in AD by interacting with amyloid-β synthesis, phosphorylated tau, and neurofibrillary tangles. In this study, miRNA-29a, miRNA-125b, miRNA-34a, miRNA-146a, and miRNA-155 have shown promise as potential biomarker candidates for AD. Improving cognitive symptoms can be traced to restoring the endogenous miRNA activity by synthesizing miRNA mimics and miRNA antisense oligonucleotides. miRNA-483-5p, miRNA-188-5p, miRNA-219, miRNA135a/5p, miRNA-23/23b-3p, miRNA-124, and miRNA-455-3p are growing therapeutics for AD. However, miRNA-based therapeutics struggle outside of preclinical testing. miRNA-107, miRNA-206, miRNA-30/7, and miRNA-142-3p face bottlenecks in clinical trials due to a lack of experimental design, transparency and volunteer size. Patenting recent miRNA-based developments demonstrates the commitment in identifying a new biomarker and/or therapeutic for AD.
Collapse
Affiliation(s)
- Jaime Ramirez-Gomez
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Sarthak Dalal
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Davin Devara
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Bhupender Sharma
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Daniela Rodarte
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Subodh Kumar
- Center of Emphasis in Neuroscience, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA
- L. Frederick Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, USA
| |
Collapse
|
|
2
|
Kushwaha S, Goel A, Singh AV. Serum microRNA Biomarker Expression in HIV and TB: A Concise Overview. Infect Disord Drug Targets 2025; 25:e18715265305638. [PMID: 39506419 DOI: 10.2174/0118715265305638240930054842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 08/22/2024] [Accepted: 08/23/2024] [Indexed: 11/08/2024]
Abstract
Non-coding RNAs (ncRNAs), specifically MicroRNAs or miRNAs, are now understood to be essential regulators in the complex field of gene expression. By selectively binding to certain mRNA targets, these tiny RNA molecules control the expression of genes, leading to mRNA degradation or translational repression. The discovery of miRNAs has significantly advanced biomedical research, particularly in elucidating the molecular mechanisms underlying various diseases and exploring innovative therapeutic approaches. Recent progress in miRNA research has provided insights into their biogenesis, functional roles, and potential clinical applications. Despite the absence of established methodologies for clinical implementation, miRNAs show great promise as diagnostic and therapeutic agents for a wide array of diseases. Their distinctive attributes, such as high specificity, sensitivity, and accessibility, position them as ideal candidates for biomarker development and targeted therapy. Achieving a comprehensive understanding of miRNA biology and functionality is crucial to fully harnessing their potential in medicine. Ongoing research efforts aim to unravel the intricate mechanisms of miRNA-mediated gene regulation and to develop novel approaches for utilizing miRNAs in disease diagnosis, prognosis, and treatment. This review provides a comprehensive analysis of current knowledge on miRNAs, focusing on their biogenesis, regulatory mechanisms, and potential clinical applications. By synthesizing existing evidence and highlighting key research findings, this review aims to inspire further exploration into the diverse roles of miRNAs in health and disease. Ultimately, this endeavour could result in the development of innovative miRNA-based diagnostic and therapeutic strategies.
Collapse
Affiliation(s)
- Shweta Kushwaha
- Department of Microbiology and Molecular Biology, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, Uttar Pradesh, India
- Department of Biotechnology, GLA University, Mathura, 281406, Uttar Pradesh, India
| | - Anjana Goel
- Department of Biotechnology, GLA University, Mathura, 281406, Uttar Pradesh, India
| | - Ajay Vir Singh
- Department of Microbiology and Molecular Biology, ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, 282004, Uttar Pradesh, India
| |
Collapse
|
|
3
|
Mack T, Gianferri T, Niedermayer A, Debatin KM, Meyer LH, Muench V. Benchmarking miRNA reference genes in B-cell precursor acute lymphoblastic leukemia. Sci Rep 2024; 14:26390. [PMID: 39488607 PMCID: PMC11531470 DOI: 10.1038/s41598-024-77733-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024] Open
Abstract
MicroRNAs (miRNAs) play dual roles in acute lymphoblastic leukemia (ALL) as both tumor suppressors and oncogenes, and miRNA expression profiles can be used for patient risk stratification. Precise assessment of miRNA levels is crucial for understanding their role and function in gene regulation. Quantitative real-time polymerase chain reaction (qPCR) is a reliable, rapid, and cost-effective method for analyzing miRNA expression, assuming that appropriate normalization to stable references is performed to ensure valid data. In this study, we evaluated the stability of six commonly used miRNA references (5sRNA, SNORD44, RNU6, RNU1A1, miR-103a-3p, and miR-532-5p) across nine B-cell precursor (BCP) ALL cell lines, 22 patient-derived xenograft (PDX) BCP ALL samples from different organ compartments of leukemia bearing mice, and peripheral blood mononuclear cells (PBMCs) from six healthy donors. We used four different algorithms (Normfinder, ∆CT, geNorm, and BestKeeper) to assess the most stably expressed reference across all samples. Moreover, we validated our data in an additional set of 13 PDX ALL samples and six healthy controls, identifying miR-103a-3p and miR-532-5p as the most stable references for miRNA normalization in BCP ALL studies. Additionally, we demonstrated the critical importance of using a stable reference to accurately interpret miRNA data.
Collapse
Affiliation(s)
- Teresa Mack
- Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
| | - Tommaso Gianferri
- Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
| | - Alexandra Niedermayer
- Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
- International Graduate School in Molecular Medicine, Ulm University, Ulm, Germany
| | - Klaus-Michael Debatin
- Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
| | - Lüder H Meyer
- Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
| | - Vera Muench
- Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
| |
Collapse
|
|
4
|
Adamova P, Powell AK, Dykes IM. Assessment of NanoString technology as a tool for profiling circulating miRNA in maternal blood during pregnancy. EXTRACELLULAR VESICLES AND CIRCULATING NUCLEIC ACIDS 2024; 5:471-496. [PMID: 39697629 PMCID: PMC11648433 DOI: 10.20517/evcna.2024.38] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 08/09/2024] [Accepted: 08/24/2024] [Indexed: 12/20/2024]
Abstract
Aim Circulating maternal MicroRNA (miRNA) is a promising source of biomarkers for antenatal diagnostics. NanoString nCounter is a popular global screening tool due to its simplicity and ease of use, but there is a lack of standardisation in analysis methods. We examined the effect of user-defined variables upon reported changes in maternal blood miRNA during pregnancy. Methods Total RNA was prepared from the maternal blood of pregnant and control rats. miRNA expression was profiled using Nanostring nCounter. Raw count data were processed using nSolver using different combinations of normalisation and background correction methods as well as various background thresholds. A panel of 14 candidates in which changes were supported by multiple analysis workflows was selected for validation by RT-qPCR. We then reverse-engineered the nSolver analysis to gain further insight. Results Thirty-one putative differentially expressed miRNAs were identified by nSolver. However, each analysis workflow produced a different set of reported biomarkers and none of them was common to all analysis methods. Four miRNAs with known roles in pregnancy (miR-183, miR-196c, miR-431, miR-450a) were validated. No single nSolver analysis workflow could successfully identify all four validated changes. Reverse engineering revealed errors in nSolver data processing which compound the inherent problems associated with background correction and normalisation. Conclusion Our results suggest that user-defined variables greatly influence the output of the assay. This highlights the need for standardised nSolver data analysis methods and detailed reporting of these methods. We suggest that investigators in the future should not rely on a single analysis method to identify changes and should always validate screening results.
Collapse
Affiliation(s)
- Petra Adamova
- Department of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
- Liverpool Centre for Cardiovascular Science, Institute for Health Research, Liverpool John Moores University, Liverpool L3 3AF, UK
| | - Andrew K. Powell
- Department of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
- Liverpool Centre for Cardiovascular Science, Institute for Health Research, Liverpool John Moores University, Liverpool L3 3AF, UK
| | - Iain M. Dykes
- Department of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
- Liverpool Centre for Cardiovascular Science, Institute for Health Research, Liverpool John Moores University, Liverpool L3 3AF, UK
| |
Collapse
|
|
5
|
Yu L, Peng Y, Sheng M, Wang Q, Jin Z, Huang J, Yang X. Electrochemical Biosensing Platform Based on Toehold-Mediated Strand Displacement Reaction and DSN Enzyme-Assisted Amplification for Two-Target Detection. ACS APPLIED MATERIALS & INTERFACES 2024; 16:45695-45703. [PMID: 39157906 DOI: 10.1021/acsami.4c08515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/20/2024]
Abstract
Simultaneous detection of multiple targets is of great significance for accurate disease diagnosis. Herein, based on duplex-specific nuclease (DSN) assisted signal amplification and the toehold-mediated strand displacement reaction (TSDR), we constructed an electrochemical biosensor with high sensitivity and high specificity for dual-target detection. MiRNA-141 and miRNA-133a were used as the targets, and ferrocene (Fc) and methylene blue (MB) with significant peak potential differentiation were used as the electrochemical signal probes. The elaborately designed hairpin probe H1, which was fixed on the electrode surface, could be hybridized with the target miRNA-141 to perform signal amplification by the DSN-assisted enzyme cleavage cycle; thus, miRNA-141 could be detected by Fc signal changes at 0.41 V. The hairpin H1 can also combine with the MB-labeled signal probe (SP) output from miRNA-133a-induced TSDR, and the detection of miRNA-133a can be realized according to the response signal generated by MB at -0.26 V. The two sensing lines are independent of each other, and there is no mutual interference in the detection process. Therefore, two independent detection lines could be connected in series, and the simultaneous detection of two targets can be achieved on a single electrode. This novel detection strategy provides a new way to simultaneously detect different biomarkers.
Collapse
Affiliation(s)
- Linying Yu
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Yao Peng
- Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Mengting Sheng
- Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Qian Wang
- Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Zhiying Jin
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Jianshe Huang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
| | - Xiurong Yang
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| |
Collapse
|
|
6
|
Yan Y, Liao L. MicroRNA Expression Profile in Patients Admitted to ICU as Novel and Reliable Approach for Diagnostic and Therapeutic Purposes. Mol Biotechnol 2024; 66:1357-1375. [PMID: 37314613 DOI: 10.1007/s12033-023-00767-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Accepted: 05/06/2023] [Indexed: 06/15/2023]
Abstract
The ability to detect early metabolic changes in patients who have an increased mortality risk in the intensive care units (ICUs) could increase the likelihood of predicting recovery patterns and assist in disease management. Markers that can predict the disease progression of patients in the ICU might also be beneficial for improving their medical profile. Although biomarkers have been used in the ICU more frequently in recent years, the clinical use of most of them is limited. A wide range of biological processes are influenced by microRNAs (miRNAs) that modulate the translation and stability of specific mRNAs. Studies suggest that miRNAs may serve as a diagnostic and therapeutic biomarker in ICUs by profiling miRNA dysregulation in patient samples. To improve the predictive value of biomarkers for ICU patients, researchers have proposed both investigating miRNAs as novel biomarkers and combining them with other clinical biomarkers. Herein, we discuss recent approaches to the diagnosis and prognosis of patients admitted to an ICU, highlighting the use of miRNAs as novel and robust biomarkers for this purpose. In addition, we discuss emerging approaches to biomarker development and ways to improve the quality of biomarkers so that patients in ICU get the best outcomes possible.
Collapse
Affiliation(s)
- Youqin Yan
- ICU Department, People's Hospital of Changshan, Changshan, China
| | - Linjun Liao
- ICU Department, People's Hospital of Changshan, Changshan, China.
| |
Collapse
|
|
7
|
Endale HT, Mariye YF, Negash HK, Hassen FS, Asrat WB, Mengstie TA, Tesfaye W. MiRNA in cervical cancer: Diagnosis to therapy: Systematic review. Heliyon 2024; 10:e24398. [PMID: 38317930 PMCID: PMC10839805 DOI: 10.1016/j.heliyon.2024.e24398] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 12/22/2023] [Accepted: 01/08/2024] [Indexed: 02/07/2024] Open
Abstract
Cancers are one of the most public health problems worldwide. Among them, cervical cancer (CC) is the fourth most prevalent cancer with 604 000 new cases and 342 000 deaths. Mostly, it is associated with Human papillomavirus (HPV). It has been caused by the aggregation of genetic and epigenetic modifications in cervical epithelial cells. Although genetic mutations are given great attention for the carcinogenesis of CC, epigenetic changes have emerged as a hotspot area for CC biomarkers research with great implications for early diagnosis, prognosis, and treatment response prediction of the disease. Recently, there are several studies focused on miRNAs as biomarkers of cervical cancer. However, the precise function of miRNAs in the development of cervical cancer is not still completely understood, particularly when it comes to unconventional sampling materials like cervical mucus and plasma serum. Hence, this review article will give a summary of the miRNAs profiles that emerge at different stages of cervical cancer progression and their downstream effects on target genes and associated signaling pathways. Finally, these results may provide insight into the use of miRNAs as biomarkers for the prediction or diagnosis of cervical cancer or the development of miRNA-based therapeutics against cervical cancer.
Collapse
Affiliation(s)
- Hiwot Tezera Endale
- Department of Biochemistry, School of Medicine, College of Medicine & Health Sciences, University of Gondar, Ethiopia
| | - Yitbarek Fantahun Mariye
- Department of Obstetrics & Gynecology, School of Medicine, College of Medicine & Health Sciences, Addis Ababa University, Ethiopia
| | - Habtu Kifle Negash
- Department of Human Anatomy, School of Medicine, College of Medicine & Health Sciences, University of Gondar, Ethiopia
| | - Fethiya Seid Hassen
- Department of Biochemistry, School of Medicine, College of Medicine & Health Sciences, University of Gondar, Ethiopia
| | - Wastina Bitewlign Asrat
- Department of Biochemistry, School of Medicine, College of Medicine & Health Sciences, University of Gondar, Ethiopia
| | - Tiget Ayelgn Mengstie
- Department of Biochemistry, School of Medicine, College of Medicine & Health Sciences, University of Gondar, Ethiopia
| | - Winta Tesfaye
- Department of Human Physiology, School of Medicine, College of Medicine & Health Sciences, University of Gondar, Ethiopia
| |
Collapse
|
|
8
|
Novacescu D, Latcu SC, Bardan R, Daminescu L, Cumpanas AA. Contemporary Biomarkers for Renal Transplantation: A Narrative Overview. J Pers Med 2023; 13:1216. [PMID: 37623466 PMCID: PMC10456039 DOI: 10.3390/jpm13081216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/18/2023] [Accepted: 07/28/2023] [Indexed: 08/26/2023] Open
Abstract
Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies.
Collapse
Affiliation(s)
- Dorin Novacescu
- Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania;
| | - Silviu Constantin Latcu
- Doctoral School, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania;
- Department of Urology, “Pius Brinzeu” Timisoara County Emergency Hospital, Liviu Rebreanu Boulevard, Nr. 156, 300723 Timisoara, Romania; (R.B.); (L.D.); (A.A.C.)
- Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
| | - Razvan Bardan
- Department of Urology, “Pius Brinzeu” Timisoara County Emergency Hospital, Liviu Rebreanu Boulevard, Nr. 156, 300723 Timisoara, Romania; (R.B.); (L.D.); (A.A.C.)
- Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
| | - Liviu Daminescu
- Department of Urology, “Pius Brinzeu” Timisoara County Emergency Hospital, Liviu Rebreanu Boulevard, Nr. 156, 300723 Timisoara, Romania; (R.B.); (L.D.); (A.A.C.)
| | - Alin Adrian Cumpanas
- Department of Urology, “Pius Brinzeu” Timisoara County Emergency Hospital, Liviu Rebreanu Boulevard, Nr. 156, 300723 Timisoara, Romania; (R.B.); (L.D.); (A.A.C.)
- Department XV, Discipline of Urology, Victor Babes University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square, No. 2, 300041 Timisoara, Romania
| |
Collapse
|
|
9
|
Padroni L, De Marco L, Dansero L, Fiano V, Milani L, Vasapolli P, Manfredi L, Caini S, Agnoli C, Ricceri F, Sacerdote C. An Epidemiological Systematic Review with Meta-Analysis on Biomarker Role of Circulating MicroRNAs in Breast Cancer Incidence. Int J Mol Sci 2023; 24:3910. [PMID: 36835336 PMCID: PMC9967215 DOI: 10.3390/ijms24043910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/06/2023] [Accepted: 02/09/2023] [Indexed: 02/17/2023] Open
Abstract
Breast cancer (BC) is a multifactorial disease caused by an interaction between genetic predisposition and environmental exposures. MicroRNAs are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and seem to be related to cancer risk factors. We conducted a systematic review and meta-analysis to identify circulating microRNAs related to BC diagnosis, paying special attention to methodological problems in this research field. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seventy-five studies were included in the systematic review. A meta-analysis was performed for microRNAs analyzed in at least three independent studies where sufficient data to make analysis were presented. Seven studies were included in the MIR21 and MIR155 meta-analysis, while four studies were included in the MIR10b metanalysis. The pooled sensitivity and specificity of MIR21 for BC diagnosis were 0.86 (95%CI 0.76-0.93) and 0.84 (95%CI 0.71-0.92), 0.83 (95%CI 0.72-0.91) and 0.90 (95%CI 0.69-0.97) for MIR155, and 0.56 (95%CI 0.32-0.71) and 0.95 (95%CI 0.88-0.98) for MIR10b, respectively. Several other microRNAs were found to be dysregulated, distinguishing BC patients from healthy controls. However, there was little consistency between included studies, making it difficult to identify specific microRNAs useful for diagnosis.
Collapse
Affiliation(s)
- Lisa Padroni
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| | - Laura De Marco
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| | - Lucia Dansero
- Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Valentina Fiano
- Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Lorenzo Milani
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| | - Paolo Vasapolli
- Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | - Luca Manfredi
- Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
| | - Saverio Caini
- Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139 Florence, Italy
| | - Claudia Agnoli
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
| | - Fulvio Ricceri
- Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
- Unit of Epidemiology, Regional Health Service ASL TO3, 10095 Grugliasco, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Via Santena 7, 10126 Turin, Italy
| |
Collapse
|
|
10
|
Cowan E, Karagiannopoulos A, Eliasson L. MicroRNAs in Type 2 Diabetes: Focus on MicroRNA Profiling in Islets of Langerhans. Methods Mol Biol 2022; 2592:113-142. [PMID: 36507989 DOI: 10.1007/978-1-0716-2807-2_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Differential expression of microRNAs (miRNAs) is observed in many diseases including type 2 diabetes (T2D). Insulin secretion from pancreatic beta cells is central for the regulation of blood glucose levels and failure to release enough insulin results in hyperglycemia and T2D. The importance in T2D pathogenesis of single miRNAs in beta cells has been described; however, to get the full picture, high-throughput miRNA sequencing is necessary. Here we describe a method using small RNA sequencing, from sample preparation to expression analysis using bioinformatic tools. In the end, a tutorial on differential expression analysis is presented in R using publicly available data.
Collapse
Affiliation(s)
- Elaine Cowan
- Unit of Islet Cell Exocytosis, Department of Clinical Sciences - Malmö, Lund University Diabetes Centre (LUDC), Lund University, Clinical Research Centre, and Skåne University Hospital (SUS), Malmö, Sweden
| | - Alexandros Karagiannopoulos
- Unit of Islet Cell Exocytosis, Department of Clinical Sciences - Malmö, Lund University Diabetes Centre (LUDC), Lund University, Clinical Research Centre, and Skåne University Hospital (SUS), Malmö, Sweden
| | - Lena Eliasson
- Unit of Islet Cell Exocytosis, Department of Clinical Sciences - Malmö, Lund University Diabetes Centre (LUDC), Lund University, Clinical Research Centre, and Skåne University Hospital (SUS), Malmö, Sweden.
| |
Collapse
|
|
11
|
Loga L, Dican L, Matei HV, Mărunțelu I, Constantinescu I. Relevant biomarkers of kidney allograft rejection. J Med Life 2022; 15:1330-1333. [PMID: 36567832 PMCID: PMC9762359 DOI: 10.25122/jml-2022-0181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/19/2022] [Indexed: 12/27/2022] Open
Abstract
This review focuses on the new relevant biomarkers proposed for the diagnosis of different types of allograft rejections. The immune response against the transplanted tissues can lead to rejection. Kidney allograft rejection occurs when the recipient component's immune system reacts against the donor's cells. MicroRNAs, dd-cf DNA, CD103 markers, CXCR3 chemokine receptor, IP-10, KIR genes, HLA antibodies, the perforin and granzyme B molecules - the constant assessment of all these parameters could prevent acute rejection episodes and kidney injuries. In this way, both immune response and tissue destruction biomarkers are essential for the long-term survival of kidney-transplanted patients. They also contribute to personalizing treatments, precisely personalized immunosuppressive regiments.
Collapse
Affiliation(s)
- Luminița Loga
- Clinical Institute of Urology and Renal Transplant, Cluj-Napoca, Romania,Department of Cell and Molecular Biology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Lucia Dican
- Clinical Institute of Urology and Renal Transplant, Cluj-Napoca, Romania,Department of Biochemistry, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Horea Vladi Matei
- Department of Cell and Molecular Biology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ion Mărunțelu
- Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania,Centre of Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania,Corresponding Author: Ion Mărunțelu, Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. Centre of Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania. E-mail:
| | - Ileana Constantinescu
- Immunology and Transplant Immunology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania,Centre of Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania
| |
Collapse
|
|
12
|
Nagatake Y, Sato M, Mouri Y, Tomita N. Fully automated microRNA quantification technique based on bioluminescent enzyme immunoassay. Anal Biochem 2022; 656:114880. [PMID: 36063916 DOI: 10.1016/j.ab.2022.114880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 11/15/2022]
Abstract
MicroRNAs (miRNAs) are potential clinical biomarkers for the detection of various diseases. However, their quantification has not been implemented in clinical practice given the inconsistencies in their variable recovery rate and accuracy of the results. Thus, we utilized a technique based on bioluminescent enzyme immunoassay (BLEIA) to perform fully automated miRNA quantification using magnetic particles conjugated with antibodies targeting DNA-RNA hybrids, biotinylated DNA probes specific to miRNAs, and firefly luciferase-labeled streptavidin. This method enabled direct use of diluted serum and automation of all processes within 1 h. The results revealed a wide linear range between 10 fmol/L and 1 nmol/L, high sensitivity with a detection limit of 6.3 fmol/L or below, high specificity with a false positive rate under 2.4%, and high reproducibility in intra- and inter-experimental observations (under CV 10% and r = 0.9965, respectively). Furthermore, a significant correlation was revealed between quantitative reverse transcription-polymerase chain reaction and BLEIA assay for the quantification of synthetic miRNA (r = 0.9993) and endogenous miRNA in healthy serums (r = 0.8203), respectively. Overall, we developed a fully automated miRNA quantification method based on BLEIA, which can be adopted in a clinical setting. However, further studies are needed to assess its clinical performance.
Collapse
Affiliation(s)
- Yuka Nagatake
- Department-I, Biochemical Research Laboratory II, Eiken Chemical Co., Ltd., Shimoishigami, Tochigi, Japan
| | - Masaki Sato
- Department-I, Biochemical Research Laboratory II, Eiken Chemical Co., Ltd., Shimoishigami, Tochigi, Japan.
| | - Yuta Mouri
- Department-I, Biochemical Research Laboratory II, Eiken Chemical Co., Ltd., Shimoishigami, Tochigi, Japan
| | - Norihiro Tomita
- Department-I, Biochemical Research Laboratory II, Eiken Chemical Co., Ltd., Shimoishigami, Tochigi, Japan
| |
Collapse
|
|
13
|
Snyder M, Iraola-Guzmán S, Saus E, Gabaldón T. Discovery and Validation of Clinically Relevant Long Non-Coding RNAs in Colorectal Cancer. Cancers (Basel) 2022; 14:cancers14163866. [PMID: 36010859 PMCID: PMC9405614 DOI: 10.3390/cancers14163866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/04/2022] [Accepted: 08/04/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Recent efforts in biomedical research have focused on the identification of molecular biomarkers to improve the diagnosis, prognosis and eventually treatment of the most common human diseases worldwide, including cancer. In this context, a large number of studies point to a pivotal role of long non-coding RNAs (lncRNAs) in the pathophysiology of carcinogenesis, suggesting diagnostic or therapeutic potential. However, for most of them, supporting evidence is scarce and often based on a single large-scale analysis. Here, focusing on colorectal cancer (CRC), we present an overview of the main approaches for discovering and validating lncRNA candidate molecules, and provide a curated list of the most promising lncRNAs associated with this malignancy. Abstract Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with nearly two million newly diagnosed cases each year. The survival of patients with CRC greatly depends on the cancer stage at the time of diagnosis, with worse prognosis for more advanced cases. Consequently, considerable effort has been directed towards improving population screening programs for early diagnosis and identifying prognostic markers that can better inform treatment strategies. In recent years, long non-coding RNAs (lncRNAs) have been recognized as promising molecules, with diagnostic and prognostic potential in many cancers, including CRC. Although large-scale genome and transcriptome sequencing surveys have identified many lncRNAs that are altered in CRC, most of their roles in disease onset and progression remain poorly understood. Here, we critically review the variety of detection methods and types of supporting evidence for the involvement of lncRNAs in CRC. In addition, we provide a reference catalog that features the most clinically relevant lncRNAs in CRC. These lncRNAs were selected based on recent studies sorted by stringent criteria for both supporting experimental evidence and reproducibility.
Collapse
Affiliation(s)
- Madison Snyder
- Barcelona Supercomputing Centre (BSC-CNS), Plaça Eusebi Güell, 1-3, 08034 Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
| | - Susana Iraola-Guzmán
- Barcelona Supercomputing Centre (BSC-CNS), Plaça Eusebi Güell, 1-3, 08034 Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
| | - Ester Saus
- Barcelona Supercomputing Centre (BSC-CNS), Plaça Eusebi Güell, 1-3, 08034 Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
| | - Toni Gabaldón
- Barcelona Supercomputing Centre (BSC-CNS), Plaça Eusebi Güell, 1-3, 08034 Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
- Centro de Investigación Biomédica En Red de Enfermedades Infecciosas (CIBERINFEC), 08028 Barcelona, Spain
- Correspondence:
| |
Collapse
|
|
14
|
Takizawa S, Matsuzaki J, Ochiya T. Circulating microRNAs: Challenges with their use as liquid biopsy biomarkers. Cancer Biomark 2022; 35:1-9. [PMID: 35786647 DOI: 10.3233/cbm-210223] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Circulating microRNA (miRNA) is a major focus in liquid biopsy studies. The circulating levels of certain miRNAs have been suggested to reflect specific physiological conditions, and several studies have reported their potential use as biomarkers for the detection and prognosis of cancer, as well as for predicting responses to chemotherapy or radiotherapy. Alongside these biomarker studies, research into the effects of specific background factors on circulating miRNA levels is progressing. Indeed, several studies have shown that a number of factors, including blood sample collection and processing methods, as well as subject-specific factors such as age, sex, and other physiological conditions, can affect the normal levels of circulating miRNAs. Unfortunately, the evidence supporting these effects is not yet strong enough to support a definite conclusion and further research is warranted. Here, we summarize the findings of several studies that have addressed these concerns and identify important topics that should be considered when analyzing circulating miRNA levels in liquid biopsy studies.
Collapse
Affiliation(s)
- Satoko Takizawa
- New Projects Development Division, Toray Industries, Inc., Kanagawa, Japan
| | - Juntaro Matsuzaki
- Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan
| | - Takahiro Ochiya
- Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan
| |
Collapse
|
|
15
|
Beasley AB, Chen FK, Isaacs TW, Gray ES. Future perspectives of uveal melanoma blood based biomarkers. Br J Cancer 2022; 126:1511-1528. [PMID: 35190695 PMCID: PMC9130512 DOI: 10.1038/s41416-022-01723-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 01/15/2022] [Accepted: 01/27/2022] [Indexed: 01/06/2023] Open
Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy affecting adults. Despite successful local treatment of the primary tumour, metastatic disease develops in up to 50% of patients. Metastatic UM carries a particularly poor prognosis, with no effective therapeutic option available to date. Genetic studies of UM have demonstrated that cytogenetic features, including gene expression, somatic copy number alterations and specific gene mutations can allow more accurate assessment of metastatic risk. Pre-emptive therapies to avert metastasis are being tested in clinical trials in patients with high-risk UM. However, current prognostic methods require an intraocular tumour biopsy, which is a highly invasive procedure carrying a risk of vision-threatening complications and is limited by sampling variability. Recently, a new diagnostic concept known as "liquid biopsy" has emerged, heralding a substantial potential for minimally invasive genetic characterisation of tumours. Here, we examine the current evidence supporting the potential of blood circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), microRNA (miRNA) and exosomes as biomarkers for UM. In particular, we discuss the potential of these biomarkers to aid clinical decision making throughout the management of UM patients.
Collapse
Affiliation(s)
- Aaron B Beasley
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
- Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia
| | - Fred K Chen
- Centre for Ophthalmology and Visual Sciences (incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA, Australia
- Department of Ophthalmology, Royal Perth Hospital, Perth, WA, Australia
- Department of Ophthalmology, Perth Children's Hospital, Perth, WA, Australia
| | - Timothy W Isaacs
- Centre for Ophthalmology and Visual Sciences (incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA, Australia
- Department of Ophthalmology, Royal Perth Hospital, Perth, WA, Australia
- Perth Retina, West Leederville, WA, Australia
| | - Elin S Gray
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
- Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
- Centre for Ophthalmology and Visual Sciences (incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA, Australia.
| |
Collapse
|
|
16
|
Chatzopoulou F, Kyritsis KA, Papagiannopoulos CI, Galatou E, Mittas N, Theodoroula NF, Papazoglou AS, Karagiannidis E, Chatzidimitriou M, Papa A, Sianos G, Angelis L, Chatzidimitriou D, Vizirianakis IS. Dissecting miRNA–Gene Networks to Map Clinical Utility Roads of Pharmacogenomics-Guided Therapeutic Decisions in Cardiovascular Precision Medicine. Cells 2022; 11:cells11040607. [PMID: 35203258 PMCID: PMC8870388 DOI: 10.3390/cells11040607] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/29/2022] [Accepted: 01/31/2022] [Indexed: 02/04/2023] Open
Abstract
MicroRNAs (miRNAs) create systems networks and gene-expression circuits through molecular signaling and cell interactions that contribute to health imbalance and the emergence of cardiovascular disorders (CVDs). Because the clinical phenotypes of CVD patients present a diversity in their pathophysiology and heterogeneity at the molecular level, it is essential to establish genomic signatures to delineate multifactorial correlations, and to unveil the variability seen in therapeutic intervention outcomes. The clinically validated miRNA biomarkers, along with the relevant SNPs identified, have to be suitably implemented in the clinical setting in order to enhance patient stratification capacity, to contribute to a better understanding of the underlying pathophysiological mechanisms, to guide the selection of innovative therapeutic schemes, and to identify innovative drugs and delivery systems. In this article, the miRNA–gene networks and the genomic signatures resulting from the SNPs will be analyzed as a method of highlighting specific gene-signaling circuits as sources of molecular knowledge which is relevant to CVDs. In concordance with this concept, and as a case study, the design of the clinical trial GESS (NCT03150680) is referenced. The latter is presented in a manner to provide a direction for the improvement of the implementation of pharmacogenomics and precision cardiovascular medicine trials.
Collapse
Affiliation(s)
- Fani Chatzopoulou
- Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (F.C.); (A.P.); (D.C.)
- Labnet Laboratories, Department of Molecular Biology and Genetics, 54638 Thessaloniki, Greece
| | - Konstantinos A. Kyritsis
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (K.A.K.); (C.I.P.); (N.F.T.)
| | - Christos I. Papagiannopoulos
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (K.A.K.); (C.I.P.); (N.F.T.)
| | - Eleftheria Galatou
- Department of Life & Health Sciences, University of Nicosia, Nicosia 1700, Cyprus;
| | - Nikolaos Mittas
- Department of Chemistry, International Hellenic University, 65404 Kavala, Greece;
| | - Nikoleta F. Theodoroula
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (K.A.K.); (C.I.P.); (N.F.T.)
| | - Andreas S. Papazoglou
- 1st Cardiology Department, AHEPA University General Hospital of Thessaloniki, 54636 Thessaloniki, Greece; (A.S.P.); (E.K.); (G.S.)
| | - Efstratios Karagiannidis
- 1st Cardiology Department, AHEPA University General Hospital of Thessaloniki, 54636 Thessaloniki, Greece; (A.S.P.); (E.K.); (G.S.)
| | - Maria Chatzidimitriou
- Department of Biomedical Sciences, School of Health Sciences, International Hellenic University, 57400 Thessaloniki, Greece;
| | - Anna Papa
- Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (F.C.); (A.P.); (D.C.)
| | - Georgios Sianos
- 1st Cardiology Department, AHEPA University General Hospital of Thessaloniki, 54636 Thessaloniki, Greece; (A.S.P.); (E.K.); (G.S.)
| | - Lefteris Angelis
- Department of Informatics, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Dimitrios Chatzidimitriou
- Laboratory of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (F.C.); (A.P.); (D.C.)
| | - Ioannis S. Vizirianakis
- Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (K.A.K.); (C.I.P.); (N.F.T.)
- Department of Life & Health Sciences, University of Nicosia, Nicosia 1700, Cyprus;
- Correspondence: or
| |
Collapse
|
|
17
|
Gopcevic KR, Gkaliagkousi E, Nemcsik J, Acet Ö, Bernal-Lopez MR, Bruno RM, Climie RE, Fountoulakis N, Fraenkel E, Lazaridis A, Navickas P, Rochfort KD, Šatrauskienė A, Zupkauskienė J, Terentes-Printzios D. Pathophysiology of Circulating Biomarkers and Relationship With Vascular Aging: A Review of the Literature From VascAgeNet Group on Circulating Biomarkers, European Cooperation in Science and Technology Action 18216. Front Physiol 2021; 12:789690. [PMID: 34970157 PMCID: PMC8712891 DOI: 10.3389/fphys.2021.789690] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/17/2021] [Indexed: 12/14/2022] Open
Abstract
Impairment of the arteries is a product of sustained exposure to various deleterious factors and progresses with time; a phenomenon inherent to vascular aging. Oxidative stress, inflammation, the accumulation of harmful agents in high cardiovascular risk conditions, changes to the extracellular matrix, and/or alterations of the epigenetic modification of molecules, are all vital pathophysiological processes proven to contribute to vascular aging, and also lead to changes in levels of associated circulating molecules. Many of these molecules are consequently recognized as markers of vascular impairment and accelerated vascular aging in clinical and research settings, however, for these molecules to be classified as biomarkers of vascular aging, further criteria must be met. In this paper, we conducted a scoping literature review identifying thirty of the most important, and eight less important, biomarkers of vascular aging. Herein, we overview a selection of the most important molecules connected with the above-mentioned pathological conditions and study their usefulness as circulating biomarkers of vascular aging.
Collapse
Affiliation(s)
- Kristina R. Gopcevic
- Laboratory for Analytics of Biomolecules, Department of Chemistry in Medicine, Faculty of Medicine, Belgrade, Serbia
| | - Eugenia Gkaliagkousi
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - János Nemcsik
- Department of Family Medicine, Semmelweis University, Budapest, Hungary
- Health Service of ZUGLO, Department of Family Medicine, Budapest, Hungary
| | - Ömür Acet
- Vocational School of Health Science, Pharmacy Services Program, Tarsus University, Tarsus, Turkey
| | - M. Rosa Bernal-Lopez
- Internal Medicine Department, Regional University Hospital of Malaga, Instituto de Investigacion Biomedica de Malaga, University of Malaga, CIBER Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Málaga, Spain
| | - Rosa M. Bruno
- Unversite de Paris, INSERM, U970, Paris Cardiovascular Research Center, Paris, France
| | - Rachel E. Climie
- Unversite de Paris, INSERM, U970, Paris Cardiovascular Research Center, Paris, France
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
- Sports Cardiology Lab, Clinical Research Domain, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Nikolaos Fountoulakis
- Faculty of Life Sciences and Medicine, King’s College London - Waterloo Campus, London, United Kingdom
| | - Emil Fraenkel
- 1st Department of Internal Medicine, University Hospital and Pavol Jozef Šafárik University in Košice, Košice, Slovakia
| | - Antonios Lazaridis
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Petras Navickas
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Keith D. Rochfort
- School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland
| | - Agnė Šatrauskienė
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Centre of Cardiology and Angiology, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Jūratė Zupkauskienė
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
| | - Dimitrios Terentes-Printzios
- First Department of Cardiology, Hippokration Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
18
|
Goldman JM, Kim S, Narburgh S, Armitage BA, Schneider JW. Rapid, multiplexed detection of the let-7 miRNA family using γPNA amphiphiles in micelle-tagging electrophoresis. Biopolymers 2021; 113:e23479. [PMID: 34643943 DOI: 10.1002/bip.23479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 10/03/2021] [Accepted: 10/04/2021] [Indexed: 11/10/2022]
Abstract
miRNA is a promising class of biomarkers whose levels can be assayed to detect various forms of cancer and other serious diseases. These short, noncoding nucleic acids are difficult to detect due to their low abundance and the marginal stability of their duplexes with DNA probes. In addition, miRNAs within the same family have high sequence homology, and often, related miRNA differ in sequence by only a single base. In this report, we demonstrate an independent detection seven members of the let-7 family of miRNA in a single run. Key to success is the use of mini-PEG-substituted PNA amphiphiles (γPNAA) and highly fluorescent DNA nanotags in micelle tagging electrophoresis (MTE). Multiplexed detection is accomplished in capillary electrophoresis (CE) using oligomeric nanotags of pre-programmed lengths where the presence of a specific miRNA links its nanotag to a micelle drag-tag, which shifts the nanotag elution time to a defined region for detection. We further demonstrate that the peak shape and elution time are unaffected by the presence of up to 10 mg/ml of serum protein in the sample, with a total runtime of less than 4 min and a LOD of 10-100 pM. We discuss efforts to substantially decrease the detection limit using nanotags that are >1000 bp in length.
Collapse
Affiliation(s)
- Johnathan M Goldman
- Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
| | - Soyoung Kim
- Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
| | - Sarah Narburgh
- Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
| | - Bruce A Armitage
- Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
| | - James W Schneider
- Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
19
|
The Role of Oxidative Stress and the Importance of miRNAs as Potential Biomarkers in the Development of Age-Related Macular Degeneration. Processes (Basel) 2021. [DOI: 10.3390/pr9081328] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries. With the progressive aging of the population, AMD is a significant ophthalmological problem in the population over 50 years of age. The etiology of AMD is known to be based on various biochemical, immunological and molecular pathways and to be influenced by a range of genetic and environmental elements. This review provides an overview of the pathophysiological role of oxidative stress and free radicals in the retina with a special focus on the DNA repair efficiency and enzymatic antioxidant defense. It also presents a correlation between miRNA profile and AMD, and indicates their involvement in inflammation, angiogenesis, increased oxidation of cellular components, enzymatic antioxidant capacity and DNA repair efficiency, which play particularly important roles in AMD pathogenesis. Gene silencing by miRNAs can induce changes in antioxidant enzymes, leading to a complex interplay between redox imbalance by free radicals and miRNAs in modulating cellular redox homeostasis.
Collapse
|
|
20
|
Róka B, Tod P, Kaucsár T, Bukosza ÉN, Vörös I, Varga ZV, Petrovich B, Ágg B, Ferdinandy P, Szénási G, Hamar P. Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice. Biomedicines 2021; 9:biomedicines9070815. [PMID: 34356879 PMCID: PMC8301422 DOI: 10.3390/biomedicines9070815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 07/06/2021] [Accepted: 07/08/2021] [Indexed: 12/12/2022] Open
Abstract
(1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim was to identify microRNAs (miRNA/miR) involved in this process. (2) Methods: NMRI mice were subjected to 30 min of renal IR and one week later to Nx/sham surgery. The experiments were conducted for 7-28 days after IR. On day 8, multiplex renal miRNA profiling was performed. Expression of nine miRNAs was determined with qPCR at all time points. Based on the target prediction, plexin-A2 and Cd2AP were measured by Western blot. (3) Results: On day 8 after IR, the expression of 20/1195 miRNAs doubled, and 9/13 selected miRNAs were upregulated at all time points. Nx reduced the expression of several ischemia-induced pro-fibrotic miRNAs (fibromirs), such as miR-142a-duplex, miR-146a-5p, miR-199a-duplex, miR-214-3p and miR-223-3p, in the injured kidneys at various time points. Plexin-A2 was upregulated by IR on day 10, while Cd2AP was unchanged. (4) Conclusion: Nx delayed fibrosis progression and decreased the expression of ischemia-induced fibromirs. The protein expression of plexin-A2 and Cd2AP is mainly regulated by factors other than miRNAs.
Collapse
Affiliation(s)
- Beáta Róka
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (B.R.); (P.T.); (T.K.); (É.N.B.); (G.S.)
| | - Pál Tod
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (B.R.); (P.T.); (T.K.); (É.N.B.); (G.S.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
| | - Tamás Kaucsár
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (B.R.); (P.T.); (T.K.); (É.N.B.); (G.S.)
| | - Éva Nóra Bukosza
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (B.R.); (P.T.); (T.K.); (É.N.B.); (G.S.)
| | - Imre Vörös
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary; (I.V.); (Z.V.V.); (B.P.); (B.Á.); (P.F.)
- HCEMM-SU Cardiometabolic Immunology Research Group, Semmelweis University, 1089 Budapest, Hungary
| | - Zoltán V. Varga
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary; (I.V.); (Z.V.V.); (B.P.); (B.Á.); (P.F.)
- HCEMM-SU Cardiometabolic Immunology Research Group, Semmelweis University, 1089 Budapest, Hungary
| | - Balázs Petrovich
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary; (I.V.); (Z.V.V.); (B.P.); (B.Á.); (P.F.)
| | - Bence Ágg
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary; (I.V.); (Z.V.V.); (B.P.); (B.Á.); (P.F.)
- Pharmahungary Group, 6722 Szeged, Hungary
| | - Péter Ferdinandy
- Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary; (I.V.); (Z.V.V.); (B.P.); (B.Á.); (P.F.)
- Pharmahungary Group, 6722 Szeged, Hungary
| | - Gábor Szénási
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (B.R.); (P.T.); (T.K.); (É.N.B.); (G.S.)
| | - Péter Hamar
- Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary; (B.R.); (P.T.); (T.K.); (É.N.B.); (G.S.)
- Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary
- Correspondence: ; Tel.: +36-20-825-9751
| |
Collapse
|
|
21
|
The Multifaceted Role and Utility of MicroRNAs in Indolent B-Cell Non-Hodgkin Lymphomas. Biomedicines 2021; 9:biomedicines9040333. [PMID: 33806113 PMCID: PMC8064455 DOI: 10.3390/biomedicines9040333] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/14/2021] [Accepted: 03/18/2021] [Indexed: 02/07/2023] Open
Abstract
Normal B-cell development is a tightly regulated complex procedure, the deregulation of which can lead to lymphomagenesis. One common group of blood cancers is the B-cell non-Hodgkin lymphomas (NHLs), which can be categorized according to the proliferation and spread rate of cancer cells into indolent and aggressive ones. The most frequent indolent B-cell NHLs are follicular lymphoma and marginal zone lymphoma. MicroRNAs (miRNAs) are small non-coding RNAs that can greatly influence protein expression. Based on the multiple interactions among miRNAs and their targets, complex networks of gene expression regulation emerge, which normally are essential for proper B-cell development. Multiple miRNAs have been associated with B-cell lymphomas, as the deregulation of these complex networks can lead to such pathological states. The aim of the present review is to summarize the existing information regarding the multifaceted role of miRNAs in indolent B-cell NHLs, affecting the main B-cell subpopulations. We attempt to provide insight into their biological function, the complex miRNA-mRNA interactions, and their biomarker utility in these malignancies. Lastly, we address the limitations that hinder the investigation of the role of miRNAs in these lymphomas and discuss ways that these problems could be overcome in the future.
Collapse
|
|
22
|
Šatrauskienė A, Navickas R, Laucevičius A, Krilavičius T, Užupytė R, Zdanytė M, Ryliškytė L, Jucevičienė A, Holvoet P. Mir-1, miR-122, miR-132, and miR-133 Are Related to Subclinical Aortic Atherosclerosis Associated with Metabolic Syndrome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18041483. [PMID: 33557426 PMCID: PMC7915826 DOI: 10.3390/ijerph18041483] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 01/29/2021] [Accepted: 02/01/2021] [Indexed: 01/08/2023]
Abstract
Previously, miR-1, miR-122, miR-126, miR-132, miR-133, and miR-370 were found to be related to coronary artery disease (CAD) progression. However, their relationship with subclinical atherosclerosis, especially in subjects with metabolic syndrome, is unknown. Therefore, our aim was to determine their relationship with arterial markers of subclinical atherosclerosis. Metabolic syndrome subjects (n = 182) with high cardiovascular risk but without overt cardiovascular disease (CVD) were recruited from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program. The ardio-ankle vascular index (CAVI), augmentation index normalized to a heart rate of 75 bpm (AIxHR75), aortic pulse wave velocity (AoPWV), and carotid artery stiffness were assessed. MicroRNAs (miRs) were analyzed in serum. Pearson correlation and a univariate linear regression t-test showed that miR-1, miR-133b, and miR-133a were negatively associated with CAVI mean, whereas miR-122 was positively associated. MiR-1, miR-133b and miR-133a, and miR-145 were negatively associated with AIxHR75. MiR-122 correlated negatively with AoPWV. In multivariate linear regression models, miR-133b and miR-122 predicted CAVImean, miR-133 predicted AIxHR75, and miR-122 predicted AoPWV. MiR-132 predicted right carotid artery stiffness, and miR-1 predicted left carotid artery stiffness. The addition of smoking to miR-133b and miR-122 enhanced the prediction of CAVI. Age and triglycerides enhanced the prediction of AoPWV by miR-122. A cluster of four miRs are related to subclinical atherosclerosis in subjects with metabolic syndrome. Combined, they may have a more substantial diagnostic or prognostic value than any single miR. Future follow-up studies are needed to establish their clinical relevance.
Collapse
Affiliation(s)
- Agnė Šatrauskienė
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania; (A.Š.); (A.L.); (L.R.); (A.J.)
- Centre of Cardiology and Angiology, Vilnius University Hospital, Santaros Klinikos, 08410 Vilnius, Lithuania
| | - Rokas Navickas
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania; (A.Š.); (A.L.); (L.R.); (A.J.)
- Centre of Cardiology and Angiology, Vilnius University Hospital, Santaros Klinikos, 08410 Vilnius, Lithuania
- Correspondence:
| | - Aleksandras Laucevičius
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania; (A.Š.); (A.L.); (L.R.); (A.J.)
- Centre of Cardiology and Angiology, Vilnius University Hospital, Santaros Klinikos, 08410 Vilnius, Lithuania
- Experimental, Preventive, and Clinic Medicine Department, Centre for Innovative Medicine, 08406 Vilnius, Lithuania
| | - Tomas Krilavičius
- Informatics Faculty, Vytautas Magnus University, 44248 Kaunas, Lithuania; (T.K.); (R.U.)
- Baltic Institute of Advanced Technology, 01124 Vilnius, Lithuania
| | - Rūta Užupytė
- Informatics Faculty, Vytautas Magnus University, 44248 Kaunas, Lithuania; (T.K.); (R.U.)
- Baltic Institute of Advanced Technology, 01124 Vilnius, Lithuania
- Faculty of Mathematics and Informatics, Vilnius University, 03225 Vilnius, Lithuania
| | - Monika Zdanytė
- Department of Cardiology and Cardiovascular Medicine, Universität Tübingen, 72074 Tübingen, Germany;
| | - Ligita Ryliškytė
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania; (A.Š.); (A.L.); (L.R.); (A.J.)
- Centre of Cardiology and Angiology, Vilnius University Hospital, Santaros Klinikos, 08410 Vilnius, Lithuania
| | - Agnė Jucevičienė
- Clinic of Cardiac and Vascular Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 08661 Vilnius, Lithuania; (A.Š.); (A.L.); (L.R.); (A.J.)
- Centre of Cardiology and Angiology, Vilnius University Hospital, Santaros Klinikos, 08410 Vilnius, Lithuania
| | - Paul Holvoet
- Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, Belgium;
| |
Collapse
|
|
23
|
Mehta P. MicroRNA research: The new dawn of Tuberculosis. Indian J Tuberc 2020; 68:321-329. [PMID: 34099196 DOI: 10.1016/j.ijtb.2020.11.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 11/20/2020] [Indexed: 11/17/2022]
Abstract
Tuberculosis (TB) is global, one of the most fatal communicable diseases and leading cause of worldwide mortality. One-third of the global population is latently affected by Mtb (Mycobacterium tuberculosis) due to its ability to circumvent the host's immune response for its own survival. MicroRNAs (miRNAs) are small, non-coding RNAs which function at the post-transcriptional level and are critical in fine-tuning immune responses regulating the repertoire of genes expressed in immune cells. Recent studies have established their crucial role against TB. Furthermore, the differential expression pattern of miRNAs has revealed the potential role of miRNAs as biomarkers which could be utilized to differentiate between healthy controls and active TB patients or between active and latent TB. The recent advancements made in the field of miRNA regulation of the host responses against TB, as well as the potential of miRNAs as biomarkers for TB diagnosis are discussed here in this review.
Collapse
Affiliation(s)
- Priyanka Mehta
- Immunobiology Laboratory, Department of Zoology, University of Delhi, Delhi, 110 007, India.
| |
Collapse
|
|
24
|
Potential role of microRNAs in the treatment and diagnosis of cervical cancer. Cancer Genet 2020; 248-249:25-30. [DOI: 10.1016/j.cancergen.2020.09.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 08/01/2020] [Accepted: 09/20/2020] [Indexed: 12/23/2022]
|
|
25
|
Kolenda T, Guglas K, Baranowski D, Sobocińska J, Kopczyńska M, Teresiak A, Bliźniak R, Lamperska K. cfRNAs as biomarkers in oncology - still experimental or applied tool for personalized medicine already? Rep Pract Oncol Radiother 2020; 25:783-792. [PMID: 32904167 PMCID: PMC7451588 DOI: 10.1016/j.rpor.2020.07.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 02/13/2020] [Accepted: 07/31/2020] [Indexed: 02/07/2023] Open
Abstract
Currently, the challenges of contemporary oncology are focused mainly on the development of personalized medicine and precise treatment, which could be achieved through the use of molecular biomarkers. One of the biological molecules with great potential are circulating free RNAs (cfRNAs) which are present in various types of body fluids, such as blood, serum, plasma, and saliva. Also, different types of cfRNA particles can be distinguished depending on their length and function: microRNA (miRNA), PIWI-interacting RNA (piRNA), tRNA-derived RNA fragments (tRFs), circular RNA (circRNA), long non-coding RNA (lncRNA), and messenger RNA (mRNA). Moreover, cfRNAs occur in various forms: as a free molecule alone, in membrane vesicles, such as exosomes, or in complexes with proteins and lipids. One of the modern approaches for monitoring patient's condition is a "liquid biopsy" that provides a non-invasive and easily available source of circulating RNAs. Both the presence of specific cfRNA types as well as their concentration are dependent on many factors including cancer type or even reaction to treatment. Despite the possibility of using circulating free RNAs as biomarkers, there is still a lack of validated diagnostic panels, defined protocols for sampling, storing as well as detection methods. In this work we examine different types of cfRNAs, evaluate them as possible biomarkers, and analyze methods of their detection. We believe that further research on cfRNA and defining diagnostic panels could lead to better and faster cancer identification and improve treatment monitoring.
Collapse
Affiliation(s)
- Tomasz Kolenda
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
| | - Kacper Guglas
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
- Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warszawa, Poland
| | - Dawid Baranowski
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
| | - Joanna Sobocińska
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
| | - Magda Kopczyńska
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Teresiak
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
| | - Renata Bliźniak
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
| | | |
Collapse
|
|
26
|
Liu K, Tong H, Li T, Wang X, Chen Y. Research progress in molecular biology related quantitative methods of MicroRNA. Am J Transl Res 2020; 12:3198-3211. [PMID: 32774694 PMCID: PMC7407681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Accepted: 06/02/2020] [Indexed: 06/11/2023]
Abstract
MicroRNAs (miRNAs) are small RNAs of 18-25 nucleotides in length that are widely distributed in eukaryotes and are produced by DNA transcription. As regulators of post-transcriptional gene expression, it plays an important role in the physiological processes of cells. As some miRNAs in the body are abnormally expressed at different and earlier stages of diseases, this phenomenon suggests that accurate, sensitive and specifical detection of them can be helpful for early and differential diagnosis. To expound the technological progress of miRNA detection, we reviewed all the related articles in PubMed database published before May 6, 2019, with the following keywords: "miRNA", "real-time fluorescent quantitative PCR", "electrochemical detection", "next-generation sequencing", "digital PCR technology". Original articles and reviews on the topics were selected. The present methods established for quantitative detection of miRNAs mainly relies on various probe design and labeling techniques, and the improvement of the sensitivity and specificity of detection is often through combination of microarray chips, real-time fluorescent quantitative PCR, high-throughput sequencing and other techniques. This paper combines the existing microRNA detection methods to provide a reference for researchers to choose the best detection method.
Collapse
Affiliation(s)
- Kangsheng Liu
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care HospitalNanjing 210029, Jiangsu, China
| | - Hua Tong
- Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care HospitalNanjing 210029, Jiangsu, China
| | - Taiping Li
- Department of Neuro-Psychiatric Institute, The affiliated Brain Hospital Nanjing Medical UniversityNanjing 210029, Jiangsu, China
| | - Xiangdong Wang
- Department of Laboratory Diagnosis, Nanjing Brain Hospital affiliated to Nanjing Medical UniversityNanjing 210029, Jiangsu, China
| | - Yajun Chen
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care HospitalNanjing 210029, Jiangsu, China
| |
Collapse
|
|
27
|
Abramovic I, Ulamec M, Katusic Bojanac A, Bulic-Jakus F, Jezek D, Sincic N. miRNA in prostate cancer: challenges toward translation. Epigenomics 2020; 12:543-558. [PMID: 32267174 DOI: 10.2217/epi-2019-0275] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based literature search was conducted with the last update in May 2019. After identifying critical variations in designs and protocols that undermined clear-cut evidence acquisition, and reliable translation into clinical practice, we propose guidelines for most critical steps that should be considered in future research of miRNA as biomarkers, especially in PCa.
Collapse
Affiliation(s)
- Irena Abramovic
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Monika Ulamec
- Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Ljudevit Jurak Clinical Department of Pathology & Cytology, University Clinical Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Department of Pathology, University of Zagreb, School of Dental Medicine & School of Medicine, Zagreb 10000, Croatia
| | - Ana Katusic Bojanac
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Floriana Bulic-Jakus
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Davor Jezek
- Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Department of Histology & Embryology, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| | - Nino Sincic
- Department of Medical Biology, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Group for Research on Epigenetic Biomarkers, University of Zagreb School of Medicine, Zagreb 10000, Croatia.,Scientific Centre of Excellence for Reproductive & Regenerative Medicine, University of Zagreb School of Medicine, Zagreb 10000, Croatia
| |
Collapse
|
|
28
|
Valihrach L, Androvic P, Kubista M. Circulating miRNA analysis for cancer diagnostics and therapy. Mol Aspects Med 2020; 72:100825. [DOI: 10.1016/j.mam.2019.10.002] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/01/2019] [Accepted: 10/07/2019] [Indexed: 12/12/2022]
|
|
29
|
Wang P, Liu Q, Zhao H, Bishop JO, Zhou G, Olson LK, Moore A. miR-216a-targeting theranostic nanoparticles promote proliferation of insulin-secreting cells in type 1 diabetes animal model. Sci Rep 2020; 10:5302. [PMID: 32210316 PMCID: PMC7093482 DOI: 10.1038/s41598-020-62269-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 03/06/2020] [Indexed: 11/30/2022] Open
Abstract
Aberrant expression of miRNAs in pancreatic islets is closely related to the development of type 1 diabetes (T1D). The aim of this study was to identify key miRNAs dysregulated in pancreatic islets during T1D progression and to develop a theranostic approach to modify their expression using an MRI-based nanodrug consisting of iron oxide nanoparticles conjugated to miRNA-targeting oligonucleotides in a mouse model of T1D. Isolated pancreatic islets were derived from NOD mice of three distinct age groups (3, 8 and 18-week-old). Total RNA collected from cultured islets was purified and global miRNA profiling was performed with 3D-Gene global miRNA microarray mouse chips encompassing all mouse miRNAs available on the Sanger miRBase V16. Of the miRNAs that were found to be differentially expressed across three age groups, we identified one candidate (miR-216a) implicated in beta cell proliferation for subsequent validation by RT-PCR. Alterations in miR-216a expression within pancreatic beta cells were also examined using in situ hybridization on the frozen pancreatic sections. For in vitro studies, miR-216a mimics/inhibitors were conjugated to iron oxide nanoparticles and incubated with beta cell line, βTC-6. Cell proliferation marker Ki67 was evaluated. Expression of the phosphatase and tensin homolog (PTEN), which is one of the direct targets of miR-216a, was analyzed using western blot. For in vivo study, the miR-216a mimics/inhibitors conjugated to the nanoparticles were injected into 12-week-old female diabetic Balb/c mice via pancreatic duct. The delivery of the nanodrug was monitored by in vivo MRI. Blood glucose of the treated mice was monitored post injection. Ex vivo histological analysis of the pancreatic sections included staining for insulin, PTEN and Ki67. miRNA microarray demonstrated that the expression of miR-216a in the islets from NOD mice significantly changed during T1D progression. In vitro studies showed that treatment with a miR-216a inhibitor nanodrug suppressed proliferation of beta cells and increased the expression of PTEN, a miR-216a target. In contrast, introduction of a mimic nanodrug decreased PTEN expression and increased beta cell proliferation. Animals treated in vivo with a mimic nanodrug had higher insulin-producing functionality compared to controls. These observations were in line with downregulation of PTEN and increase in beta cell proliferation in that group. Our studies demonstrated that miR-216a could serve as a potential therapeutic target for the treatment of diabetes. miR-216a-targeting theranostic nanodrugs served as exploratory tools to define functionality of this miRNA in conjunction with in vivo MR imaging.
Collapse
Affiliation(s)
- Ping Wang
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, Michigan, 48823, USA.
| | - Qiong Liu
- Department of Anatomy, Histology and Embryology, School of Basic Medical Science, Fudan University, Shanghai, 200032, China
| | - Hongwei Zhao
- Shanxi Medical University, Taiyuan, Shanxi, 030001, China
- Department of Gynecologic Oncology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi, 030013, China
| | - Jack Owen Bishop
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, Michigan, 48823, USA
- Department of Neuroscience, College of Natural Science, Michigan State University, East Lansing, Michigan, 48824, USA
| | - Guoli Zhou
- Biomedical Research Informatics Core, Clinical & Translational Sciences Institute, Michigan State University, East Lansing, Michigan, 48824, USA
| | - L Karl Olson
- Department of Physiology, College of Natural Science, Michigan State University, East Lansing, Michigan, 48824, USA
| | - Anna Moore
- Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, Michigan, 48823, USA.
| |
Collapse
|
|
30
|
Ruiz-Tagle C, Naves R, Balcells ME. Unraveling the Role of MicroRNAs in Mycobacterium tuberculosis Infection and Disease: Advances and Pitfalls. Infect Immun 2020; 88:e00649-19. [PMID: 31871103 PMCID: PMC7035921 DOI: 10.1128/iai.00649-19] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Tuberculosis (TB) is an infectious disease of extremely high epidemiological burden worldwide that is easily acquired through the inhalation of infected respiratory droplets. The complex pathogenesis of this infection spans from subjects never developing this disease despite intense exposure, to others in which immune containment fails catastrophically and severe or disseminated forms of disease ensue. In recent decades, microRNAs (miRNAs) have gained increasing attention due to their role as gene silencers and because of their altered expression in diverse human diseases, including some infections. Recent research regarding miRNAs and TB has revealed that the expression profile for particular miRNAs clearly changes upon Mycobacterium tuberculosis infection and also varies in the different stages of this disease. However, despite the growing number of studies-some of which have even proposed some miRNAs as potential biomarkers-methodological variations and key differences in relevant factors, such as sex and age, cell type analyzed, M. tuberculosis strain, and antimicrobial therapy status, strongly hinder the comparison of data. In this review, we summarize and discuss the literature and highlight the role of selected miRNAs that have specifically and more consistently been associated with M. tuberculosis infection, together with a discussion of the possible gene and immune regulation pathways involved.
Collapse
Affiliation(s)
- Cinthya Ruiz-Tagle
- Departamento de Enfermedades Infecciosas del Adulto, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Rodrigo Naves
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - María Elvira Balcells
- Departamento de Enfermedades Infecciosas del Adulto, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| |
Collapse
|
|
31
|
Yamamoto Y, Kondo S, Matsuzaki J, Esaki M, Okusaka T, Shimada K, Murakami Y, Enomoto M, Tamori A, Kato K, Aoki Y, Takizawa S, Sakamoto H, Niida S, Takeshita F, Ochiya T. Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver Disease. Hepatol Commun 2020; 4:284-297. [PMID: 32025611 PMCID: PMC6996324 DOI: 10.1002/hep4.1451] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 10/20/2019] [Indexed: 01/01/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. The high mortality rate in HCC is largely due to the difficulty of early detection. In this study, to improve patient outcomes, serum samples from 345 patients with HCC, 46 patients with chronic hepatitis (CH), 93 patients with liver cirrhosis (LC), and 1,033 healthy individuals were analyzed with microRNA (miRNA) microarrays. We investigated the diagnostic potential of circulating miRNAs in serum and developed a detection model of HCC, including early stage. A diagnostic model was constructed based on the expression levels of a combination of miRNAs in a discovery set. We selected 52 miRNAs that had altered expressions according to disease progression status, established the diagnostic model with a combination of eight miRNAs in the discovery set, and tested the model in a validation set. The diagnostic values for discriminating cancer from HCC at-risk control samples were as follows: area under the curve, 0.99; sensitivity, 97.7%; specificity, 94.7%. With this model, 98% of stage I HCC cases were detected; these results were much better than those observed from conventional methods. Conclusion: Circulating miRNAs could serve as biomarkers for the accurate detection of HCC. Because the diagnostic accuracy was maintained even in stage I, this may represent an accurate detection method even for early stage HCC.
Collapse
Affiliation(s)
- Yusuke Yamamoto
- Division of Molecular and Cellular MedicineNational Cancer Center Research InstituteTokyoJapan
| | - Shunsuke Kondo
- Department of Hepatobiliary and Pancreatic OncologyNational Cancer Center HospitalTokyoJapan
| | - Juntaro Matsuzaki
- Division of Molecular and Cellular MedicineNational Cancer Center Research InstituteTokyoJapan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic OncologyNational Cancer Center HospitalTokyoJapan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic SurgeryNational Cancer Center HospitalTokyoJapan
| | - Yoshiki Murakami
- Department of HepatologyGraduate School of MedicineOsaka City UniversityOsakaJapan
- Department of Molecular PathologyTokyo Medical UniversityTokyoJapan
| | - Masaru Enomoto
- Department of HepatologyGraduate School of MedicineOsaka City UniversityOsakaJapan
| | - Akihiro Tamori
- Department of HepatologyGraduate School of MedicineOsaka City UniversityOsakaJapan
| | - Ken Kato
- Department of Gastrointestinal OncologyNational Cancer Center HospitalTokyoJapan
| | - Yoshiaki Aoki
- Dynacom Co., Ltd.World Business Garden E25ChibaJapan
| | - Satoko Takizawa
- Division of Molecular and Cellular MedicineNational Cancer Center Research InstituteTokyoJapan
- Toray Industries, Inc.KamakuraJapan
| | - Hiromi Sakamoto
- Department of Biobank and Tissue ResourcesNational Cancer Center Research InstituteTokyoJapan
| | - Shumpei Niida
- Medical Genome CenterNational Center for Geriatrics and GerontologyObuJapan
| | - Fumitaka Takeshita
- Fundamental Innovative Oncology Core CenterNational Cancer Center Research InstituteTokyoJapan
| | - Takahiro Ochiya
- Division of Molecular and Cellular MedicineNational Cancer Center Research InstituteTokyoJapan
- Department of Molecular and Cellular Medicine, Institute of Medical ScienceTokyo Medical UniversityTokyoJapan
| |
Collapse
|
|
32
|
Raeisi F, Mahmoudi E, Dehghani-Samani M, Hosseini SSE, Ghahfarrokhi AM, Arshi A, Forghanparast K, Ghazanfari S. Differential Expression Profile of miR-27b, miR-29a, and miR-155 in Chronic Lymphocytic Leukemia and Breast Cancer Patients. MOLECULAR THERAPY-ONCOLYTICS 2020; 16:230-237. [PMID: 32123723 PMCID: PMC7037977 DOI: 10.1016/j.omto.2020.01.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 01/11/2020] [Indexed: 12/17/2022]
Abstract
Over the past decade, studies on microRNA (miRNA) and cancer quickly became known. miRNAs are small non-coding RNAs that play a vital role in regulation of gene expression. In the present study, the expression of miR-27b, miR-29a, and miR-155, their prognostic roles, and their potential targets in chronic lymphocytic leukemia (CLL) and breast cancer (BC) by qRT-PCR were investigated. In two case-control studies, qRT-PCR was used to analyze the peripheral blood serum of 15 CLL patients and tissue samples of 15 BC patients for the expression of miR-27b, miR-29a, and miR-155. miRNA expression levels were calculated using the qRT-PCR method. The results revealed a significant increase in the expression of all miRNAs in patients with BC and CLL compared with respective healthy groups (p < 0.001). In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (p < 0.05), miR-155 and miR-27b (p < 0.01), and miR-27b and miR-29a (p < 0.001). In CLL patients, a significant difference between expression of both miR-27b and miR-29a compared with expression of miR-155 (p < 0.001) was found. Furthermore, a significant association between miR-155 and prevascular invasion was found. Significantly, elevated circulating miRNAs were shown to be BC specific and could differentiate BC tissues from the controls. It was demonstrated that miRNAs used in this study and their expression profiles can be developed as biomarkers for early diagnosis and prognosis of CLL and BC. Further studies utilizing a larger test group of patients would provide identification of miRNAs as key players in intercellular interactions.
Collapse
Affiliation(s)
- Farzaneh Raeisi
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.,Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Esmaeil Mahmoudi
- Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Mina Dehghani-Samani
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | | | - Ameneh Mehri Ghahfarrokhi
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Asghar Arshi
- Young Researchers and Elite Club, Najafabad Branch, Islamic Azad University, Najafabad, Iran
| | - Kayvan Forghanparast
- Canoga Park Urgent Care Family Medicine, 20905 Sherman Way, Canoga Park, CA 91303, USA
| | - Samaneh Ghazanfari
- Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, Geleen, The Netherlands.,Department of Biohybrid & Medical Textiles (Biotex), RWTH Aachen University, Aachen, Germany
| |
Collapse
|
|
33
|
Condrat CE, Thompson DC, Barbu MG, Bugnar OL, Boboc A, Cretoiu D, Suciu N, Cretoiu SM, Voinea SC. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells 2020; 9:E276. [PMID: 31979244 PMCID: PMC7072450 DOI: 10.3390/cells9020276] [Citation(s) in RCA: 816] [Impact Index Per Article: 163.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/14/2020] [Accepted: 01/21/2020] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.
Collapse
Affiliation(s)
- Carmen Elena Condrat
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Dana Claudia Thompson
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Madalina Gabriela Barbu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Oana Larisa Bugnar
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Andreea Boboc
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
| | - Dragos Cretoiu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
| | - Nicolae Suciu
- Alessandrescu-Rusescu National Institute for Mother and Child Health, Fetal Medicine Excellence Research Center, 020395 Bucharest, Romania; (C.E.C.); (D.C.T.); (M.G.B.); (O.L.B.); (A.B.); (D.C.); (N.S.)
- Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
- Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, 020395 Bucharest, Romania
| | - Sanda Maria Cretoiu
- Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474 Bucharest, Romania
| | - Silviu Cristian Voinea
- Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, 252 Fundeni Rd., 022328 Bucharest, Romania;
| |
Collapse
|
|
34
|
Bajan S, Hutvagner G. RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs. Cells 2020; 9:E137. [PMID: 31936122 PMCID: PMC7016530 DOI: 10.3390/cells9010137] [Citation(s) in RCA: 260] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 12/23/2019] [Accepted: 12/30/2019] [Indexed: 02/07/2023] Open
Abstract
The first therapeutic nucleic acid, a DNA oligonucleotide, was approved for clinical use in 1998. Twenty years later, in 2018, the first therapeutic RNA-based oligonucleotide was United States Food and Drug Administration (FDA) approved. This promises to be a rapidly expanding market, as many emerging biopharmaceutical companies are developing RNA interference (RNAi)-based, and RNA-based antisense oligonucleotide therapies. However, miRNA therapeutics are noticeably absent. miRNAs are regulatory RNAs that regulate gene expression. In disease states, the expression of many miRNAs is measurably altered. The potential of miRNAs as therapies and therapeutic targets has long been discussed and in the context of a wide variety of infections and diseases. Despite the great number of studies identifying miRNAs as potential therapeutic targets, only a handful of miRNA-targeting drugs (mimics or inhibitors) have entered clinical trials. In this review, we will discuss whether the investment in finding potential miRNA therapeutic targets has yielded feasible and practicable results, the benefits and obstacles of miRNAs as therapeutic targets, and the potential future of the field.
Collapse
Affiliation(s)
- Sarah Bajan
- Faculty of Science, University of Technology Sydney, Sydney, NSW 2000, Australia
- Health and Sport Science, University of Sunshine Coast, Sunshine Coast, QLD 4556, Australia
| | - Gyorgy Hutvagner
- School of Biomedical Engineering Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW 2000, Australia
| |
Collapse
|
|
35
|
Soda N, Rehm BHA, Sonar P, Nguyen NT, Shiddiky MJA. Advanced liquid biopsy technologies for circulating biomarker detection. J Mater Chem B 2019; 7:6670-6704. [PMID: 31646316 DOI: 10.1039/c9tb01490j] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liquid biopsy is a new diagnostic concept that provides important information for monitoring and identifying tumor genomes in body fluid samples. Detection of tumor origin biomolecules like circulating tumor cells (CTCs), circulating tumor specific nucleic acids (circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), microRNAs (miRNAs), long non-coding RNAs (lnRNAs)), exosomes, autoantibodies in blood, saliva, stool, urine, etc. enables cancer screening, early stage diagnosis and evaluation of therapy response through minimally invasive means. From reliance on painful and hazardous tissue biopsies or imaging depending on sophisticated equipment, cancer management schemes are witnessing a rapid evolution towards minimally invasive yet highly sensitive liquid biopsy-based tools. Clinical application of liquid biopsy is already paving the way for precision theranostics and personalized medicine. This is achieved especially by enabling repeated sampling, which in turn provides a more comprehensive molecular profile of tumors. On the other hand, integration with novel miniaturized platforms, engineered nanomaterials, as well as electrochemical detection has led to the development of low-cost and simple platforms suited for point-of-care applications. Herein, we provide a comprehensive overview of the biogenesis, significance and potential role of four widely known biomarkers (CTCs, ctDNA, miRNA and exosomes) in cancer diagnostics and therapeutics. Furthermore, we provide a detailed discussion of the inherent biological and technical challenges associated with currently available methods and the possible pathways to overcome these challenges. The recent advances in the application of a wide range of nanomaterials in detecting these biomarkers are also highlighted.
Collapse
Affiliation(s)
- Narshone Soda
- School of Environment and Science, Griffith University, Nathan Campus, QLD 4111, Australia. and Queensland Micro- and Nanotechnology Centre (QMNC), Griffith University, Nathan Campus, QLD 4111, Australia
| | - Bernd H A Rehm
- Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery (GRIDD), Griffith University, Nathan, QLD 4111, Australia
| | - Prashant Sonar
- School of Chemistry, Physics and Mechanical Engineering, Molecular Design and Synthesis, Queensland University of Technology (QUT), Brisbane, Australia
| | - Nam-Trung Nguyen
- Queensland Micro- and Nanotechnology Centre (QMNC), Griffith University, Nathan Campus, QLD 4111, Australia
| | - Muhammad J A Shiddiky
- School of Environment and Science, Griffith University, Nathan Campus, QLD 4111, Australia. and Queensland Micro- and Nanotechnology Centre (QMNC), Griffith University, Nathan Campus, QLD 4111, Australia
| |
Collapse
|
|
36
|
Meta-Analysis of Differential miRNA Expression after Bariatric Surgery. J Clin Med 2019; 8:jcm8081220. [PMID: 31443156 PMCID: PMC6723285 DOI: 10.3390/jcm8081220] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 08/09/2019] [Accepted: 08/12/2019] [Indexed: 02/06/2023] Open
Abstract
Bariatric surgery is an efficient treatment for weight loss in obese patients and for resolving obesity comorbidities. However, the mechanisms behind these outcomes are unclear. Recent studies have indicated significant alterations in the transcriptome after surgery, specifically in the differential expression of microRNAs. In order to summarize the recent findings, we conducted a systematic summary of studies comparing microRNA expression levels before and after surgery. We identified 17 animal model and human studies from four databases (Ovid, Scopus, Web of Science, and PubMed) to be enrolled in this meta-analysis. From these studies, we identified 14 miRNAs which had the same direction of modulation of their expression after surgery in at least two studies (downregulated: hsa-miR-93-5p, hsa-miR-106b-5p, hsa-let-7b-5p, hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-19b-3p, hsa-miR-92a-3p, hsa-miR-222-3p, hsa-miR-142-3p, hsa-miR-140-5p, hsa-miR-155-5p, rno-miR-320-3p; upregulated: hsa-miR-7-5p, hsa-miR-320c). Pathway analysis for these miRNAs was done using database resources (DIANA-TarBase and KEGG pathway database) and their predicted target genes were discussed in relation with obesity and its comorbidities. Discrepancies in study design, such as miRNA source, bariatric surgery type, time of observation after surgery, and miRNA profiling methods, were also discussed.
Collapse
|
|
37
|
Hashimoto K, Inada M, Ito K. Multiplex Real-Time Loop-Mediated Isothermal Amplification Using an Electrochemical DNA Chip Consisting of a Single Liquid-Flow Channel. Anal Chem 2019; 91:3227-3232. [PMID: 30734558 DOI: 10.1021/acs.analchem.8b05284] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
We developed a multiplex system capable of simultaneously quantifying different target sequences by applying an electrochemical DNA chip that consists of single liquid-flow channel with primers designed for loop-mediated isothermal amplification (LAMP). We applied this system for detecting mature microRNAs (miRNAs). miRNAs extracted from serum were enzymatically lengthened to about 100 base pairs by reverse-transcription and elongation reactions. The LAMP primers for amplifying the lengthened miRNAs were adsorbed and immobilized on the surface of the liquid-flow channel at five different positions. A LAMP solution containing the lengthened miRNAs, Tin DNA polymerase, and ruthenium hexaamine (RuHex) as a redox compound was injected into the DNA chip. The electrochemical reaction of RuHex in the LAMP solution was then measured continuously via linear-sweep voltammetry at 65 °C. The LAMP reaction of the positive control revealed that the cathodic peak current of RuHex increased. Additionally, the initial number of miRNA copies was correlated with the time when the cathodic current began to increase. Five miRNAs were simultaneously detected at 103-106 copies per 50 μL within 2 h. We expect these results will be useful for developing a simple and stable electrochemical-based method for the real-time monitoring of miRNAs, while also facilitating the implementation of electrochemical DNA chips for molecular analyses.
Collapse
Affiliation(s)
- Koji Hashimoto
- Corporate Research & Development Center, Research & Development Division , Toshiba Corporation , 1 Komukai-Toshiba-cho , Saiwai-ku, Kawasaki 212-8582 , Japan
| | - Mika Inada
- Corporate Research & Development Center, Research & Development Division , Toshiba Corporation , 1 Komukai-Toshiba-cho , Saiwai-ku, Kawasaki 212-8582 , Japan
| | - Keiko Ito
- Corporate Research & Development Center, Research & Development Division , Toshiba Corporation , 1 Komukai-Toshiba-cho , Saiwai-ku, Kawasaki 212-8582 , Japan
| |
Collapse
|
|
38
|
Picard-Meyer E, Peytavin de Garam C, Schereffer JL, Robardet E, Cliquet F. Evaluation of six TaqMan RT-rtPCR kits on two thermocyclers for the reliable detection of rabies virus RNA. J Vet Diagn Invest 2018; 31:47-57. [PMID: 30541405 DOI: 10.1177/1040638718818223] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Rabies is diagnosed postmortem in animals, based on tests prescribed by the World Organization for Animal Health (OIE), such as the fluorescent antibody test, the direct rapid immunohistochemistry test, or pan-lyssavirus PCR assays. Several reverse-transcription real-time PCR (RT-rtPCR) methods have been developed and validated for rapid and accurate detection of lyssaviruses. We evaluated the performance of 6 TaqMan RT-rtPCR kits using different commercial master mixes and 2 real-time thermocyclers. Changing the master mix overall did not influence the TaqMan RT-rtPCR performance, regardless of the thermocycler used. The limits of detection at the 95% confidence level were 18.1-25.8 copies/µL for the Rotor-Gene Q MDx thermocycler and 16.7-21.5 for the Mx3005P thermocycler. Excellent repeatability was demonstrated for rabies virus (RABV) RNA samples of 100, 50, and 25 copies/µL regardless of the thermocycler used. RABV field samples ( n = 35) isolated worldwide gave positive results using the most efficient of the 6 kits tested, with a copy number of 6.03 × 102 to 6.78 × 107 RNA copies per reaction. The TaqMan RT-rtPCR assay provides sensitive and rapid amplification of RABV RNA.
Collapse
Affiliation(s)
| | | | | | | | - Florence Cliquet
- ANSES Nancy Laboratory for Rabies and Wildlife, Malzéville, France
| |
Collapse
|
|
39
|
Singh RD, Shandilya R, Bhargava A, Kumar R, Tiwari R, Chaudhury K, Srivastava RK, Goryacheva IY, Mishra PK. Quantum Dot Based Nano-Biosensors for Detection of Circulating Cell Free miRNAs in Lung Carcinogenesis: From Biology to Clinical Translation. Front Genet 2018; 9:616. [PMID: 30574163 PMCID: PMC6291444 DOI: 10.3389/fgene.2018.00616] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 11/23/2018] [Indexed: 12/24/2022] Open
Abstract
Lung cancer is the most frequently occurring malignancy and the leading cause of cancer-related death for men in our country. The only recommended screening method is clinic based low-dose computed tomography (also called a low-dose CT scan, or LDCT). However, the effect of LDCT on overall mortality observed in lung cancer patients is not statistically significant. Over-diagnosis, excessive cost, risks associated with radiation exposure, false positive results and delay in the commencement of the treatment procedure questions the use of LDCT as a reliable technique for population-based screening. Therefore, identification of minimal-invasive biomarkers able to detect malignancies at an early stage might be useful to reduce the disease burden. Circulating nucleic acids are emerging as important source of information for several chronic pathologies including lung cancer. Of these, circulating cell free miRNAs are reported to be closely associated with the clinical outcome of lung cancer patients. Smaller size, sequence homology between species, low concentration and stability are some of the major challenges involved in characterization and specific detection of miRNAs. To circumvent these problems, synthesis of a quantum dot based nano-biosensor might assist in sensitive, specific and cost-effective detection of differentially regulated miRNAs. The wide excitation and narrow emission spectra of these nanoparticles result in excellent fluorescent quantum yields with a broader color spectrum which make them ideal bio-entities for fluorescence resonance energy transfer (FRET) based detection for sequential or simultaneous study of multiple targets. In addition, photo-resistance and higher stability of these nanoparticles allows extensive exposure and offer state-of-the art sensitivity for miRNA targeting. A major obstacle for integrating QDs into clinical application is the QD-associated toxicity. However, the use of non-toxic shells along with surface modification not only overcomes the toxicity issues, but also increases the ability of QDs to quickly detect circulating cell free miRNAs in a non-invasive mode. The present review illustrates the importance of circulating miRNAs in lung cancer diagnosis and highlights the translational prospects of developing QD-based nano-biosensor for rapid early disease detection.
Collapse
Affiliation(s)
- Radha D. Singh
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Ruchita Shandilya
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Arpit Bhargava
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Rajat Kumar
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Rajnarayan Tiwari
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| | - Koel Chaudhury
- School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, India
| | - Rupesh K. Srivastava
- Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India
| | - Irina Y. Goryacheva
- Department of General and Inorganic Chemistry, Saratov State University, Saratov, Russia
| | - Pradyumna K. Mishra
- Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India
| |
Collapse
|
|
40
|
Liu CH, Ampuero J, Gil-Gómez A, Montero-Vallejo R, Rojas Á, Muñoz-Hernández R, Gallego-Durán R, Romero-Gómez M. miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. J Hepatol 2018; 69:1335-1348. [PMID: 30142428 DOI: 10.1016/j.jhep.2018.08.008] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 07/21/2018] [Accepted: 08/07/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS microRNAs (miRNAs) are deregulated in non-alcoholic fatty liver disease (NAFLD) and have been proposed as useful markers for the diagnosis and stratification of disease severity. We conducted a meta-analysis to identify the potential usefulness of miRNA biomarkers in the diagnosis and stratification of NAFLD severity. METHODS After a systematic review, circulating miRNA expression consistency and mean fold-changes were analysed using a vote-counting strategy. The sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and area under the curve (AUC) for the diagnosis of NAFLD or non-alcoholic steatohepatitis (NASH) were pooled using a bivariate meta-analysis. Deeks' funnel plot was used to assess the publication bias. RESULTS Thirty-seven studies of miRNA expression profiles and six studies of diagnostic accuracy were ultimately included in the quantitative analysis. miRNA-122 and miRNA-192 showed consistent upregulation. miRNA-122 was upregulated in every scenario used to distinguish NAFLD severity. The miRNA expression correlation between the serum and liver tissue was inconsistent across studies. miRNA-122 distinguished NAFLD from healthy controls with an AUC of 0.82 (95% CI 0.75-0.89), and miRNA-34a distinguished non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver (NAFL) with an AUC of 0.78 (95% CI 0.67-0.88). CONCLUSION miRNA-34a, miRNA-122 and miRNA-192 were identified as potential diagnostic markers to segregate NAFL from NASH. Both miRNA-122, in distinguishing NAFLD from healthy controls, and miRNA-34a, in distinguishing NASH from NAFL, showed moderate diagnostic accuracy. miRNA-122 was upregulated in every scenario of NAFL, NASH and fibrosis. LAY SUMMARY: microRNAs are deregulated in non-alcoholic fatty liver disease. The microRNAs, miRNA-34a, miRNA-122 and miRNA-192, were identified as potential biomarkers of non-alcoholic fatty liver and non-alcoholic steatohepatitis, at different stages of disease severity. The correlation between miRNA expression in the serum and in liver tissue was inconsistent, or even inverse.
Collapse
Affiliation(s)
- Chang-Hai Liu
- Institute of Biomedicine of Seville, Sevilla, Spain; University of Seville, Seville, Spain
| | - Javier Ampuero
- Institute of Biomedicine of Seville, Sevilla, Spain; Unit of Digestive Diseases and Ciberehd, University Hospital Virgen del Rocío, Seville, Spain; University of Seville, Seville, Spain
| | - Antonio Gil-Gómez
- Institute of Biomedicine of Seville, Sevilla, Spain; University of Seville, Seville, Spain
| | - Rocío Montero-Vallejo
- Institute of Biomedicine of Seville, Sevilla, Spain; University of Seville, Seville, Spain
| | - Ángela Rojas
- Institute of Biomedicine of Seville, Sevilla, Spain
| | | | | | - Manuel Romero-Gómez
- Institute of Biomedicine of Seville, Sevilla, Spain; Unit of Digestive Diseases and Ciberehd, University Hospital Virgen del Rocío, Seville, Spain; University of Seville, Seville, Spain.
| |
Collapse
|
|
41
|
Gholaminejad A, Abdul Tehrani H, Gholami Fesharaki M. Identification of candidate microRNA biomarkers in diabetic nephropathy: a meta-analysis of profiling studies. J Nephrol 2018; 31:813-831. [PMID: 30019103 DOI: 10.1007/s40620-018-0511-5] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Accepted: 06/24/2018] [Indexed: 01/20/2023]
Abstract
AIMS The aim was to perform a meta-analysis on the miRNA expression profiling studies in diabetic nephropathy (DN) to identify candidate diagnostic biomarkers. METHODS A comprehensive literature search was done in several databases and 53 DN miRNA expression studies were selected. To identify significant DN-miR meta-signatures, two meta-analysis methods were employed: vote-counting strategy and the robust rank aggregation method. The targets of DN-miRs were obtained and a gene set enrichment analysis was carried out to identify the pathways most strongly affected by dysregulation of these miRNAs. RESULTS We identified a significant miRNA meta-signature common to both meta-analysis approaches of three up-regulated (miR-21-5p, miR-146a-5p, miR-10a-5p) and two down-regulated (miR-25-3p and miR-26a-5p) miRNAs. Besides that, subgroup analyses divided and compared the differentially expressed miRNAs according to species (human and animal), types of diabetes (T1DN and T2DN) and tissue types (kidney, blood and urine). Enrichment analysis confirmed that DN-miRs supportively target functionally related genes in signaling and community pathways in DN. CONCLUSION Five highly significant and consistently dysregulated miRNAs were identified, and future studies should focus on discovering their potential effect on DN and their clinical value as DN biomarkers and therapeutic mediators.
Collapse
Affiliation(s)
- Alieh Gholaminejad
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal Al Ahmad Street, No. 7, P.O. Box 14115-111, Tehran, Tehran Province, Iran
| | - Hossein Abdul Tehrani
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal Al Ahmad Street, No. 7, P.O. Box 14115-111, Tehran, Tehran Province, Iran.
| | | |
Collapse
|
|
42
|
Gholaminejad A, Abdul Tehrani H, Gholami Fesharaki M. Identification of candidate microRNA biomarkers in renal fibrosis: a meta-analysis of profiling studies. Biomarkers 2018; 23:713-724. [PMID: 29909697 DOI: 10.1080/1354750x.2018.1488275] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 05/24/2018] [Accepted: 06/08/2018] [Indexed: 12/26/2022]
Abstract
The prognostic, diagnostic and therapeutic value of microRNA (miRNA) expression aberrations in renal fibrosis has been studied in recent years. However, the miRNA expression profiling efforts have led to inconsistent results between the studies. The aim of this study was to perform a meta-analysis on the renal fibrosis miRNA expression profiling studies to identify candidate diagnostic biomarkers. We performed comprehensive literature searches in several databases to identify miRNA expression studies of renal fibrosis in animal models and humans. The miRNAs expression data were extracted from 20 included studies, and both miRNA vote-counting strategy and Robust Rank Aggregation method were utilized to identify significant miRNA meta-signatures. The predicted and validated targets of miRNA meta-signature were obtained by using MultiMiR package in 11 databases. Then a gene set enrichment analysis (KEGG, PANTHER pathways and GO processes) were carried out with GeneCodis web tool to recognize pathways that are most strongly influenced by modified expressions of these miRNAs. We recognized in both meta-analysis approaches a significant miRNA meta-signature of five up-regulated (miR-142-3p, miR-223-3p, miR-21-5p, miR-142-5p and miR-214-3p) and two down-regulated (miR-29c-3p and miR-200a-3p) miRNAs. Enrichment analysis confirmed that miRNA meta-signature cooperatively target functionally related genes in signalling and developmental pathways in renal fibrosis. This meta-analysis identified seven highly significant and consistently dysregulated miRNAs from 20 datasets, as the focus of future investigations to discover their potential influence to renal fibrosis and their clinical utility as biomarkers and/or as therapeutic mediators against chronic kidney disease..
Collapse
Affiliation(s)
- Alieh Gholaminejad
- a Department of Medical Biotechnology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran
| | - Hossein Abdul Tehrani
- a Department of Medical Biotechnology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran
| | | |
Collapse
|
|
43
|
Yokoi A, Matsuzaki J, Yamamoto Y, Yoneoka Y, Takahashi K, Shimizu H, Uehara T, Ishikawa M, Ikeda SI, Sonoda T, Kawauchi J, Takizawa S, Aoki Y, Niida S, Sakamoto H, Kato K, Kato T, Ochiya T. Integrated extracellular microRNA profiling for ovarian cancer screening. Nat Commun 2018; 9:4319. [PMID: 30333487 PMCID: PMC6192980 DOI: 10.1038/s41467-018-06434-4] [Citation(s) in RCA: 216] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 08/28/2018] [Indexed: 01/14/2023] Open
Abstract
A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer. Screening methods for early detection of ovarian cancer is technically difficult. Here, the authors investigated circulating microRNA in human blood serum and developed a model using 10 microRNAs to discern between ovarian cancer and being ovarian tumors, solid tumors, and non-cancer patients.
Collapse
Affiliation(s)
- Akira Yokoi
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 05-01-01 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.,Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Juntaro Matsuzaki
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 05-01-01 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yusuke Yamamoto
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 05-01-01 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Yutaka Yoneoka
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Kenta Takahashi
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Hanako Shimizu
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takashi Uehara
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Mitsuya Ishikawa
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shun-Ichi Ikeda
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takumi Sonoda
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 05-01-01 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Junpei Kawauchi
- New Frontiers Research Institute, Toray Industries, 6-10-1 Tebiro, Kamakura city, Kanagawa, 248-0036, Japan
| | - Satoko Takizawa
- New Frontiers Research Institute, Toray Industries, 6-10-1 Tebiro, Kamakura city, Kanagawa, 248-0036, Japan
| | - Yoshiaki Aoki
- Division of Bioinformatics, Dynacom Co., Ltd., World Business Garden E25, 2-6-1 Nakase, Mihama-ku, Chiba city, Chiba, 261-7125, Japan
| | - Shumpei Niida
- Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan
| | - Hiromi Sakamoto
- Department of Clinical Genomics, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, 104-0045, Japan
| | - Ken Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Tomoyasu Kato
- Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 05-01-01 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
| |
Collapse
|
|
44
|
High-throughput chemical screening to discover new modulators of microRNA expression in living cells by using graphene-based biosensor. Sci Rep 2018; 8:11413. [PMID: 30061704 PMCID: PMC6065314 DOI: 10.1038/s41598-018-29633-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2018] [Accepted: 07/16/2018] [Indexed: 12/30/2022] Open
Abstract
MicroRNAs (miRNAs) are important regulatory RNAs that control gene expression in various biological processes. Therefore, control over the disease-related miRNA expression is important both for basic research and for a new class of therapeutic modality to treat serious diseases such as cancer. Here, we present a high-throughput screening strategy to identify small molecules that modulate miRNA expression in living cells. The screen enables simultaneous monitoring of the phenotypic cellular changes associated with the miRNA expression by measuring quantitative fluorescent signals corresponding to target miRNA level in living cells based on a novel biosensor composed of peptide nucleic acid and nano-sized graphene oxide. In this study, the biosensor based cellular screening of 967 compounds (including FDA-approved drugs, enzyme inhibitors, agonists, and antagonists) in cells identified four different classes of small molecules consisting of (i) 70 compounds that suppress both miRNA-21 (miR-21) expression and cell proliferation, (ii) 65 compounds that enhance miR-21 expression and reduce cell proliferation, (iii) 2 compounds that suppress miR-21 expression and increase cell proliferation, and (iv) 21 compounds that enhance both miR-21 expression and cell proliferation. We further investigated the hit compounds to correlate cell morphology changes and cell migration ability with decreased expression of miR-21.
Collapse
|
|
45
|
Role of MicroRNAs in Renal Parenchymal Diseases-A New Dimension. Int J Mol Sci 2018; 19:ijms19061797. [PMID: 29914215 PMCID: PMC6032378 DOI: 10.3390/ijms19061797] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Revised: 06/07/2018] [Accepted: 06/08/2018] [Indexed: 11/18/2022] Open
Abstract
Since their discovery in 1993, numerous microRNAs (miRNAs) have been identified in humans and other eukaryotic organisms, and their role as key regulators of gene expression is still being elucidated. It is now known that miRNAs not only play a central role in the processes that ensure normal development and physiology, but they are often dysregulated in various diseases. In this review, we present an overview of the role of miRNAs in normal renal development and physiology, in maladaptive renal repair after injury, and in the pathogenesis of renal parenchymal diseases. In addition, we describe methods used for their detection and their potential as therapeutic targets. Continued research on renal miRNAs will undoubtedly improve our understanding of diseases affecting the kidneys and may also lead to new therapeutic agents.
Collapse
|
|
46
|
de Ronde MWJ, Ruijter JM, Moerland PD, Creemers EE, Pinto-Sietsma SJ. Study Design and qPCR Data Analysis Guidelines for Reliable Circulating miRNA Biomarker Experiments: A Review. Clin Chem 2018; 64:1308-1318. [PMID: 29903876 DOI: 10.1373/clinchem.2017.285288] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 05/08/2018] [Indexed: 01/07/2023]
Abstract
BACKGROUND In the past decade, the search for circulating microRNA (miRNA) biomarkers has yielded numerous associations between miRNAs and different types of disease. However, many of these relations could not be replicated in subsequent studies under similar experimental conditions. Although this lack of replicability may be explained by the variation in experimental design and analysis methods, guidelines on the most appropriate design and analysis methods to study circulating miRNAs are scarce. CONTENT miRNA biomarker experiments generally consist of a discovery phase and a validation phase. In the discovery phase, typically hundreds of miRNAs are measured in parallel to identify candidate biomarkers. Because of the costs of such high-throughput experiments, the number of individuals included in those studies is often too small, which can easily lead to false positives and false negatives. In the validation phase, a small number of identified biomarker candidates are measured in a large cohort of cases and controls, generally by quantitative PCR (qPCR). Although qPCR is a sensitive method to measure miRNAs in the circulation, experimental design and qPCR data analysis remain challenging. Omitting some crucial steps in the design and analysis of the qPCR experiment or performing them incorrectly can cause serious biases, ultimately leading to false conclusions. SUMMARY In this review, we aim to expose and discuss the most common sources of interstudy variation in miRNA research from a methodological point of view and to provide guidelines on how to perform these steps correctly to increase replicability of studies on circulating miRNAs.
Collapse
Affiliation(s)
- Maurice W J de Ronde
- Departments of Vascular Medicine.,Clinical Epidemiology, Biostatistics and Bioinformatics
| | | | | | - Esther E Creemers
- Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | | |
Collapse
|
|
47
|
Tölle A, Blobel CC, Jung K. Circulating miRNAs in blood and urine as diagnostic and prognostic biomarkers for bladder cancer: an update in 2017. Biomark Med 2018; 12:667-676. [PMID: 29896971 DOI: 10.2217/bmm-2017-0392] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
This study presents a critical appraisal of previously published study data of miRNAs in blood, urine and exosomes as biomarkers of bladder cancer (BC). The evaluation included 39 articles published from the beginning of 2010 until September 2017 and searched in PubMed. The heterogeneity of studies, due to their clinicopathological variability, including insufficient consideration of diagnostic and prognostic biomarker guidelines and missing internal and external validation of data, do not currently allow the recommending of a useful miRNA marker as diagnostic or prognostic tool in BC. Future multi-institutional studies are necessary to overcome the deficiencies in these studies in order to prove the usefulness of circulating miRNAs as robust biomarkers for BC.
Collapse
Affiliation(s)
- Angelika Tölle
- Department of Urology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.,CONGEN Biotechnology GmbH, 13125 Berlin, Germany
| | - Conrad C Blobel
- Department of Urology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany
| | - Klaus Jung
- Berlin Institute for Urologic Research, 10117 Berlin, Germany
| |
Collapse
|
|
48
|
Identification of miRNAs in cervical mucus as a novel diagnostic marker for cervical neoplasia. Sci Rep 2018; 8:7070. [PMID: 29728572 PMCID: PMC5935744 DOI: 10.1038/s41598-018-25310-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 04/18/2018] [Indexed: 01/17/2023] Open
Abstract
microRNAs (miRNAs) play important roles in regulation of gene expression during cervical carcinogenesis. We investigated expression profiles of miRNAs in cervical cancer and its precursor lesions by utilizing cervical mucus. Cervical mucus was collected from 230 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). The levels of miRNA in the mucus were quantified by miRNA array and real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The performance for detecting diseases was statistically analysed. The expression of miRNAs was further validated in the surgical tissues of enrolled patients. Four miRNAs (miR-126-3p, -20b-5p, -451a, and -144-3p) were significantly up-regulated in SCC and AD compared with normal, and their expression levels correlated with disease severity and high-risk human papillomavirus infection. Receiver operating characteristic curve analyses revealed that the area under the curve values for miR-126-3p, -20b-5p, -451a, and -144-3p were 0.89, 0.90, 0.94, and 0.93, respectively, for SCC plus AD compared with normal, showing high accuracy of cancer detection. Real-time RT-PCR analyses confirmed the expression of these four miRNAs in frozen tissues from cervical cancer. miR-126-3p, -20b-5p, -451a, and -144-3p in cervical mucus are promising biomarkers for cervical cancer and high-grade CINs.
Collapse
|
|
49
|
Lee JR, Appelmann I, Miething C, Shultz TO, Ruderman D, Kim D, Mallick P, Lowe SW, Wang SX. Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors. Theranostics 2018; 8:1389-1398. [PMID: 29507628 PMCID: PMC5835944 DOI: 10.7150/thno.20706] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 12/12/2017] [Indexed: 01/23/2023] Open
Abstract
Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays. Methods: Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice. Results: The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment. Conclusion: The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.
Collapse
Affiliation(s)
- Jung-Rok Lee
- Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, South Korea
| | - Iris Appelmann
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Cornelius Miething
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Internal Medicine, Medical Center - University of Freiburg, Freiburg, Germany
| | - Tyler O. Shultz
- Department of Materials Science and Engineering, Stanford University, Stanford, California, USA
| | - Daniel Ruderman
- Ellison Institute of Transformative Medicine of USC, USC Keck School of Medicine, Los Angeles, California, USA
| | - Dokyoon Kim
- Department of Materials Science and Engineering, Stanford University, Stanford, California, USA
| | - Parag Mallick
- Department of Medicine, Department of Radiology, Stanford University, Stanford, California, USA
| | - Scott W. Lowe
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Shan X. Wang
- Department of Materials Science and Engineering, Stanford University, Stanford, California, USA
- Department of Medicine, Department of Radiology, Stanford University, Stanford, California, USA
- Department of Electrical Engineering, Stanford University, Stanford, California, USA
| |
Collapse
|
|
50
|
Yin X, Liang L, Zhao P, Lan F, Zhang L, Ge S, Yu J. Double signal amplification based on palladium nanoclusters and nucleic acid cycles on a μPAD for dual-model detection of microRNAs. J Mater Chem B 2018; 6:5795-5801. [DOI: 10.1039/c8tb01552j] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Dual-model signal outputs and double signal amplification on the platform of μPAD for the sensitive detection of miRNAs.
Collapse
Affiliation(s)
- Xuemei Yin
- School of Chemistry and Chemical Engineering
- University of Jinan
- Jinan 250022
- P. R. China
| | - Linlin Liang
- School of Chemistry and Chemical Engineering
- University of Jinan
- Jinan 250022
- P. R. China
- Institute for Advanced Interdisciplinary Research
| | - Peini Zhao
- School of Chemistry and Chemical Engineering
- University of Jinan
- Jinan 250022
- P. R. China
| | - Feifei Lan
- School of Chemistry and Chemical Engineering
- University of Jinan
- Jinan 250022
- P. R. China
| | - Lina Zhang
- Shandong Provincial Key Laboratory of Preparation and Measurement of Building Materials
- University of Jinan
- Jinan 250022
- P. R. China
| | - Shenguang Ge
- Institute for Advanced Interdisciplinary Research
- University of Jinan
- Jinan 250022
- P. R. China
| | - Jinghua Yu
- School of Chemistry and Chemical Engineering
- University of Jinan
- Jinan 250022
- P. R. China
| |
Collapse
|