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Richard V, Lee K, Kerin MJ. MicroRNAs as Endocrine Modulators of Breast Cancer. Int J Mol Sci 2025; 26:3449. [PMID: 40244378 PMCID: PMC11989600 DOI: 10.3390/ijms26073449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 04/03/2025] [Accepted: 04/04/2025] [Indexed: 04/18/2025] Open
Abstract
Breast cancer is an aggressive disease of multiple subtypes with varying phenotypic, hormonal, and clinicopathological features, offering enhanced resistance to conventional therapeutic regimens. There is an unmet need for reliable molecular biomarkers capable of detecting the malignant transformation from the early stages of the disease to enhance diagnosis and treatment outcomes. A subset of small non-coding nucleic acid molecules, micro ribonucleic acids (microRNAs/miRNAs), have emerged as promising biomarkers due to their role in gene regulation and cancer pathogenesis. This review discusses, in detail, the different origins and hormone-like regulatory functionalities of miRNAs localized in tumor tissue and in the circulation, as well as their inherent stability and turnover that determines the utility of miRNAs as biomarkers for disease detection, monitoring, prognosis, and therapeutic targets.
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Affiliation(s)
- Vinitha Richard
- Discipline of Surgery, Lambe Institute for Translational Research, University of Galway, H91 V4AY Galway, Ireland
| | - Kevin Lee
- School of Medicine, University of Galway, H91 V4AY Galway, Ireland;
| | - Michael Joseph Kerin
- Discipline of Surgery, Lambe Institute for Translational Research, University of Galway, H91 V4AY Galway, Ireland
- School of Medicine, University of Galway, H91 V4AY Galway, Ireland;
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2
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Karaca Dogan B, Salman Yilmaz S, Izgi GN, Ozen M. Circulating non-coding RNAs as a tool for liquid biopsy in solid tumors. Epigenomics 2025; 17:335-358. [PMID: 40040488 PMCID: PMC11970797 DOI: 10.1080/17501911.2025.2467021] [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: 08/16/2024] [Accepted: 02/10/2025] [Indexed: 03/06/2025] Open
Abstract
Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.
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Affiliation(s)
- Beyza Karaca Dogan
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Seda Salman Yilmaz
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Medical Services and Techniques Medical Monitoring Techniques Pr. Vocational School of Health Services, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Gizem Nur Izgi
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
| | - Mustafa Ozen
- Department of Medical Genetics, Cerrahpaşa Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkiye
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
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3
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Huang Y, Zhou J, Deng Y, Li G, He S, Li H, Liu L. MiR-363: A potential biomarker of kidney diseases. Clin Chim Acta 2025; 567:120049. [PMID: 39631492 DOI: 10.1016/j.cca.2024.120049] [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: 03/24/2024] [Revised: 11/12/2024] [Accepted: 11/12/2024] [Indexed: 12/07/2024]
Abstract
MicroRNAs (miRNAs), a class of endogenous small RNAs with lengths of approximately 19-24 nucleotides, play important regulatory roles in cells. In recent years, miR-363 has emerged as a prominent member of the miR-92a family, participating in various biological functions, including cellular proliferation, cycle, migration, and apoptosis. In particular, miR-363 plays a critical role in acute kidney injury, renal fibrosis, and diabetic nephropathy and can serve as a biomarker for the diagnosis of renal cell carcinoma. Ongoing research is exploring its potential as a biomarker of other kidney diseases. This review focuses on the role of miR-363 in kidney diseases, elucidating its regulatory mechanisms and exploring its possible value as a biomarker of kidney diseases.
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Affiliation(s)
- Yiqi Huang
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China; School of Public Health, Guangzhou Medical University, Guangzhou 511436, China
| | - Jiazhen Zhou
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China
| | - Yaotang Deng
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China
| | - Guoliang Li
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China
| | - Shuirong He
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China; School of Public Health, Sun Yat-sen University, Guangzhou 510275, China
| | - Hecheng Li
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China; School of Public Health, Southern Medical University, Guangzhou 510145, China
| | - Lili Liu
- Institute of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510310, China.
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4
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Nafari NB, Zamani M, Mosayyebi B. Recent advances in lateral flow assays for MicroRNA detection. Clin Chim Acta 2025; 567:120096. [PMID: 39681230 DOI: 10.1016/j.cca.2024.120096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/13/2024] [Accepted: 12/13/2024] [Indexed: 12/18/2024]
Abstract
Lateral flow assays (LFAs) have emerged as pivotal tools for the rapid and reliable detection of microRNAs (miRNAs). It is believed that these biomarkers are crucial for the diagnosis and prognosis of various diseases, particularly cancer. Traditional miRNA detection techniques, such as quantitative PCR, are highly sensitive but have limited efficacy due to their complexity, high cost, and technical requirements. LFAs are valuable due to their simplicity, affordability, and portability, making them ideal for point-of-care testing in low-resource environments. However, challenges remain in developing highly sensitive and accurate LFA devices for miRNA detection. This review explores recent advancements in LFAs to improve miRNA detection sensitivity and specificity. Key innovations include signal amplification using isothermal methods, the application of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas systems for direct targeting of miRNAs, and the incorporation of nanomaterials, such as gold nanoparticles and nanorods, to enhance signal intensity. Using artificial intelligence (AI) algorithms enables precise, automated, and rapid quantification of miRNAs. Moreover, this review examines the ability of LFA-based devices to detect multiple miRNAs simultaneously. One of the most significant advancements is the detection of miR-21 levels as low as 20 pM and let-7a levels as low as 40 pM within ten minutes. This highlights the potential of these devices for clinical diagnostics.
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Affiliation(s)
- Nasim Barzegar Nafari
- Department of Pharmaceutical Science, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran
| | - Majid Zamani
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bashir Mosayyebi
- Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tehran University of Medical Sciences, Tehran, Iran.
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5
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Li X, Wang H, Qi X, Ji Y, Li F, Chen X, Li K, Li L. PCR Independent Strategy-Based Biosensors for RNA Detection. BIOSENSORS 2024; 14:200. [PMID: 38667193 PMCID: PMC11048163 DOI: 10.3390/bios14040200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 04/11/2024] [Accepted: 04/15/2024] [Indexed: 04/28/2024]
Abstract
RNA is an important information and functional molecule. It can respond to the regulation of life processes and is also a key molecule in gene expression and regulation. Therefore, RNA detection technology has been widely used in many fields, especially in disease diagnosis, medical research, genetic engineering and other fields. However, the current RT-qPCR for RNA detection is complex, costly and requires the support of professional technicians, resulting in it not having great potential for rapid application in the field. PCR-free techniques are the most attractive alternative. They are a low-cost, simple operation method and do not require the support of large instruments, providing a new concept for the development of new RNA detection methods. This article reviews current PCR-free methods, overviews reported RNA biosensors based on electrochemistry, SPR, microfluidics, nanomaterials and CRISPR, and discusses their challenges and future research prospects in RNA detection.
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Affiliation(s)
- Xinran Li
- Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (X.L.); (X.Q.); (F.L.)
| | - Haoqian Wang
- Development Center of Science and Technology, Ministry of Agriculture and Rural Affairs, Beijing 100176, China;
| | - Xin Qi
- Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (X.L.); (X.Q.); (F.L.)
| | - Yi Ji
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China;
| | - Fukai Li
- Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (X.L.); (X.Q.); (F.L.)
| | - Xiaoyun Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China;
| | - Kai Li
- Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (X.L.); (X.Q.); (F.L.)
| | - Liang Li
- Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China; (X.L.); (X.Q.); (F.L.)
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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.
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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
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Ullah H, Tian Y, Arbab S, Li K, Khan MIU, Rahman SU, Qadeer A, Muhammad N, Suleman, Hassan IU. Circulatory microRNAs in helminthiases: Potent as diagnostics biomarker, its potential role and limitations. Front Vet Sci 2022; 9:1018872. [PMID: 36387413 PMCID: PMC9650547 DOI: 10.3389/fvets.2022.1018872] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/30/2022] [Indexed: 08/08/2023] Open
Abstract
Infections caused by helminths are responsible for severe public health problems and economic burden on continental scale. Well-timed and precise diagnosis of helminth infections is critical for taking by appropriate approaches for pathogen control. Circulating miRNAs are stable diagnostic tool for different diseases found in a variety of body fluid. As diagnostic biomarkers in infectious diseases, miRNAs detection in body fluids of helminth infected hosts is growing promptly. Uncovering miRNAs is a relatively new tool, used for early-stage detection of helminth infection from experimental or non-invasive clinical samples. miRNAs can be detected in body fluids such as serum, saliva, urine, and tissues of helminth infected host, mainly blood offering important benefits for diagnosis accurately. In this review, we discuss different characteristics of helminth parasite-derived circulating and EV miRNAs, supporting its potential uses in for helminth diagnosis and treatment efficiency.
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Affiliation(s)
- Hanif Ullah
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Yali Tian
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Safia Arbab
- Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Ka Li
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Muhammad Inayat Ullah Khan
- State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences, Wuhan, China
| | - Sajid Ur Rahman
- Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
- Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Abdul Qadeer
- Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China
| | - Nehaz Muhammad
- Department of Zoology, University of Swabi, Swabi, Pakistan
| | - Suleman
- Department of Zoology, University of Swabi, Swabi, Pakistan
| | - Inam Ul Hassan
- Department of Microbiology, Hazara University Manshera, Manshera, Pakistan
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8
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Nguyen THN, Nguyen TTN, Nguyen TTM, Nguyen LHM, Huynh LH, Phan HN, Nguyen HT. Panels of circulating microRNAs as potential diagnostic biomarkers for breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 2022; 196:1-15. [DOI: 10.1007/s10549-022-06728-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/26/2022] [Indexed: 11/02/2022]
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9
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Weng S, Lin D, Lai S, Tao H, Chen T, Peng M, Qiu S, Feng S. Highly sensitive and reliable detection of microRNA for clinically disease surveillance using SERS biosensor integrated with catalytic hairpin assembly amplification technology. Biosens Bioelectron 2022; 208:114236. [DOI: 10.1016/j.bios.2022.114236] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 03/22/2022] [Accepted: 03/29/2022] [Indexed: 12/13/2022]
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Mohamed AA, Allam AE, Aref AM, Mahmoud MO, Eldesoky NA, Fawazy N, Sakr Y, Sobeih ME, Albogami S, Fayad E, Althobaiti F, Jafri I, Alsharif G, El-Sayed M, Abdelgeliel AS, Abdel Aziz RS. Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer. Diagnostics (Basel) 2022; 12:diagnostics12040789. [PMID: 35453838 PMCID: PMC9026478 DOI: 10.3390/diagnostics12040789] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/16/2022] [Accepted: 03/19/2022] [Indexed: 02/05/2023] Open
Abstract
Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2−negative (p < 0.001), estrogen receptor−positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.
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Affiliation(s)
- Amal Ahmed Mohamed
- Department of Biochemistry and Molecular Biology, National Hepatology and Tropical Medicine Research Institute, Cairo 11511, Egypt;
| | - Ahmed E. Allam
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
- Correspondence: (A.E.A.); (M.E.-S.)
| | - Ahmed M. Aref
- Faculty of Biotechnology, Modern Sciences and Arts University (MSA), Cairo 11511, Egypt;
| | - Maha Osama Mahmoud
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo 11511, Egypt;
| | - Noha A. Eldesoky
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo 11511, Egypt;
| | - Naglaa Fawazy
- Department of Clinical Pathology, National Institute of Diabetes & Endocrinology, Cairo 11511, Egypt; (N.F.); (Y.S.)
| | - Yasser Sakr
- Department of Clinical Pathology, National Institute of Diabetes & Endocrinology, Cairo 11511, Egypt; (N.F.); (Y.S.)
| | | | - Sarah Albogami
- Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; (S.A.); (E.F.); (F.A.); (I.J.)
| | - Eman Fayad
- Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; (S.A.); (E.F.); (F.A.); (I.J.)
| | - Fayez Althobaiti
- Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; (S.A.); (E.F.); (F.A.); (I.J.)
| | - Ibrahim Jafri
- Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; (S.A.); (E.F.); (F.A.); (I.J.)
| | - Ghadi Alsharif
- College of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia;
| | - Marwa El-Sayed
- Department of Microbiology and Immunology, Faculty of Medicine, South Valley University, Qena 83523, Egypt
- Correspondence: (A.E.A.); (M.E.-S.)
| | - Asmaa Sayed Abdelgeliel
- Department of Botany & Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt;
| | - Rania S. Abdel Aziz
- Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo 11976, Egypt;
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11
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Ferrier DC, Honeychurch KC. Carbon Nanotube (CNT)-Based Biosensors. BIOSENSORS 2021; 11:bios11120486. [PMID: 34940243 PMCID: PMC8699144 DOI: 10.3390/bios11120486] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 11/24/2021] [Accepted: 11/26/2021] [Indexed: 05/28/2023]
Abstract
This review focuses on recent advances in the application of carbon nanotubes (CNTs) for the development of sensors and biosensors. The paper discusses various configurations of these devices, including their integration in analytical devices. Carbon nanotube-based sensors have been developed for a broad range of applications including electrochemical sensors for food safety, optical sensors for heavy metal detection, and field-effect devices for virus detection. However, as yet there are only a few examples of carbon nanotube-based sensors that have reached the marketplace. Challenges still hamper the real-world application of carbon nanotube-based sensors, primarily, the integration of carbon nanotube sensing elements into analytical devices and fabrication on an industrial scale.
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Affiliation(s)
- David C. Ferrier
- Institute of Bio-Sensing Technology, Frenchay Campus, University of the West of England, Bristol BS16 1QY, UK;
| | - Kevin C. Honeychurch
- Institute of Bio-Sensing Technology, Frenchay Campus, University of the West of England, Bristol BS16 1QY, UK;
- Centre for Research in Biosciences, Frenchay Campus, Department of Applied Sciences, University of the West of England, Bristol BS16 1QY, UK
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12
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Cavallari I, Ciccarese F, Sharova E, Urso L, Raimondi V, Silic-Benussi M, D’Agostino DM, Ciminale V. The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers. Cancers (Basel) 2021; 13:5874. [PMID: 34884985 PMCID: PMC8656820 DOI: 10.3390/cancers13235874] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/17/2021] [Accepted: 11/18/2021] [Indexed: 12/13/2022] Open
Abstract
The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.
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Affiliation(s)
- Ilaria Cavallari
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Francesco Ciccarese
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Evgeniya Sharova
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Loredana Urso
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padova, Italy
| | - Vittoria Raimondi
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Micol Silic-Benussi
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
| | - Donna M. D’Agostino
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
- Department of Biomedical Sciences, University of Padua, 35131 Padova, Italy
| | - Vincenzo Ciminale
- Veneto Institute of Oncology IOV–IRCCS, 35128 Padova, Italy; (I.C.); (F.C.); (E.S.); (L.U.); (V.R.); (M.S.-B.)
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35128 Padova, Italy
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13
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Thu HNN, Vy HTN, Thanh TNN, Giang DTN, Nhan TN, Hoang NP, Hue TN. miRNA-16 as an Internal Control in Breast Cancer Studies: A Systematic Review and Meta-Analysis. Mol Biol 2021. [DOI: 10.1134/s0026893321050137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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14
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Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended. Cancers (Basel) 2021; 13:cancers13164028. [PMID: 34439180 PMCID: PMC8391908 DOI: 10.3390/cancers13164028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/06/2021] [Accepted: 08/06/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. A retrospective cohort of plasma samples divided into training and testing sets and a prospective cohort of women with suspicious imaging findings who underwent tissue biopsy were investigated through a global microRNA profile by OpenArray. Seven signatures, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were identified and validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 of them were confirmed in the prospective cohort. Abstract In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.
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15
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Mansoori B, Najafi S, Mohammadi A, AsadollahSeraj H, Savadi P, Mansoori B, Nazari A, Mokhtarzadeh A, Roshani E, Duijf PH, Cho WCS, Baradaran B. The synergy between miR-486-5p and tamoxifen causes profound cell death of tamoxifen-resistant breast cancer cells. Biomed Pharmacother 2021; 141:111925. [PMID: 34323695 DOI: 10.1016/j.biopha.2021.111925] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 06/08/2021] [Accepted: 07/12/2021] [Indexed: 11/24/2022] Open
Abstract
Breast cancer (BC) is the most common type of malignancy in women. A subset of breast cancers show resistance to endocrine-based therapies. The estrogen receptor (ER) plays a critical role in developing hormone-dependent BC. Loss of ER contributes to resistance to tamoxifen therapy and may contribute to mortality. Thus, it is crucial to overcome this problem. Here, using luciferase reporter assays, qRT-PCR, and Western blot analyses, we demonstrate that the microRNA miR-486-5p targets HMGA1 mRNA, decreasing its mRNA and protein levels in ER-positive (ER+) BC cells. Consistently, miR-486-5p is significantly downregulated, whereas HMGA1 is considerably upregulated in ER+ BC samples. Remarkably, while both miR-486-5p and tamoxifen individually cause G2/M cell cycle arrest, combination treatment synergistically causes profound cell death, specifically in tamoxifen-resistant ER+ cells but not in tamoxifen-sensitive ER+ cells. Combined treatment with miR-486-5p and tamoxifen also additively reduces cell migration, invasion, colony formation, mammary spheroid formation and a CD24-CD44+ cell population, representing decreased cancer stemness. However, these phenomena are independent of the tamoxifen responsiveness of the ER+ BC cells. Thus, miR-486-5p and tamoxifen exhibit additive and synergistic tumor-suppressive effects, most importantly causing profound cell death specifically in tamoxifen-resistant BC cells. Therefore, our work suggests that combining miR-486-5p replacement therapy with tamoxifen treatment is a promising strategy to treat endocrine therapy-resistant BC.
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Affiliation(s)
- Behzad Mansoori
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Souzan Najafi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Mohammadi
- Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | | | - Pouria Savadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behnaz Mansoori
- Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Afsaneh Nazari
- Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elmira Roshani
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Pascal Hg Duijf
- Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia; Centre for Data Science, Queensland University of Technology, Brisbane, Australia; University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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16
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Non-coding RNAs and lipids mediate the function of extracellular vesicles in cancer cross-talk. Semin Cancer Biol 2021; 74:121-133. [PMID: 34033894 DOI: 10.1016/j.semcancer.2021.04.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 04/07/2021] [Accepted: 04/23/2021] [Indexed: 11/22/2022]
Abstract
Research on extracellular vesicles (EVs) has been expanded, especially in the field of cancer. The cargoes in EVs, especially those in small EVs such as exosomes include microRNAs (miRNAs), mRNA, proteins, and lipids, are assumed to work cooperatively in the tumor microenvironment. In 2007, it was reported that miRNAs were abundant among the non-coding RNAs present in exosomes. Since then, many studies have investigated the functions of miRNAs and have tried to apply these molecules to aid in the diagnosis of cancer. Accordingly, many reviews of non-coding RNAs in EVs have been published for miRNAs. This review focuses on relatively new cargoes, covering long noncoding (lnc) RNAs, circular RNAs, and repeat RNAs, among non-coding RNAs. These RNAs, regardless of EV or cell type, have newly emerged due to the innovation of sequencing technology. The poor conservation, low quantity, and technical difficulty in detecting these RNA types have made it difficult to elucidate their functions and expression patterns. We herein summarize a limited number of studies. Although lipids are major components of EVs, current research on EVs focuses on miRNA and protein biology, while the roles of lipids in exosomes have not drawn attention. However, several recent studies revealed that phospholipids, which are components of the EV membrane, play important roles in the intercommunication between cells and in the generation of lipid mediators. Here, we review the reported roles of these molecules, and describe their potential in cancer biology.
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17
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Al Sulaiman D, Shapiro SJ, Gomez-Marquez J, Doyle PS. High-Resolution Patterning of Hydrogel Sensing Motifs within Fibrous Substrates for Sensitive and Multiplexed Detection of Biomarkers. ACS Sens 2021; 6:203-211. [PMID: 33351603 DOI: 10.1021/acssensors.0c02121] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
There has been an increasing and urgent demand to develop nucleic acid bioassays which not only offer high analytical performance but which are also amenable with point-of-care testing. Hydrogels present a versatile class of materials with biocompatible antifouling properties and the ability to be engineered for a range of advanced sensing applications. Fibrous substrates like nitrocellulose offer low-cost and durable platforms to run complex bioassays while enabling portability and ease of handling. We demonstrate herein the ability to synergistically combine these two materials into a portable biosensing platform by leveraging projection lithography. We demonstrate the direct polymerization of hydrogel sensing motifs within a range of fibrous substrates with precise control over their shape, size, location, and functionality. Spatial encoding of the hydrogel motifs enables the multiplex detection of multiple biomarkers on the same test. As a proof-of-concept, we apply the platform to the detection of microRNA, an emerging class of circulating biomarkers with promising potential for early diagnosis and monitoring of cancer. The assay offers a large dynamic range (over three orders of magnitude), high sensitivity (limit of detection of 2.5 amol), as well as versatility and ease of handling. Finally, the bioassay is validated using real biological samples, namely, total RNA extracted from the sera of late-stage breast cancer patients, demonstrating its utility and compatibility with clinical biosensing applications.
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Affiliation(s)
- Dana Al Sulaiman
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Sarah J. Shapiro
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Jose Gomez-Marquez
- Little Devices Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
| | - Patrick S. Doyle
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
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18
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Aksan H, Kundaktepe BP, Sayili U, Velidedeoglu M, Simsek G, Koksal S, Gelisgen R, Yaylim I, Uzun H. Circulating miR-155, let-7c, miR-21, and PTEN levels in differential diagnosis and prognosis of idiopathic granulomatous mastitis and breast cancer. Biofactors 2020; 46:955-962. [PMID: 32941675 DOI: 10.1002/biof.1676] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 08/06/2020] [Indexed: 12/13/2022]
Abstract
This study investigates whether the circulating miR-155, let-7c, miR-21, and PTEN levels to be used in the differential diagnosis of patients with idiopathic granulomatous mastitis (IGM) and breast cancer (BC). Forty-five patients with BC, 50 patients with IGM, and 48 healthy volunteers were included in the study. Serum miR-21 expression was significantly higher in BC (fold change = 2.42) and IGM group (fold change = 1.33) compared to control (p < .001). Serum miR-155 and let-7c expression levels were significantly lower in both groups compared to the control group (p < .001). miR-21 expression in BC was significantly higher than IGM (fold change = 1.976; p < .001). PTEN levels in BC were significantly higher than IGM (p < .001) and significantly lower than the control group (p < .001); the IGM group was significantly lower than the control group (p < .001). In addition to radiological data, serum miR-21 and PTEN levels may be noninvasive biomarkers that can help differentiate IGM from BC. The results of the study will lead to future studies in the differential diagnosis of IGM and BC.
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Affiliation(s)
- Hulya Aksan
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
- Department of Medical Biochemistry, Faculty of Medicine, Haliç University, Istanbul, Turkey
| | - Berrin Papila Kundaktepe
- Department of General Surgery, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Ugurcan Sayili
- Department of Public Health, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Mehmet Velidedeoglu
- Department of General Surgery, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Gonul Simsek
- Department of Physiology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Selcuk Koksal
- Department of Public Health, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Remise Gelisgen
- Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
| | - Ilhan Yaylim
- Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Hafize Uzun
- Department of Medical Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, Turkey
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19
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Gupta I, Rizeq B, Vranic S, Moustafa AEA, Al Farsi H. Circulating miRNAs in HER2-Positive and Triple Negative Breast Cancers: Potential Biomarkers and Therapeutic Targets. Int J Mol Sci 2020; 21:E6750. [PMID: 32942528 PMCID: PMC7554858 DOI: 10.3390/ijms21186750] [Citation(s) in RCA: 7] [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: 07/27/2020] [Revised: 09/02/2020] [Accepted: 09/06/2020] [Indexed: 12/14/2022] Open
Abstract
Breast cancer is one of the most prevalent diseases among women worldwide and is highly associated with cancer-related mortality. Of the four major molecular subtypes, HER2-positive and triple-negative breast cancer (TNBC) comprise more than 30% of all breast cancers. While the HER2-positive subtype lacks estrogen and progesterone receptors and overexpresses HER2, the TNBC subtype lacks estrogen, progesterone and HER2 receptors. Although advances in molecular biology and genetics have substantially ameliorated breast cancer disease management, targeted therapies for the treatment of estrogen-receptor negative breast cancer patients are still restricted, particularly for TNBC. On the other hand, it has been demonstrated that microRNAs, miRNAs or small non-coding RNAs that regulate gene expression are involved in diverse biological processes, including carcinogenesis. Moreover, circulating miRNAs in serum/plasma are among the most promising diagnostic/therapeutic tools as they are stable and relatively easy to quantify. Various circulating miRNAs have been identified in several human cancers including specific breast cancer subtypes. This review aims to discuss the role of circulating miRNAs as potential diagnostic and prognostic biomarkers as well as therapeutic targets for estrogen-receptor negative breast cancers, HER2+ and triple negative.
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Affiliation(s)
- Ishita Gupta
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (I.G.); (B.R.); (S.V.)
- Biomedical Research Centre, Qatar University, Doha P.O. Box 2713, Qatar
| | - Balsam Rizeq
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (I.G.); (B.R.); (S.V.)
- Biomedical Research Centre, Qatar University, Doha P.O. Box 2713, Qatar
| | - Semir Vranic
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (I.G.); (B.R.); (S.V.)
| | - Ala-Eddin Al Moustafa
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (I.G.); (B.R.); (S.V.)
- Biomedical Research Centre, Qatar University, Doha P.O. Box 2713, Qatar
| | - Halema Al Farsi
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (I.G.); (B.R.); (S.V.)
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20
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Liquid biopsy for breast cancer using extracellular vesicles and cell-free microRNAs as biomarkers. Transl Res 2020; 223:40-60. [PMID: 32413499 DOI: 10.1016/j.trsl.2020.04.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 03/31/2020] [Accepted: 04/07/2020] [Indexed: 12/24/2022]
Abstract
Improvement of breast cancer (BC) patient's outcome is directly related to early detection. However, there is still a lack of reliable biomarkers for diagnosis, prognosis and, treatment follow up in BC, leading researchers to study the potential of liquid biopsy based on circulating microRNAs (c-miRNAs). These c-miRNAs can be cell-free or associated with extracellular vesicles (EVs), and have great advantages such as stability in biofluids, noninvasive accessibility compared to current techniques (core-biopsy and surgery), and expression associated with pathogenic conditions. Recently, a new promising field of EV-derived miRNAs (EV-miRNAs) as cancer biomarkers has emerged, receiving special attention due to their selective vesicle sorting which makes them accurate for disease detection. In this review, we discuss new findings about c-miRNA and their potential as biomarkers for BC diagnosis, prognosis, and therapy. Additionally, we address the impact of limitations associated with the standardization of analysis techniques and methods on the implementation of these biomarkers in the clinical setting.
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21
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Pasculli B, Barbano R, Fontana A, Biagini T, Di Viesti MP, Rendina M, Valori VM, Morritti M, Bravaccini S, Ravaioli S, Maiello E, Graziano P, Murgo R, Copetti M, Mazza T, Fazio VM, Esteller M, Parrella P. Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors. Front Oncol 2020; 10:1415. [PMID: 32903519 PMCID: PMC7435065 DOI: 10.3389/fonc.2020.01415] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 07/06/2020] [Indexed: 01/12/2023] Open
Abstract
miR-155-5p is a well-known oncogenic microRNA, showing frequent overexpression in human malignancies, including breast cancer. Here, we show that high miR-155-5p levels are associated with unfavorable prognostic factors in two independent breast cancer cohorts (CSS cohort, n = 283; and TCGA-BRCA dataset, n = 1,095). Consistently, miR-155-5p results as differentially expressed in the breast cancer subgroups identified by the surrogate molecular classification in the CSS cohort and the PAM50 classifier in TCGA-BRCA dataset, with the TNBC and HER2-amplified tumors carrying the highest levels. Since the analysis of TCGA-BC dataset also demonstrated a significant association between miR-155-5p levels and the presence of mutations in homologous recombination (HR) genes, we hypothesized that miR-155-5p might affect cell response to the PARP-1 inhibitor Olaparib. As expected, miR-155-5p ectopic overexpression followed by Olaparib administration resulted in a greater reduction of cell viability as compared to Olaparib administration alone, suggesting that miR-155-5p might induce a synthetic lethal effect in cancer cells when coupled with PARP-1-inhibition. Overall, our data point to a role of miR-155-5p in homologous recombination deficiency and suggest miR-155-5p might be useful in predicting response to PARP1 inhibitors in the clinical setting.
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Affiliation(s)
- Barbara Pasculli
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratorio di Oncologia, San Giovanni Rotondo, Italy
| | - Raffaela Barbano
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratorio di Oncologia, San Giovanni Rotondo, Italy
| | - Andrea Fontana
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Biostatistica, San Giovanni Rotondo, Italy
| | - Tommaso Biagini
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratory of Bioinformatics Unit, San Giovanni Rotondo, Italy
| | - Maria Pia Di Viesti
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratorio di Oncologia, San Giovanni Rotondo, Italy
| | - Michelina Rendina
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratorio di Oncologia, San Giovanni Rotondo, Italy
| | - Vanna Maria Valori
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Oncologia, San Giovanni Rotondo, Italy
| | - Maria Morritti
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Oncologia, San Giovanni Rotondo, Italy
| | - Sara Bravaccini
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Biosciences Laboratory, Meldola, Italy
| | - Sara Ravaioli
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Biosciences Laboratory, Meldola, Italy
| | - Evaristo Maiello
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Oncologia, San Giovanni Rotondo, Italy
| | - Paolo Graziano
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Anatomia Patologica, San Giovanni Rotondo, Italy
| | - Roberto Murgo
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Chirurgia Senologica, San Giovanni Rotondo, Italy
| | - Massimiliano Copetti
- Fondazione IRCCS Casa Sollievo Della Sofferenza, UO di Biostatistica, San Giovanni Rotondo, Italy
| | - Tommaso Mazza
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratory of Bioinformatics Unit, San Giovanni Rotondo, Italy
| | - Vito Michele Fazio
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratorio di Oncologia, San Giovanni Rotondo, Italy
| | - Manel Esteller
- Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain.,Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.,Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain.,Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
| | - Paola Parrella
- Fondazione IRCCS Casa Sollievo Della Sofferenza, Laboratorio di Oncologia, San Giovanni Rotondo, Italy
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22
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Sadat-Ebrahimi SR, Aslanabadi N. Role of MicroRNAs in Diagnosis, Prognosis, and Treatment of Acute Heart Failure: Ambassadors from Intracellular Zone. Galen Med J 2020; 9:e1818. [PMID: 34466598 PMCID: PMC8343948 DOI: 10.31661/gmj.v9i0.1818] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 01/24/2020] [Accepted: 02/06/2020] [Indexed: 12/12/2022] Open
Abstract
Acute heart failure (AHF) is one of the burdensome diseases affecting a considerable proportion of the population. Recently, it has been demonstrated that micro-ribonucleic acids (miRNAs) can exert diagnostic, prognostic, and therapeutic roles in a variety of conditions including AHF. These molecules play essential roles in HF-related pathophysiology, particularly, cardiac fibrosis, and hypertrophy. Some miRNAs namely miRNA-423-5p are reported to have both diagnostic and prognostic capabilities. However, some studies suggest that combination of biomarkers is a much better way to achieve the highest accuracy such as the combination of miRNAs and N-terminal pro b-type Natriuretic Peptide (NT pro-BNP). Therefore, this review discusses different views towards various roles of miRNAs in AHF.
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Affiliation(s)
- Seyyed-Reza Sadat-Ebrahimi
- Cardiovascular Research Center, Madani Heart Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Naser Aslanabadi
- Cardiovascular Research Center, Madani Heart Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Correspondence to: Naser Aslanabadi, Professor of Cardiology, Cardiovascular Research Center, Madani Heart Center, Tabriz University of Medical Sciences, Tabriz, Iran Telephone Number: +989143110844 Email Address:
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Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma. Sci Rep 2020; 10:9414. [PMID: 32523124 PMCID: PMC7287053 DOI: 10.1038/s41598-020-66120-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 05/13/2020] [Indexed: 12/24/2022] Open
Abstract
Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.
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24
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Emergence of Circulating MicroRNAs in Breast Cancer as Diagnostic and Therapeutic Efficacy Biomarkers. Mol Diagn Ther 2020; 24:153-173. [DOI: 10.1007/s40291-020-00447-w] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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25
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Nassar FJ, Chamandi G, Tfaily MA, Zgheib NK, Nasr R. Peripheral Blood-Based Biopsy for Breast Cancer Risk Prediction and Early Detection. Front Med (Lausanne) 2020; 7:28. [PMID: 32118013 PMCID: PMC7026666 DOI: 10.3389/fmed.2020.00028] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Accepted: 01/20/2020] [Indexed: 12/17/2022] Open
Abstract
Among women, breast cancer (BC) is not only the most common cancer worldwide but also the leading cause of cancer death. Only 5–10% of breast cancer cases are attributed to inherited mutations (BRCA1, BRCA2, and other breast cancer susceptibility genes). Breast cancer incidence has been rising particularly in young women who are not eligible for mammography, and it has been acting as a burden especially in developing countries that lack screening and awareness programs. For this reason, research has shifted to use minimally invasive liquid biopsies especially blood-based biomarkers with potential value for breast cancer risk prediction and early detection. This mini-review will tackle the different blood-based biomarkers focusing mainly on circulating miRNA, circulating proteins, cell-free nucleic acids, methylation patterns, and exosomes. It also introduces the potential opportunities for the clinical use of these blood-based biomarkers for breast cancer risk prediction.
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Affiliation(s)
- Farah J Nassar
- Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ghada Chamandi
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Mohamad Ali Tfaily
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Nathalie Khoueiry Zgheib
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Rihab Nasr
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
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26
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Biocatalytic Amplification of UV Signal in Capillary Electrophoresis of MicroRNA. Int J Mol Sci 2019; 21:ijms21010051. [PMID: 31861744 PMCID: PMC6981575 DOI: 10.3390/ijms21010051] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 12/10/2019] [Accepted: 12/17/2019] [Indexed: 12/17/2022] Open
Abstract
MicroRNAs (miRNAs) are new potential biomarkers for early diagnosis and classification of cancer. This study is the first attempt to use biocatalytic amplification reactions combined with capillary electrophoresis to detect multiple miRNAs simultaneously. In this way, miRNAs, as catalysts, can catalyze two single strands of DNA to form double-strand DNA. Feasibility was demonstrated by non-gel capillary electrophoresis coupled with UV detection (NGCE-UV). The detection limit was improved down to 1.0 nM, having ca. 103-fold improvement. This method has a good linear range of between 3.0 nM and 300 nM, with R2 at 0.99, recovery at 88–115%, and peak area precision at 1–12.7%. Using three target miRNAs as a model can achieve the baseline separation and good selectivity. The proposed biocatalysis coupled with a capillary electrophoresis-based method is simple, rapid, multiplexed, and cost-effective, making it potentially applicable for simultaneous, large-scale screening for other nucleic acids biomarkers and related research.
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27
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Rangel ML, Heredia NI, Reininger B, McNeill L, Fernandez ME. Educating Hispanics About Clinical Trials and Biobanking. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2019; 34:1112-1119. [PMID: 30112612 PMCID: PMC6377344 DOI: 10.1007/s13187-018-1417-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Hispanics are under-represented in clinical research. To ensure that the Hispanic population benefits from advances in public health and medicine, including personalized medicine, there is a need to increase their participation in clinical trials and biobanking. There is a great need for improving awareness and addressing concerns individuals may have about participation. The purpose of this study was to adapt, implement, and evaluate educational materials about clinical trials and biobanking for Hispanic individuals. We adapted existing materials based on focus group data. We then trained four promotoras de salud to deliver education to Hispanic adults in community settings in Houston, TX. The promotoras educated 101 Hispanic adults, 51 on biobanking and 50 on clinical trials. Study staff administered brief pre- and post-test questionnaires that measured benefits, barriers, norms, self-efficacy, and intention to participate in either clinical trials or biobanking. Our sample was predominately female (83%) and Spanish-speaking (69%) and made less than $25,000 a year (87%). This intervention increased perceived benefits of participating in biobanking and clinical trials, self-efficacy for donating biospecimens, and intention to participate in biobanking if invited. Perceived barriers to participating declined. This study demonstrated that brief education can result in improved perceptions and attitudes related to participation in biobanking and clinical trials, and could increase participation. Researchers and practitioners could use these educational materials to educate Hispanic community members on clinical research potentially increasing participation rates in the future.
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Affiliation(s)
- M Lizette Rangel
- Department of Behavioral Science, MD Anderson Cancer Center, Houston, TX, USA.
| | - Natalia I Heredia
- Department of Health Promotion and Behavioral Sciences, UTHealth School of Public Health, Houston, TX, USA
- Center for Health Promotion and Prevention Research, UTHealth School of Public Health, Houston, TX, USA
| | - Belinda Reininger
- Department of Health Promotion and Behavioral Sciences, UTHealth School of Public Health, Brownsville Regional Campus, Brownsville, TX, USA
| | - Lorna McNeill
- Department of Health Disparities, MD Anderson Cancer Center, Houston, TX, USA
| | - Maria E Fernandez
- Department of Health Promotion and Behavioral Sciences, UTHealth School of Public Health, Houston, TX, USA
- Center for Health Promotion and Prevention Research, UTHealth School of Public Health, Houston, TX, USA
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28
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Abolghasemi M, Tehrani SS, Yousefi T, Karimian A, Mahmoodpoor A, Ghamari A, Jadidi-Niaragh F, Yousefi M, Kafil HS, Bastami M, Edalati M, Eyvazi S, Naghizadeh M, Targhazeh N, Yousefi B, Safa A, Majidinia M, Rameshknia V. MicroRNAs in breast cancer: Roles, functions, and mechanism of actions. J Cell Physiol 2019; 235:5008-5029. [PMID: 31724738 DOI: 10.1002/jcp.29396] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Accepted: 09/30/2019] [Indexed: 12/13/2022]
Abstract
Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.
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Affiliation(s)
- Maryam Abolghasemi
- Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Iran.,Student Research Committee, Babol University of medical sciences, Babol, Iran
| | - Sadra Samavarchi Tehrani
- Departmant of Clinical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.,Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Tooba Yousefi
- Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Iran.,Student Research Committee, Babol University of medical sciences, Babol, Iran
| | - Ansar Karimian
- Cellular and Molecular Biology Research Center, Babol University of Medical Sciences, Iran.,Student Research Committee, Babol University of medical sciences, Babol, Iran
| | - Ata Mahmoodpoor
- Anesthesiology Research Team, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aliakbar Ghamari
- Anesthesiology Research Team, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mehdi Yousefi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Milad Bastami
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdi Edalati
- Department of Laboratory Sciences, Paramedical Faculty, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shirin Eyvazi
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Naghizadeh
- Departmant of Clinical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.,Student Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloufar Targhazeh
- Student Research Committee, Babol University Of Medical Sciences, Babol, Iran
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Safa
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam
| | - Maryam Majidinia
- Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran
| | - Vahid Rameshknia
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Faculty of Medicine, Islamic Azad University, Tabriz, Iran
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29
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Shigemizu D, Akiyama S, Asanomi Y, Boroevich KA, Sharma A, Tsunoda T, Sakurai T, Ozaki K, Ochiya T, Niida S. A comparison of machine learning classifiers for dementia with Lewy bodies using miRNA expression data. BMC Med Genomics 2019; 12:150. [PMID: 31666070 PMCID: PMC6822471 DOI: 10.1186/s12920-019-0607-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 10/18/2019] [Indexed: 12/21/2022] Open
Abstract
Background Dementia with Lewy bodies (DLB) is the second most common subtype of neurodegenerative dementia in humans following Alzheimer’s disease (AD). Present clinical diagnosis of DLB has high specificity and low sensitivity and finding potential biomarkers of prodromal DLB is still challenging. MicroRNAs (miRNAs) have recently received a lot of attention as a source of novel biomarkers. Methods In this study, using serum miRNA expression of 478 Japanese individuals, we investigated potential miRNA biomarkers and constructed an optimal risk prediction model based on several machine learning methods: penalized regression, random forest, support vector machine, and gradient boosting decision tree. Results The final risk prediction model, constructed via a gradient boosting decision tree using 180 miRNAs and two clinical features, achieved an accuracy of 0.829 on an independent test set. We further predicted candidate target genes from the miRNAs. Gene set enrichment analysis of the miRNA target genes revealed 6 functional genes included in the DHA signaling pathway associated with DLB pathology. Two of them were further supported by gene-based association studies using a large number of single nucleotide polymorphism markers (BCL2L1: P = 0.012, PIK3R2: P = 0.021). Conclusions Our proposed prediction model provides an effective tool for DLB classification. Also, a gene-based association test of rare variants revealed that BCL2L1 and PIK3R2 were statistically significantly associated with DLB.
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Affiliation(s)
- Daichi Shigemizu
- Laboratory Chief, Division of Genomic Medicine, Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan. .,Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan. .,RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan. .,CREST, JST, Tokyo, 113-8510, Japan.
| | - Shintaro Akiyama
- Laboratory Chief, Division of Genomic Medicine, Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan
| | - Yuya Asanomi
- Laboratory Chief, Division of Genomic Medicine, Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan
| | - Keith A Boroevich
- RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
| | - Alok Sharma
- RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.,CREST, JST, Tokyo, 113-8510, Japan.,School of Engineering & Physics, University of the South Pacific, Suva, Fiji.,Institute for Integrated and Intelligent Systems, Griffith University, QLD, Brisbane, 4111, Australia
| | - Tatsuhiko Tsunoda
- Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan.,RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.,CREST, JST, Tokyo, 113-8510, Japan
| | - Takashi Sakurai
- The Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.,Department of Cognitive and Behavioral Science, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan
| | - Kouichi Ozaki
- Laboratory Chief, Division of Genomic Medicine, Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan.,RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, Fundamental Innovative Oncology Core Center, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.,Institute of Medical Science, Tokyo Medical University, Tokyo, 160-8402, Japan
| | - Shumpei Niida
- Laboratory Chief, Division of Genomic Medicine, Medical Genome Center, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi, 474-8511, Japan
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30
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Abstract
Deregulation of microRNA expression has been shown to play an important role in human malignancies. The identification of circulating-free miRNAs in biofluids a decade ago led to great enthusiasm and motivation to develop non-invasive tests based on the expression of these small non-coding RNAs. Herein, we review the progress within the field of research for identifying circulating miRNA cancer biomarkers and discuss the advantages and challenges associated with this. We also discuss the methodological and analytical variables, which may influence the final miRNA quantification and the importance of standardizing pre-analytical, analytical, and post-analytical processes in order to enable a successful translation of the results from basic research into the clinics.
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Affiliation(s)
- Gitte Brinch Andersen
- Department of Biomedicine, Aarhus University, The Bartholin Building, Bartholin Allé 6, 8000, Aarhus C, Denmark.,Laboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie Francois Jacob, Bâtiment G2, 2 rue Gaston Crémieux, 91000, Evry, France
| | - Jörg Tost
- Laboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie Francois Jacob, Bâtiment G2, 2 rue Gaston Crémieux, 91000, Evry, France.
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31
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Sato J, Shimomura A, Kawauchi J, Matsuzaki J, Yamamoto Y, Takizawa S, Sakamoto H, Ohno M, Narita Y, Ochiya T, Tamura K. Brain metastasis-related microRNAs in patients with advanced breast cancer. PLoS One 2019; 14:e0221538. [PMID: 31603918 PMCID: PMC6788729 DOI: 10.1371/journal.pone.0221538] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 08/08/2019] [Indexed: 12/25/2022] Open
Abstract
Brain metastasis is a major distant metastasis occurring in patients with advanced breast cancer, and is associated with poor prognosis. MicroRNAs (miRNAs) have a strong influence on various oncological functions and have been reported as potential biomarkers for detecting distant metastasis. Specific biomarkers and unique miRNAs for brain metastasis have yet to be reported. The aim of this study was to identify novel miRNAs in serum, to assist in the diagnosis of brain metastasis in patients with advanced breast cancer. We retrospectively analyzed the medical records of patients with breast cancer and collected clinical data. In addition, we evaluated serum miRNA profiles in patients with breast cancer, with and without brain metastasis, using high-sensitivity microarrays. All patients underwent computed tomography or magnetic resonance imaging brain imaging tests. A total of 51 serum samples from patients with breast cancer and brain metastasis, stored in the National Cancer Center Biobank, were used, and 28 serum samples were obtained from controls without brain metastasis. Two miRNAs, miR-4428 and miR-4480, could significantly distinguish patients with brain metastasis, with area under the receiver operating characteristic curve (AUC) values of 0.779 and 0.781, respectively, while a combination of miR-4428 and progesterone receptor had an AUC value of 0.884. No significant correlations were identified between the expression levels of these two miRNAs in serum and clinical data. We conclude that serum miR-4428 and miR-4480 may be useful as biomarkers for predicting brain metastasis in patients with breast cancer.
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Affiliation(s)
- Jun Sato
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Akihiko Shimomura
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Junpei Kawauchi
- Toray Industries, Inc., Kanagawa, Japan.,Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Yusuke Yamamoto
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Satoko Takizawa
- Toray Industries, Inc., Kanagawa, Japan.,Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Hiromi Sakamoto
- Department of Biobank and Tissue Resources, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan
| | - Makoto Ohno
- Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshitaka Narita
- Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.,Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan
| | - Kenji Tamura
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
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32
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Li M, Zou X, Xia T, Wang T, Liu P, Zhou X, Wang S, Zhu W. A five-miRNA panel in plasma was identified for breast cancer diagnosis. Cancer Med 2019; 8:7006-7017. [PMID: 31568692 PMCID: PMC6853814 DOI: 10.1002/cam4.2572] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 08/17/2019] [Accepted: 09/10/2019] [Indexed: 12/24/2022] Open
Abstract
Breast cancer (BC) is one of the most common cancers in females. Since early detection can bring prognosis benefit, discovery of novel noninvasive biomarkers for BC diagnosis is in urgent need. In this four‐phase study, we profiled miRNA expression in plasma samples from a total of 257 BC patients and 257 normal controls (NCs). Exiqon miRNA qPCR panel was used to select candidate miRNAs in the screening phase which were further analyzed using qRT‐PCR in the following training, testing and external validation phases. Finally, we identified five plasma miRNAs (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) whose expression levels were significantly different between BC patients and NCs. A 5‐miRNA panel in plasma with high sensitivity and specificity was then constructed to detect BC. The areas under the receiver‐operating characteristic curves (AUCs) of the panel were 0.683, 0.966, 0.978 for the training, testing and external validation sets, respectively. Expression of the identified miRNAs was further analyzed among 32 pairs of BC tissue and the adjacent normal tissue samples as well as plasma‐derived exosome samples from 32 BC patients vs 32 NCs. Let‐7b‐5p was contrarily down‐regulated in BC tissue. In exosomes samples, only miR‐122‐5p was significantly up‐regulated as in plasma for BC patients. In conclusion, we identified a 5‐miRNA plasma panel (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) that could serve as a promising biomarker for BC detection.
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Affiliation(s)
- Minghui Li
- Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Xuan Zou
- Fudan University Shanghai Cancer Center, Shanghai, PR China
| | - Tiansong Xia
- Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Tongshan Wang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Ping Liu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Xin Zhou
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Shui Wang
- Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China
| | - Wei Zhu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.,Department of Oncology and Radiotherapy, Nanjing Pukou Central Hospital, Nanjing, PR China
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33
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Zou X, Li M, Huang Z, Zhou X, Liu Q, Xia T, Zhu W. Circulating miR-532-502 cluster derived from chromosome X as biomarkers for diagnosis of breast cancer. Gene 2019; 722:144104. [PMID: 31493506 DOI: 10.1016/j.gene.2019.144104] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 08/17/2019] [Accepted: 09/02/2019] [Indexed: 12/31/2022]
Affiliation(s)
- Xuan Zou
- First Clinical College of Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, PR China
| | - Minghui Li
- Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China
| | - Zebo Huang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China; Department of Oncology, the Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi 214062, Jiangsu Province, PR China
| | - Xin Zhou
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China
| | - Qingxie Liu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China
| | - Tiansong Xia
- Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China.
| | - Wei Zhu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, PR China; Department of Oncology and Radiotherapy, Nanjing Pukou Central Hospital, 166 Shanghe Street, Pukou District, Nanjing 211800, PR China.
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34
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Shabaninejad Z, Yousefi F, Movahedpour A, Ghasemi Y, Dokanehiifard S, Rezaei S, Aryan R, Savardashtaki A, Mirzaei H. Electrochemical-based biosensors for microRNA detection: Nanotechnology comes into view. Anal Biochem 2019; 581:113349. [PMID: 31254490 DOI: 10.1016/j.ab.2019.113349] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 06/24/2019] [Accepted: 06/25/2019] [Indexed: 01/04/2023]
Abstract
Nanotechnology plays an undeniable significant role in medical sciences, particularly in the field of biomedicine. Development of several diagnostic procedures in medicine has been possible through the beneficial application of nano-materials, among which electrochemical nano-biosensors can be mentioned. They can be employed to quantify various clinical biomarkers in detection, evaluation, and follow up stages of the illnesses. MicroRNAs, a group of regulatory short RNA fragments, added a new dimension to the management and diagnosis of several diseases. Mature miRNAs are single-stranded RNA molecules approximately 22 nucleotides in length, which regulate a vast range of biological functions from cellular proliferation and death to cancer development and progression. Recently, diagnostic value of miRNAs in various diseases has been demonstrated. There are many traditional methods for detection of miRNAs including northern blotting, quantitative real time PCR (qRT-PCR), microarray technology, nanotechnology-based approaches, and molecular biology tools including miRNA biosensors. In comparison with other techniques, electrochemical nucleic acid biosensor methods exhibit many interesting features, and could play an important role in the future nucleic acid analysis. This review paper provides an overview of some different types of nanotechnology-based biosensors for detection of miRNAs.
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Affiliation(s)
- Zahra Shabaninejad
- Department of Nanobiotechnology, School of Basic Sciences, Tarbiat Modares University, Tehran, Iran
| | - Fatemeh Yousefi
- Department of Genetics, School of Basic Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ahmad Movahedpour
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Younes Ghasemi
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sadat Dokanehiifard
- Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Samaneh Rezaei
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reihaneh Aryan
- School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Savardashtaki
- Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
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35
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Clinical Translatability of "Identified" Circulating miRNAs for Diagnosing Breast Cancer: Overview and Update. Cancers (Basel) 2019; 11:cancers11070901. [PMID: 31252695 PMCID: PMC6678980 DOI: 10.3390/cancers11070901] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 06/12/2019] [Accepted: 06/24/2019] [Indexed: 12/24/2022] Open
Abstract
The effective management of patients with breast cancer (BC) depends on the early diagnosis of the disease. Currently, BC diagnosis is based on diagnostic imaging and biopsy, while the use of non-invasive circulating biomarkers for diagnosis remains an unmet need. Among the plethora of proposed non-invasive biomarkers, circulating microRNAs (miRNAs) have been considered promising diagnostic molecules because they are very stable in biological fluids and easily detectable. Although the discovery of miRNAs has opened a new avenue for their clinical application, the clinical translatability of these molecules remains unclear. This review analyses the role of circulating miRNAs as BC diagnostic biomarkers and focuses on two essential requirements to evaluate their clinical validity: i) Specificity and ii) consistent expression between the blood and tissue. These two issues were analyzed in depth using the Human miRNA Disease Database (HMDD v3.0) and the free search engine PubMed. One hundred and sixty three BC-associated miRNAs were selected and analyzed for their specificity among all human pathologies that shared deregulation (291) and consistent expression in the bloodstream and the tissue. In addition, we provide an overview of the current clinical trials examining miRNAs in BC. In conclusion, we highlight pitfalls in the translatability of circulating miRNAs into clinical practice due to the lack of specificity and a consistent expression pattern between the tissue and blood.
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36
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Circulating miR-29c, miR-30c, miR-193a-5p and miR-885-5p: Novel potential biomarkers for HTLV-1 infection diagnosis. INFECTION GENETICS AND EVOLUTION 2019; 74:103938. [PMID: 31242452 DOI: 10.1016/j.meegid.2019.103938] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/14/2019] [Accepted: 06/21/2019] [Indexed: 12/28/2022]
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is an oncoretrovirus that infects 5-10 million people worldwide. Currently, different methods are used to test HTLV-1 infection. However, a biomarker that could enable an early and accurate diagnosis of HTLV-1 infection is still lacking. Here, we compared the serum miRNA expression profile in HTLV-1 infected patients versus healthy individuals to identify a potential biomarker for diagnosis of HTLV-1 infection.TaqMan miRNA microarray (TLDA) was carried out to compare the miRNA expression profile in infected versus healthy individuals. Quantitative real-time RT-PCR (qRT-PCR) was applied to validate TLDA results. Receiver-operator characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of the most highly and significantly identified deregulated miRNA(s) as potential biomarker(s). We identified deregulated expression for ten miRNAs with miR-127, miR-136, miR-142-3p, miR-221, and miR-423-5p being down-regulated whilst let-7b, miR-29c, miR-30c, miR-193a-5p, and miR-885-5p being up-regulated in infected individuals. ROC curve analyses showed an AUC (Areas Under the ROC Curve) of 0.875 (95% CI: 0.7819-0.9581; P = .0021), 0.861 (95% CI: 0.7596-0.9754; P = .003), 0.856 (95% CI: 0.689-0.895; P = .011), and 0.849 (95% CI: 0.678-0.855; P = .017) for miR-29c, miR-30c, miR-193a-5p, and miR-885-5p respectively. Combined ROC analyses using these 4 miRNAs showed a greater AUC of 0.907 (95% CI: 0.809-1; P = .000001) indicating a robust diagnostic value of these 4 miRNAs. Our findings highlight serum miR-29c, miR-30c, miR-193a-5p and miR-885-5p as novel potential biomarkers important for HTLV-1 diagnosis.
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Why the Gold Standard Approach by Mammography Demands Extension by Multiomics? Application of Liquid Biopsy miRNA Profiles to Breast Cancer Disease Management. Int J Mol Sci 2019; 20:ijms20122878. [PMID: 31200461 PMCID: PMC6627787 DOI: 10.3390/ijms20122878] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2019] [Revised: 06/07/2019] [Accepted: 06/11/2019] [Indexed: 02/06/2023] Open
Abstract
In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the “golden standard” approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.
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38
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Gene Expression and miRNAs Profiling: Function and Regulation in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer. Cancers (Basel) 2019; 11:cancers11050646. [PMID: 31083383 PMCID: PMC6562440 DOI: 10.3390/cancers11050646] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 05/06/2019] [Accepted: 05/08/2019] [Indexed: 02/06/2023] Open
Abstract
Breast cancer is the second most common cause of cancer-related deaths among women worldwide. It is a heterogeneous disease with four major molecular subtypes. One of the subtypes, human epidermal growth factor receptor 2 (HER2)-enriched (HER2-positive) is characterized by the absence of estrogen and progesterone receptors and overexpression of HER2 receptor, and accounts for 15–20% of all breast cancers. Despite the anti-HER2 and cytotoxic chemotherapy, HER2 subtype is an aggressive disease with significant mortality. Recent advances in molecular biology techniques, including gene expression profiling, proteomics, and microRNA analysis, have been extensively used to explore the underlying mechanisms behind human breast carcinogenesis and metastasis including HER2-positive breast cancer, paving the way for developing new targeted therapies. This review focuses on recent advances on gene expression and miRNA status in HER2-positive breast cancer.
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39
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Shigemizu D, Akiyama S, Asanomi Y, Boroevich KA, Sharma A, Tsunoda T, Matsukuma K, Ichikawa M, Sudo H, Takizawa S, Sakurai T, Ozaki K, Ochiya T, Niida S. Risk prediction models for dementia constructed by supervised principal component analysis using miRNA expression data. Commun Biol 2019; 2:77. [PMID: 30820472 PMCID: PMC6389908 DOI: 10.1038/s42003-019-0324-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 01/24/2019] [Indexed: 02/07/2023] Open
Abstract
Alzheimer's disease (AD) is the most common subtype of dementia, followed by Vascular Dementia (VaD), and Dementia with Lewy Bodies (DLB). Recently, microRNAs (miRNAs) have received a lot of attention as the novel biomarkers for dementia. Here, using serum miRNA expression of 1,601 Japanese individuals, we investigated potential miRNA biomarkers and constructed risk prediction models, based on a supervised principal component analysis (PCA) logistic regression method, according to the subtype of dementia. The final risk prediction model achieved a high accuracy of 0.873 on a validation cohort in AD, when using 78 miRNAs: Accuracy = 0.836 with 86 miRNAs in VaD; Accuracy = 0.825 with 110 miRNAs in DLB. To our knowledge, this is the first report applying miRNA-based risk prediction models to a dementia prospective cohort. Our study demonstrates our models to be effective in prospective disease risk prediction, and with further improvement may contribute to practical clinical use in dementia.
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Affiliation(s)
- Daichi Shigemizu
- Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan. .,Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan. .,RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan. .,CREST, JST, Tokyo, 102-8666, Japan.
| | - Shintaro Akiyama
- Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan
| | - Yuya Asanomi
- Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan
| | - Keith A Boroevich
- RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
| | - Alok Sharma
- RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.,CREST, JST, Tokyo, 102-8666, Japan.,School of Engineering & Physics, University of the South Pacific, Suva, Fiji.,Institute for Integrated and Intelligent Systems, Griffith University, Brisbane, QLD, 4111, Australia
| | - Tatsuhiko Tsunoda
- Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan.,RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.,CREST, JST, Tokyo, 102-8666, Japan
| | - Kana Matsukuma
- Toray Industries, Inc., Kamakura, Kanagawa, 248-0036, Japan
| | | | - Hiroko Sudo
- Toray Industries, Inc., Kamakura, Kanagawa, 248-0036, Japan
| | | | - Takashi Sakurai
- The Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.,Department of Cognitive and Behavioral Science, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan
| | - Kouichi Ozaki
- Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan.,RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, Fundamental Innovative Oncology Core Center, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.,Institute of Medical Science, Tokyo Medical University, Tokyo, 160-8402, Japan
| | - Shumpei Niida
- Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi, 474-8511, Japan
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40
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Kontomanolis EN, Fasoulakis Z, Papamanolis V, Koliantzaki S, Dimopoulos G, Kambas NJ. The Impact of microRNAs in Breast Cancer Angiogenesis and Progression. Microrna 2019; 8:101-109. [PMID: 30332982 DOI: 10.2174/2211536607666181017122921] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 03/22/2018] [Accepted: 10/11/2018] [Indexed: 06/08/2023]
Abstract
OBJECTIVE The study aims to review the recent data considering the expression profile and the role of microRNAs in breast tumorigenesis, and their impact on -the vital for breast cancer progression- angiogenesis. METHODS PubMed was searched for studies focused on data that associate microRNA with breast cancer, using the terms ''breast", "mammary gland", "neoplasia'', "angiogenesis" and ''microRNA'' between 1997-2018. RESULTS Aberrant expression of several circulating and tissue miRNAs is observed in human breast neoplasms with the deregulation of several miRNAs having a major participation in breast cancer progression. Angiogenesis seems to be directly affected by either overexpression or down regulation of many miRNAs, defining the overall prognostic rates. Many miRNAs differentially expressed in breast cancer that reveal a key role in suppression - progression and metastasis of breast cancer along with the contribution of the EGF, TNF-a and EGF cytokines. Conclusion Angiogenesis has proven to be vital for tumor development and metastasis while microRNAs are proposed to have multiple biological roles, including participation in immunosuppressive, immunomodulatory and recent studies reveal their implication in angiogenesis and its possible use as prognostic factors in cancer Even though larger studies are needed in order to reach safe conclusions, important steps are made that reveal the connection of serum microRNA expression to the angiogenic course of breast cancer, while miRNAs could be potential prognostic factors for the different breast cancer types.
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Affiliation(s)
- Emmanuel N. Kontomanolis
- Department of Obstetrics & Gynecology, Democritus University in Alexandroupolis, Dragana, Greece
| | - Zacharias Fasoulakis
- Department of Obstetrics & Gynecology, Democritus University in Alexandroupolis, Dragana, Greece
| | | | - Sofia Koliantzaki
- Department of Obstetrics & Gynecology, General Hospital of Korinthos, Corinth, Greece
| | - Georgios Dimopoulos
- Department of Obstetrics & Gynecology, General Hospital of Korinthos, Corinth, Greece
| | - Nikolaos J. Kambas
- Department of Obstetrics & Gynecology, General Hospital of Korinthos, Corinth, Greece
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41
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Bhat SA, Majid S, Hassan T. MicroRNAs and its emerging role as breast cancer diagnostic marker- A review. ADVANCES IN BIOMARKER SCIENCES AND TECHNOLOGY 2019. [DOI: 10.1016/j.abst.2019.05.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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42
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Plasma miR-21, miR-155, miR-10b, and Let-7a as the potential biomarkers for the monitoring of breast cancer patients. Sci Rep 2018; 8:17981. [PMID: 30568292 PMCID: PMC6299272 DOI: 10.1038/s41598-018-36321-3] [Citation(s) in RCA: 102] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 11/19/2018] [Indexed: 12/19/2022] Open
Abstract
There is a pressing need for further studies to categorize and validate circulating microRNAs (miRs) in breast cancer patients that can be one of the novel strategies for cancer screening and monitoring. The present study is aimed to investigate the expression of the circulating candidate microRNAs after the operation, chemotherapy, and radiotherapy in the non-metastatic breast cancer patients. Tumor tissue and plasma samples were collected from the 30 patients with recently diagnosed Luminal A breast cancer. Control plasma samples were collected from the 10 healthy subjects. A panel of four miRs including miR-21, miR-55, miR-10b, and Let-7a were selected and their expression levels were measured before and after the operation, chemotherapy, and radiotherapy by using Real-Time PCR technique. The plasma expression of the miR-21, miR-155, and miR-10b was significantly increased and the Let-7a plasma expression decreased in the breast cancer patients compromised to the control ones. There was a similar expression pattern of the miRs between the tissue and plasma samples. The plasma levels of the miR-21, miR-155, and miR-10b were significantly down-regulated and the Let-7a plasma level was up-regulated after the operation, chemotherapy, and radiotherapy compromised to the pre-treatment. There was a significant difference in the miR-155 plasma level after the operation, chemotherapy, and radiotherapy compromised with each other. Moreover, there was no significant difference between the plasma levels of the miRs after the radiotherapy compromised to the control cases. The operation, chemotherapy, and radiotherapy led to a more reduction in the oncomiRs and an increase in the tumor suppressor-miRs. It seems that monitoring miRs during treatment might be considered as a respectable diagnostic tool for monitoring of breast cancer patients.
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43
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Lin CC, Law BF, Siegel PD, Hettick JM. Circulating miRs-183-5p, -206-3p and -381-3p may serve as novel biomarkers for 4,4'-methylene diphenyl diisocyanate exposure. Biomarkers 2018; 24:76-90. [PMID: 30074411 DOI: 10.1080/1354750x.2018.1508308] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Occupational exposure to the most widely used diisocyanate, 4,4'-methylene diphenyl diisocyanate (MDI), is a cause of occupational asthma (OA). Early recognition of MDI exposure and sensitization is essential for the prevention of MDI-OA. OBJECTIVE Identify circulating microRNAs (miRs) as novel biomarkers for early detection of MDI exposure and prevention of MDI-OA. MATERIALS AND METHODS Female BALB/c mice were exposed to one of three exposure regimens: dermal exposure to 1% MDI in acetone; nose-only exposure to 4580 ± 1497 μg/m3 MDI-aerosol for 60 minutes; or MDI dermal exposure/sensitization followed by MDI-aerosol inhalation challenge. Blood was collected and miRCURY™ miRs qPCR Profiling Service was used to profile circulate miRs from dermally exposed mice. Candidate miRs were identified and verified from mice exposed to three MDI-exposure regimens by TaqMan® miR assays. RESULTS Up/down-regulation patterns of circulating mmu-miRs-183-5p, -206-3p and -381-3p were identified and verified. Circulating mmu-miR-183-5p was upregulated whereas mmu-miRs-206-3p and -381-3p were downregulated in mice exposed via all three MDI exposure regimens. DISCUSSION AND CONCLUSION Upregulation of circulating miR-183-5p along with downregulation of circulating miRs-206-3p and -381-3p may serve as putative biomarkers of MDI exposure and may be considered as potential candidates for validation in exposed human worker populations.
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Affiliation(s)
- Chen-Chung Lin
- a Allergy and Clinical Immunology Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , WV , 26505 , USA
| | - Brandon F Law
- a Allergy and Clinical Immunology Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , WV , 26505 , USA
| | - Paul D Siegel
- a Allergy and Clinical Immunology Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , WV , 26505 , USA
| | - Justin M Hettick
- a Allergy and Clinical Immunology Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , WV , 26505 , USA
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44
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Circulating small non-coding RNAs associated with age, sex, smoking, body mass and physical activity. Sci Rep 2018; 8:17650. [PMID: 30518766 PMCID: PMC6281647 DOI: 10.1038/s41598-018-35974-4] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 11/13/2018] [Indexed: 12/15/2022] Open
Abstract
Small non-coding RNAs (sncRNA) are regulators of cell functions and circulating sncRNAs from the majority of RNA classes are potential non-invasive biomarkers. Understanding how common traits influence ncRNA expression is essential for assessing their biomarker potential. In this study, we identify associations between sncRNA expression and common traits (sex, age, self-reported smoking, body mass, self-reported physical activity). We used RNAseq data from 526 serum samples from the Janus Serum Bank and traits from health examination surveys. Ageing showed the strongest association with sncRNA expression, both in terms of statistical significance and number of RNAs, regardless of RNA class. piRNAs were abundant in the serum samples and they were associated to sex. Interestingly, smoking cessation generally restored RNA expression to non-smoking levels, although for some sncRNAs smoking-related expression levels persisted. Pathway analysis suggests that smoking-related sncRNAs target the cholinergic synapses and may therefore potentially play a role in smoking addiction. Our results show that common traits influence circulating sncRNA expression. It is clear that sncRNA biomarker analyses should be adjusted for age and sex. In addition, for specific sncRNAs, analyses should also be adjusted for body mass, smoking, physical activity and technical factors.
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45
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Shiino S, Matsuzaki J, Shimomura A, Kawauchi J, Takizawa S, Sakamoto H, Aoki Y, Yoshida M, Tamura K, Kato K, Kinoshita T, Kitagawa Y, Ochiya T. Serum miRNA-based Prediction of Axillary Lymph Node Metastasis in Breast Cancer. Clin Cancer Res 2018; 25:1817-1827. [PMID: 30482779 DOI: 10.1158/1078-0432.ccr-18-1414] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 09/07/2018] [Accepted: 11/20/2018] [Indexed: 11/16/2022]
Abstract
PURPOSE Sentinel lymph node biopsy (SLNB) is the gold-standard procedure for evaluating axillary lymph node (ALN) status in patients with breast cancer. However, the morbidity of SLNB is not negligible, and the procedure is invasive for patients without ALN metastasis. Here, we developed a diagnostic model for evaluating ALN status using a combination of serum miRNAs and clinicopathologic factors as a novel less-invasive biomarker.Experimental Design: Preoperative serum samples were collected from patients who underwent surgery for primary breast cancer or breast benign diseases between 2008 and 2014. A total of 958 serum samples (921 cases of primary breast cancer, including 630 cases in the no ALN metastasis group and 291 cases in the ALN metastasis group, and 37 patients with benign breast diseases) were analyzed by miRNA microarray. Samples were randomly divided into training and test sets. Logistic LASSO regression analysis was used to construct diagnostic models in the training set, which were validated in the test set. RESULTS An optimal diagnostic model was identified using a combination of two miRNAs (miR-629-3p and miR-4710) and three clinicopathologic factors (T stage, lymphovascular invasion, and ultrasound findings), which showed a sensitivity of 0.88 (0.84-0.92), a specificity of 0.69 (0.61-0.76), an accuracy of 0.818, and an area under the receiver operating characteristic curve of 0.86 in the test set. CONCLUSIONS Serum miRNA profiles may be useful for the diagnosis of ALN metastasis before surgery in a less-invasive manner than SLNB.
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Affiliation(s)
- Sho Shiino
- Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan.,Keio University School of Medicine, Tokyo, Japan
| | - Juntaro Matsuzaki
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Akihiko Shimomura
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | | | | | - Hiromi Sakamoto
- Department of Biobank and Tissue Resources, National Cancer Center Research Institute, Tokyo, Japan
| | | | - Masayuki Yoshida
- Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan
| | - Kenji Tamura
- Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Ken Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takayuki Kinoshita
- Department of Breast Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
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46
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Kashyap D, Tuli HS, Garg VK, Goel N, Bishayee A. Oncogenic and Tumor-Suppressive Roles of MicroRNAs with Special Reference to Apoptosis: Molecular Mechanisms and Therapeutic Potential. Mol Diagn Ther 2018; 22:179-201. [PMID: 29388067 DOI: 10.1007/s40291-018-0316-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
MicroRNAs (miRNAs) are the non-coding class of minute RNA molecules that negatively control post-transcriptional regulation of various functional genes. These miRNAs are transcribed from the loci present in the introns of functional or protein-coding genes, exons of non-coding genes, or even in the 3'-untranslated region (3'-UTR). They have potential to modulate the stability or translational efficiency of a variety of target RNA [messenger RNA (mRNA)]. The regulatory function of miRNAs has been elucidated in several pathological conditions, including neurological (Alzheimer's disease and Parkinson's disease) and cardiovascular conditions, along with cancer. Importantly, miRNA identification in cancer progression and invasion has evolved as an incipient era in cancer treatment. Several studies have shown the influence of miRNAs on various cancer processes, including apoptosis, invasion, metastasis and angiogenesis. In particular, apoptosis induction in tumor cells through miRNA has been extensively studied. The biphasic mode (up- and down-regulation) of miRNA expression in apoptosis and other cancer processes has already been determined. The findings of these studies could be utilized to develop potential therapeutic strategies for the management of various cancers. The present review critically describes the oncogenic and tumor suppressor role of miRNAs in apoptosis and other cancer processes, therapy resistance, and use of their presence in the body fluids as biomarkers.
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Affiliation(s)
- Dharambir Kashyap
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, Punjab, India
| | - Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar University, Mullana-Ambala, 133207, Haryana, India.
| | - Vivek Kumar Garg
- Department of Biochemistry, Government Medical College and Hospital, Chandigarh, 160030, Punjab, India
| | - Neelam Goel
- Department of Information Technology, University Institute of Engineering and Technology, Panjab University, Chandigarh, 160014, Punjab, India
| | - Anupam Bishayee
- Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, 33169, USA.
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47
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Shu L, Wang Z, Wang Q, Wang Y, Zhang X. Signature miRNAs in peripheral blood monocytes of patients with gastric or breast cancers. Open Biol 2018; 8:180051. [PMID: 30381359 PMCID: PMC6223219 DOI: 10.1098/rsob.180051] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 10/01/2018] [Indexed: 12/21/2022] Open
Abstract
The dysregulation of microRNAs (miRNAs), key posttranscriptional regulators of gene expression, is closely associated with cancer development. However, the miRNAs of monocytes, important cells of tumour immunity, have not been extensively explored. In the present study, the differentially expressed miRNAs of blood monocytes derived from gastric and breast cancer patients and healthy donors were characterized. The results indicated that 74 miRNAs were upregulated and 46 miRNAs were downregulated in monocytes of patients with breast or gastric cancers compared with the healthy donors, suggesting that these 120 miRNAs from transformed monocytes were associated with cancers. The differentially expressed miRNAs, 38 of which were novel, were further validated using quantitative real-time PCR. As an example, the results showed that miR-150-5p downregulated the CCR2 expression in monocytes by targeting Notch 3, thus leading to the suppression of tumorigenesis. The target gene analysis showed that 36 of the 120 miRNAs targeted cancer-related genes. KEGG pathway analysis indicated that the cancer-associated miRNAs were involved in pathways related to cancers, such as the HIF-1 signalling and the mTOR signalling pathways. Thus, our study provided new clues to comprehensively understand the relationship between miRNAs and cancers.
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Affiliation(s)
- Le Shu
- Laboratory for Marine Biology and Biotechnology of Qingdao National Laboratory for Marine Science and Technology and College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China
| | - Zhe Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People's Republic of China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233030, People's Republic of China
| | - Yumeng Wang
- Department of Gastroenterology, Chaohu Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Xiaobo Zhang
- Laboratory for Marine Biology and Biotechnology of Qingdao National Laboratory for Marine Science and Technology and College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China
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48
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Panoutsopoulou K, Avgeris M, Scorilas A. miRNA and long non-coding RNA: molecular function and clinical value in breast and ovarian cancers. Expert Rev Mol Diagn 2018; 18:963-979. [DOI: 10.1080/14737159.2018.1538794] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Affiliation(s)
- Konstantina Panoutsopoulou
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece
| | - Margaritis Avgeris
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece
| | - Andreas Scorilas
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece
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49
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Yoshioka Y, Katsuda T, Ochiya T. Extracellular vesicles and encapusulated miRNAs as emerging cancer biomarkers for novel liquid biopsy. Jpn J Clin Oncol 2018; 48:869-876. [DOI: 10.1093/jjco/hyy120] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 08/04/2018] [Indexed: 12/13/2022] Open
Affiliation(s)
- Yusuke Yoshioka
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Takeshi Katsuda
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
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50
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Lapshina AM, Khandaeva PM, Belaya ZE, Rozhinskaya LY, Melnichenko GA. [Role of microRNA in oncogenesis of pituitary tumors and their practical significance]. TERAPEVT ARKH 2018. [PMID: 28635944 DOI: 10.17116/terarkh2016888115-120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Microribonucleic acids (miRNAs) are a class of noncoding RNAs that regulate posttranscriptional gene expression. These molecules are regulators of cell proliferation, metabolism, apoptosis, and differentiation. MiRNAs are not degraded by RNAases and their concentrations can be measured in different body fluids, including serum. The expression of miRNAs varies in intact tissues and tumors, including pituitary adenomas. Pituitary tumors are encountered in 22.5% of the population and, in a number of cases, may be asymptomatic, but in case of invasion or/and hormone overproduction, their clinical presentation is severe with multiple symptoms leading to disability and even death. The mechanisms for the development and progression of pituitary tumors and the markers for remission and recurrence have not been adequately investigated. This literature review discusses the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.
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Affiliation(s)
- A M Lapshina
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - P M Khandaeva
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - Zh E Belaya
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - L Ya Rozhinskaya
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
| | - G A Melnichenko
- Endocrine Research Center, Ministry of Health of Russia, Moscow, Russia
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