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1
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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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2
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Ferreira T, Dias F, Alves Â, Gama A, Mano JF, Oliveira PA, Medeiros R. Let-7b, miR-29b, and miR-125b as Potential Biomarkers for Differentiating Canine Mammary Carcinoma Histological Types. Animals (Basel) 2024; 15:20. [PMID: 39794962 PMCID: PMC11718878 DOI: 10.3390/ani15010020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/19/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
Epigenetics is the study of changes in organisms that result from modifications in gene expression rather than alterations in the genetic code itself [...].
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Affiliation(s)
- Tiago Ferreira
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal;
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (F.D.); (Â.A.)
- Department of Chemistry, CICECO—Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;
| | - Francisca Dias
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (F.D.); (Â.A.)
| | - Ângela Alves
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (F.D.); (Â.A.)
- School of Medicine and Biomedical Sciences (ICBAS), University of Porto, 4050-513 Porto, Portugal
| | - Adelina Gama
- Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - João F. Mano
- Department of Chemistry, CICECO—Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;
| | - Paula A. Oliveira
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal;
- Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4Agro), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal; (F.D.); (Â.A.)
- Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal
- Research Department of the Portuguese League against Cancer—Regional Nucleus of the North (Liga Portuguesa Contra o Cancro—Núcleo Regional do Norte), 4200-177 Porto, Portugal
- Virology Service, Portuguese Institute of Oncology (IPO), 4200-072 Porto, Portugal
- Biomedical Research Center (CEBIMED), Faculty of Health Sciences of the Fernando Pessoa University, 4249-004 Porto, Portugal
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Piccinno E, Schirizzi A, Scalavino V, De Leonardis G, Donghia R, Fantasia A, Ricci AD, Lotesoriere C, Giannelli G, Serino G, D’Alessandro R. Circulating miR-23b-3p, miR-30e-3p, and miR-205-5p as Novel Predictive Biomarkers for Ramucirumab-Paclitaxel Therapy Outcomes in Advanced Gastric Cancer. Int J Mol Sci 2024; 25:13498. [PMID: 39769259 PMCID: PMC11677161 DOI: 10.3390/ijms252413498] [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: 11/29/2024] [Revised: 12/12/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025] Open
Abstract
Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37, p = 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.
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Affiliation(s)
- Emanuele Piccinno
- Laboratory of Molecular Medicine, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (E.P.); (V.S.)
| | - Annalisa Schirizzi
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (A.S.); (G.D.L.)
| | - Viviana Scalavino
- Laboratory of Molecular Medicine, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (E.P.); (V.S.)
| | - Giampiero De Leonardis
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (A.S.); (G.D.L.)
| | - Rossella Donghia
- Data Science Unit, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy;
| | - Alessia Fantasia
- Clinical Trial Unit, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy;
| | - Angela Dalia Ricci
- Medical Oncology Unit, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (A.D.R.); (C.L.)
| | - Claudio Lotesoriere
- Medical Oncology Unit, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (A.D.R.); (C.L.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy;
| | - Grazia Serino
- Laboratory of Molecular Medicine, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (E.P.); (V.S.)
| | - Rosalba D’Alessandro
- Laboratory of Experimental Oncology, National Institute of Gastroenterology, IRCCS “S. de Bellis” Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy; (A.S.); (G.D.L.)
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Suri C, Swarnkar S, Bhaskar LVKS, Verma HK. Non-Coding RNA as a Biomarker in Lung Cancer. Noncoding RNA 2024; 10:50. [PMID: 39452836 PMCID: PMC11514784 DOI: 10.3390/ncrna10050050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 09/20/2024] [Accepted: 09/24/2024] [Indexed: 10/26/2024] Open
Abstract
INTRODUCTION Lung cancer remains one of the most prevalent and deadly cancers globally, with high mortality rates largely due to late-stage diagnosis, aggressive progression, and frequent recurrence. Despite advancements in diagnostic techniques and therapeutic interventions, the overall prognosis for lung cancer patients continues to be dismal. METHOD Emerging research has identified non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, as critical regulators of gene expression, significantly influencing cancer biology. These ncRNAs play pivotal roles in various aspects of lung cancer pathogenesis, including tumor initiation, progression, metastasis, and resistance to therapy. RESULTS We provide a comprehensive analysis of the current understanding of ncRNAs in lung cancer, emphasizing their potential as biomarkers for early diagnosis, prognostication, and the prediction of the therapeutic response. We explore the biological functions of ncRNAs, their involvement in key oncogenic pathways, and the molecular mechanisms by which they modulate gene expression and cellular processes in lung cancer. Furthermore, this review highlights recent advances in ncRNA-based diagnostic tools and therapeutic strategies, such as miRNA mimics and inhibitors, lncRNA-targeted therapies, and circRNA-modulating approaches, offering promising avenues for personalized medicine. CONCLUSION Finally, we discuss the challenges and future directions in ncRNA research, including the need for large-scale validation studies and the development of efficient delivery systems for ncRNA-based therapies. This review underscores the potential of ncRNAs to revolutionize lung cancer management by providing novel diagnostic and therapeutic options that could improve patient outcomes.
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Affiliation(s)
- Chahat Suri
- Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada;
| | - Shashikant Swarnkar
- Department of Biochemistry, C.C.M. Medical College, Bhilai 490020, Chhattisgarh, India;
| | - LVKS Bhaskar
- Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, Chhattisgarh, India;
| | - Henu Kumar Verma
- Department of Immunopathology, Institute of lungs Health and Immunity, Comprehensive Pnemology Center, Helmholtz Zentrum, Neuherberg, 85764 Munich, Germany
- Lung Health and Immunity, Comprehensive Pneumology Center, Helmholtz Zentrum, Neuherberg, 85764 Munich, Germany
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Mihai AM, Ianculescu LM, Suciu N. MiRNAs as potential biomarkers in early breast cancer detection: a systematic review. J Med Life 2024; 17:549-554. [PMID: 39296436 PMCID: PMC11407494 DOI: 10.25122/jml-2024-0322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Accepted: 05/31/2024] [Indexed: 09/21/2024] Open
Abstract
Breast cancer remains a significant global health challenge, with high incidence and mortality rates. While mammography has contributed to declining mortality, its limitations in sensitivity and specificity for early detection, particularly in distinguishing between pure atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC), highlight the need for more precise tools. Even with core needle biopsy (CNB), conclusive diagnoses often require surgical excision. This underscores the urgency for non-invasive biomarkers to improve early detection and differentiation, potentially reducing invasive procedures. Recent research has shifted focus from mRNA to microRNAs (miRNAs) as promising biomarkers for breast cancer screening. These small non-coding RNAs, which exhibit abnormal expression patterns in breast cancer patients' tissue and serum/plasma, play crucial roles in early breast cancer development by modulating proto-oncogenes or tumor suppressor genes at the post-transcriptional level. Notably, miRNAs such as miR-21, miR-155, and miR-200c are key regulators of cell proliferation and apoptosis, with the potential to distinguish between normal tissue and various stages of breast lesions, including ADH, DCIS, and IDC. Additionally, miRNAs in serum and plasma offer a non-invasive method to differentiate breast cancer stages. This review aims to consolidate current knowledge on early breast lesions and explore the potential of miRNAs as biomarkers for early breast cancer detection, which could enhance risk prediction and reduce reliance on invasive diagnostic procedures.
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Affiliation(s)
- Ana-Maria Mihai
- Polizu Department, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
| | - Laura Maria Ianculescu
- Polizu Department, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
| | - Nicolae Suciu
- Polizu Department, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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6
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Heidarzadehpilehrood R, Pirhoushiaran M. Biomarker potential of competing endogenous RNA networks in Polycystic Ovary Syndrome (PCOS). Noncoding RNA Res 2024; 9:624-640. [PMID: 38571815 PMCID: PMC10988127 DOI: 10.1016/j.ncrna.2024.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/21/2023] [Accepted: 01/08/2024] [Indexed: 04/05/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common condition affecting women of reproductive age globally. PCOS continues to be the largest contributing factor to female infertility despite significant progress in our knowledge of the molecular underpinnings and treatment of the condition. The fact that PCOS is a very diverse condition makes it one of the key reasons why we haven't been able to overcome it. Non-coding RNAs (ncRNAs) are implicated in the development of PCOS, according to growing evidence. However, it is unclear how the complex regulatory relationships between the many ncRNA types contribute to the growth of this malignancy. Competing endogenous RNA (ceRNA), a recently identified mechanism in the RNA world, suggests regulatory interactions between various RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). Recent studies on PCOS have shown that dysregulation of multiple ceRNA networks (ceRNETs) between these ncRNAs plays crucial roles in developing the defining characteristics of PCOS development. And it is believed that such a finding may open a new door for a deeper comprehension of PCOS's unexplored facets. In addition, it may be able to provide fresh biomarkers and effective therapy targets for PCOS. This review will go over the body of information that exists about the primary roles of ceRNETs before highlighting the developing involvement of several newly found ceRNETs in a number of PCOS characteristics.
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Affiliation(s)
- Roozbeh Heidarzadehpilehrood
- Department of Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
| | - Maryam Pirhoushiaran
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417613151, Iran
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Mohan Lal P, Hamza Siddiqui M, Soulat A, Mohan A, Tanush D, Tirath K, Raja S, Khuzzaim Khan M, Raja A, Chaulagain A, Tejwaney U. MicroRNAs as promising biomarkers and potential therapeutic agents in breast cancer management: a comprehensive review. Ann Med Surg (Lond) 2024; 86:3543-3550. [PMID: 38846828 PMCID: PMC11152842 DOI: 10.1097/ms9.0000000000002075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 04/08/2024] [Indexed: 06/09/2024] Open
Abstract
Breast cancer (BC), a complex and varied ailment, poses a significant global health burden. MicroRNAs (miRNAs) have emerged as vital regulators in BC progression, with potential implications for diagnosis and treatment. This review aims to synthesize current insights into miRNA dysregulation in BC. MiRNAs, small RNA molecules, govern gene expression post-transcriptionally and are implicated in BC initiation, metastasis, and therapy resistance. Differential expression of specific miRNAs in BC tissues versus normal breast tissue sheds light on underlying molecular mechanisms. MiRNAs also offer promise as diagnostic biomarkers due to their stable nature, accessibility in bodily fluids, and altered expression patterns in early-stage disease, augmenting conventional diagnostic methods. Beyond diagnosis, miRNAs also hold promise as therapeutic targets in BC. By modulating the expression of specific dysregulated miRNAs, it may be possible to restore normal cellular functions and overcome treatment resistance. However, several challenges need to be addressed before miRNA-based therapies can be translated into clinical practice, including the development of efficient delivery systems and rigorous evaluation through preclinical and clinical trials. MiRNAs represent a promising avenue in BC research, offering potential applications in diagnosis, prognosis, and therapeutic interventions. As our understanding of miRNA biology deepens and technology advances, further research and collaborative efforts are needed to fully exploit the diagnostic and therapeutic potential of miRNAs in BC management. Ultimately, the integration of miRNA-based approaches into clinical practice may lead to more personalized and effective strategies for combating this devastating disease.
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Affiliation(s)
| | | | | | | | | | | | - Sandesh Raja
- Dow Medical College, Dow University of Health Sciences
| | | | - Adarsh Raja
- Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
| | - Aayush Chaulagain
- Shaheed Ziaur Rahman Medical College and Hospital, Bogra, Bangladesh
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8
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Saranya I, Dharshini VS, Akshaya RL, Subhashini PS, Selvamurugan N. Regulatory and therapeutic implications of competing endogenous RNA network in breast cancer progression and metastasis: A review. Int J Biol Macromol 2024; 266:131075. [PMID: 38531528 DOI: 10.1016/j.ijbiomac.2024.131075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/12/2024] [Accepted: 03/20/2024] [Indexed: 03/28/2024]
Abstract
Breast cancer (BC) is a global health concern, and development of diagnostic tools and targeted treatments for BC remains challenging. Therapeutic approaches for BC often involve a combination of surgery, radiation therapy, chemotherapy, targeted therapy, and hormone therapy. In recent years, there has been a growing interest in the role of noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs) and microRNAs (miRNAs), in BC and their therapeutic implications. Various biological processes such as cell proliferation, migration, and apoptosis rely on the activities of these ncRNAs, and their dysregulation has been implicated in BC progression. The regulatory function of the competitive endogenous RNA (ceRNA) network, which comprises lncRNAs, miRNAs, and mRNAs, has been the subject of extensive pathophysiological research. Most lncRNAs serve as molecular sponges for miRNAs and sequester their activities, thereby regulating the expression of target mRNAs and contributing to the promotion or inhibition of BC progression. This review summarizes recent findings on the role of ceRNA networks in BC progression, metastasis, and therapeutic resistance, and highlights the association of ceRNA networks with transcription factors and signaling pathways. Understanding the ceRNA network can lead to the discovery of biomarkers and targeted treatment methods to prevent the spread and metastasis of BC.
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Affiliation(s)
- I Saranya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - V Sowfika Dharshini
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - R L Akshaya
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - P Sakthi Subhashini
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India
| | - N Selvamurugan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
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Piergentili R, Marinelli E, Cucinella G, Lopez A, Napoletano G, Gullo G, Zaami S. miR-125 in Breast Cancer Etiopathogenesis: An Emerging Role as a Biomarker in Differential Diagnosis, Regenerative Medicine, and the Challenges of Personalized Medicine. Noncoding RNA 2024; 10:16. [PMID: 38525735 PMCID: PMC10961778 DOI: 10.3390/ncrna10020016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 02/10/2024] [Accepted: 02/19/2024] [Indexed: 03/26/2024] Open
Abstract
Breast Cancer (BC) is one of the most common cancer types worldwide, and it is characterized by a complex etiopathogenesis, resulting in an equally complex classification of subtypes. MicroRNA (miRNA or miR) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to tumor development and angiogenesis in different types of cancer. Recently, complex interactions among coding and non-coding RNA have been elucidated, further shedding light on the complexity of the roles these molecules fulfill in cancer formation. In this context, knowledge about the role of miR in BC has significantly improved, highlighting the deregulation of these molecules as additional factors influencing BC occurrence, development and classification. A considerable number of papers has been published over the past few years regarding the role of miR-125 in human pathology in general and in several types of cancer formation in particular. Interestingly, miR-125 family members have been recently linked to BC formation as well, and complex interactions (competing endogenous RNA networks, or ceRNET) between this molecule and target mRNA have been described. In this review, we summarize the state-of-the-art about research on this topic.
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Affiliation(s)
- Roberto Piergentili
- Institute of Molecular Biology and Pathology, Italian National Research Council (CNR-IBPM), 00185 Rome, Italy;
| | - Enrico Marinelli
- Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, 04100 Latina, Italy;
| | - Gaspare Cucinella
- Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy; (G.C.); (A.L.); (G.G.)
| | - Alessandra Lopez
- Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy; (G.C.); (A.L.); (G.G.)
| | - Gabriele Napoletano
- Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Section of Forensic Medicine, “Sapienza” University of Rome, 00161 Rome, Italy;
| | - Giuseppe Gullo
- Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy; (G.C.); (A.L.); (G.G.)
| | - Simona Zaami
- Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Section of Forensic Medicine, “Sapienza” University of Rome, 00161 Rome, Italy;
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Jones N, Nonaka T. Circulating miRNAs as biomarkers for the diagnosis in patients with melanoma: systematic review and meta-analysis. Front Genet 2024; 15:1339357. [PMID: 38419786 PMCID: PMC10899317 DOI: 10.3389/fgene.2024.1339357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 01/29/2024] [Indexed: 03/02/2024] Open
Abstract
Objective: Melanoma is the most aggressive and deadly form of skin cancer, especially at later stages. There is currently no excellent diagnostic test established for the diagnosis of melanoma; however, circulating microRNAs (miRNAs) have shown some promise. We seek to conduct a systematic review and meta-analysis to establish the clinical utility of circulating miRNAs in diagnosing melanoma. Methods: PubMed, Wiley, and Web of Science were searched for studies that determined miRNA sensitivity and specificity in patients with melanoma. The included studies were assessed in Stata, and the sensitivity, specificity, summary receiver operating characteristic (SROC), positive likelihood ratio, negative likelihood ratio, and the area under the SROC curve (AUC) were calculated. Results: 9 studies with 898 melanoma patients were included in the meta-analysis. The circulating miRNAs showed high diagnostic accuracy with a sensitivity of 0.89 (p < 0.001), specificity of 0.85 (p < 0.001), diagnostic odds ratio of 45, and an area under the curve of 0.93. Conclusion: Circulating miRNAs have shown a high diagnostic power in detecting melanoma.
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Affiliation(s)
- Nicholas Jones
- School of Medicine, Louisiana State University Health Shreveport, Shreveport, LA, United States
| | - Taichiro Nonaka
- Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, United States
- Feist-Weiller Cancer Center, Louisiana State University Health Shreveport, Shreveport, LA, United States
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Turkoglu F, Calisir A, Ozturk B. Clinical importance of serum miRNA levels in breast cancer patients. Discov Oncol 2024; 15:19. [PMID: 38280134 PMCID: PMC10821853 DOI: 10.1007/s12672-024-00871-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 01/21/2024] [Indexed: 01/29/2024] Open
Abstract
There is limited data on the relationship of miRNAs with parameters that may affect surgical management or reflect tumour prognosis. It was aimed to evaluate serum miRNA levels in breast carcinoma cases and reveal the relationship between these levels and prognosis-related factors such as the histological type of the tumour, estrogen receptor, progesterone receptor, Ki-67 index, HER-2neu, E-cadherin, tumour size, CK5/6, CA15.3 levels, number of tumour foci, number of metastatic lymph nodes, and status of receiving neoadjuvant therapy. Thirty-five patients with a histopathologically confirmed breast carcinoma diagnosis in the case group and 35 healthy individuals in the control group were examined. miR-206, miR-17-5p, miR-125a, miR-125b, miR-200a, Let-7a, miR-34a, miR-31, miR-21, miR-155, miR-10b, miR-373, miR-520c, miR-210, miR-145, miR-139-5p, miR-195, miR-99a, miR-497 and miR-205 expression levels in the serum of participants were determined using the Polymerase Chain Reaction method. While serum miR-125b and Let-7a expression levels were significantly higher in breast cancer patients, miR-17-5p, miR-125a, miR-200a, miR-34a, miR-21, miR-99a and miR-497 levels were significantly lower in them. The Let-7a expression level had a statistically significant relationship with breast cancer histological type and HER-2neu parameters, miR-17-5p, miR-125b, Let-7a, miR-34a, miR-21 and miR-99a levels with E-cadherin, miR-34a, miR-99a and miR-497 with CA15.3, miR-125b, miR-200a and miR-34a with the number of metastatic lymph nodes, miR-125a with the number of tumour foci and miR-200a with the status of having the neoadjuvant therapy. Serum miR-17-5p, miR-125a, miR-125b, miR-200a, Let-7a, miR-34a, miR-21, miR-99a and miR-497 expression levels were determined to have predictive and prognostic importance in breast cancer.
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Affiliation(s)
- Fatih Turkoglu
- Department of General Surgery, Faculty of Medicine, Selcuk University, Akademi Mahallesi Yeni İstanbul Caddesi No:313, Selçuk Üniversitesi Alaeddin Keykubat Yerleşkesi, Selçuklu, Konya, 42130, Turkey.
| | - Akin Calisir
- Department of General Surgery, Faculty of Medicine, Selcuk University, Akademi Mahallesi Yeni İstanbul Caddesi No:313, Selçuk Üniversitesi Alaeddin Keykubat Yerleşkesi, Selçuklu, Konya, 42130, Turkey
| | - Bahadir Ozturk
- Department of Biochemistry, Faculty of Medicine, Selcuk University, Konya, Turkey
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12
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Masroni MSB, Lee KW, Lee VKM, Ng SB, Law CT, Poon KS, Lee BTK, Liu Z, Tan YP, Chng WL, Tucker S, Ngo LSM, Yip GWC, Nga ME, Hue SSS, Putti TC, Bay BH, Lin Q, Zhou L, Hartman M, Loh TP, Lakshmanan M, Lee SY, Tergaonkar V, Chua H, Lee AVH, Yeo EYM, Li MH, Chang CF, Kee Z, Tan KML, Tan SY, Koay ESC, Archetti M, Leong SM. Dynamic altruistic cooperation within breast tumors. Mol Cancer 2023; 22:206. [PMID: 38093346 PMCID: PMC10720132 DOI: 10.1186/s12943-023-01896-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 11/05/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance. METHODS MicroRNA profiling was performed on circulating tumor cells collected from the blood of treated breast cancer patients. Cancer cell lines ectopically expressing candidate miRNA were used in co-culture experiments and treated with docetaxel. Ecological parameters like relative survival and relative fitness were assessed using flow cytometry. Functional studies and characterization performed in vitro and in vivo include proliferation, iTRAQ-mass spectrometry, RNA sequencing, inhibition by small molecules and antibodies, siRNA knockdown, CRISPR/dCas9 inhibition and fluorescence imaging of promoter reporter-expressing cells. Mathematical modeling based on evolutionary game theory was performed to simulate spatial organization of cancer cells. RESULTS Opposing cancer processes underlie altruism: an oncogenic process involving secretion of IGFBP2 and CCL28 by the altruists to induce survival benefits in neighboring cells under taxane exposure, and a self-sacrificial tumor suppressive process impeding proliferation of altruists via cell cycle arrest. Both processes are regulated concurrently in the altruists by miR-125b, via differential NF-κB signaling specifically through IKKβ. Altruistic cells persist in the tumor despite their self-sacrifice, as they can regenerate epigenetically from non-altruists via a KLF2/PCAF-mediated mechanism. The altruists maintain a sparse spatial organization by inhibiting surrounding cells from adopting the altruistic fate via a lateral inhibition mechanism involving a GAB1-PI3K-AKT-miR-125b signaling circuit. CONCLUSIONS Our data reveal molecular mechanisms underlying manifestation, persistence and spatial spread of cancer cell altruism. A minor population behave altruistically at a cost to itself producing a collective benefit for the tumor, suggesting tumors to be dynamic social systems governed by the same rules of cooperation in social organisms. Understanding cancer cell altruism may lead to more holistic models of tumor evolution and drug response, as well as therapeutic paradigms that account for social interactions. Cancer cells constitute tractable experimental models for fields beyond oncology, like evolutionary ecology and game theory.
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Affiliation(s)
- Muhammad Sufyan Bin Masroni
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Kee Wah Lee
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore
| | - Victor Kwan Min Lee
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
- NUS Centre for Cancer Research (N2CR), MD6, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore, 117599, Singapore
| | - Siok Bian Ng
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
- NUS Centre for Cancer Research (N2CR), MD6, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore, 117599, Singapore
| | - Chao Teng Law
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Kok Siong Poon
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Bernett Teck-Kwong Lee
- Centre for Biomedical Informatics, Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, NTU Main Campus, 59 Nanyang Drive, Level 4, Singapore, 636921, Singapore
| | - Zhehao Liu
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore
| | - Yuen Peng Tan
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Wee Ling Chng
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Steven Tucker
- Tucker Medical Pte Ltd, Novena Specialist Centre, 8 Sinaran Drive #04-03, Singapore, 307470, Singapore
| | - Lynette Su-Mien Ngo
- Raffles Cancer Centre, Raffles Hospital, 585 North Bridge Road, Singapore, 188770, Singapore
- Current address: Curie Oncology Pte Ltd, Mount Elizabeth Novena Specialist Centre, 38 Irrawaddy Road, Level 8, #08-29/30, Singapore, 329563, Singapore
| | - George Wai Cheong Yip
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore
- NUS Centre for Cancer Research (N2CR), MD6, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore, 117599, Singapore
| | - Min En Nga
- Department of Pathology, National University Hospital, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Susan Swee Shan Hue
- Department of Pathology, National University Hospital, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore
| | - Thomas Choudary Putti
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Boon Huat Bay
- Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore
| | - Qingsong Lin
- Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore
| | - Lihan Zhou
- MiRXES Pte Ltd, JTC MedTech Hub, 2 Tukang Innovation Grove #08-01, Singapore, 618305, Singapore
| | - Mikael Hartman
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 8, Singapore, 119228, Singapore
| | - Tze Ping Loh
- Department of Laboratory Medicine, National University Hospital, Level 3 NUH Main Building, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Manikandan Lakshmanan
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore
| | - Sook Yee Lee
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore
| | - Vinay Tergaonkar
- NUS Centre for Cancer Research (N2CR), MD6, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore, 117599, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore
| | - Huiwen Chua
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Adeline Voon Hui Lee
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Eric Yew Meng Yeo
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Mo-Huang Li
- CellSievo Pte Ltd, Block 289A, Bukit Batok Street 25, #15-218, Singapore, 650289, Singapore
| | - Chan Fong Chang
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore, 117594, Singapore
| | - Zizheng Kee
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore
| | - Karen Mei-Ling Tan
- Department of Laboratory Medicine, National University Hospital, Level 3 NUH Main Building, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
- Singapore Institute For Clinical Sciences, Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore, 117609, Singapore.
| | - Soo Yong Tan
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore.
- NUS Centre for Cancer Research (N2CR), MD6, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore, 117599, Singapore.
- Department of Pathology, National University Hospital, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore.
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, 61 Biopolis Drive, Singapore, 138673, Singapore.
| | - Evelyn Siew-Chuan Koay
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore.
- Department of Laboratory Medicine, National University Hospital, Level 3 NUH Main Building, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
| | - Marco Archetti
- Department of Biology, Pennsylvania State University, W210 Millennium Science Complex, University Park, PA, 16802, USA.
| | - Sai Mun Leong
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Level 3 NUH Main Building, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore.
- NUS Centre for Cancer Research (N2CR), MD6, Centre for Translational Medicine, National University of Singapore, 14 Medical Drive, #12-01, Singapore, 117599, Singapore.
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13
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Keup C, Kimmig R, Kasimir-Bauer S. The Diversity of Liquid Biopsies and Their Potential in Breast Cancer Management. Cancers (Basel) 2023; 15:5463. [PMID: 38001722 PMCID: PMC10670968 DOI: 10.3390/cancers15225463] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 11/10/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Analyzing blood as a so-called liquid biopsy in breast cancer (BC) patients has the potential to adapt therapy management. Circulating tumor cells (CTCs), extracellular vesicles (EVs), cell-free DNA (cfDNA) and other blood components mirror the tumoral heterogeneity and could support a range of clinical decisions. Multi-cancer early detection tests utilizing blood are advancing but are not part of any clinical routine yet. Liquid biopsy analysis in the course of neoadjuvant therapy has potential for therapy (de)escalation.Minimal residual disease detection via serial cfDNA analysis is currently on its way. The prognostic value of blood analytes in early and metastatic BC is undisputable, but the value of these prognostic biomarkers for clinical management is controversial. An interventional trial confirmed a significant outcome benefit when therapy was changed in case of newly emerging cfDNA mutations under treatment and thus showed the clinical utility of cfDNA analysis for therapy monitoring. The analysis of PIK3CA or ESR1 variants in plasma of metastatic BC patients to prescribe targeted therapy with alpesilib or elacestrant has already arrived in clinical practice with FDA-approved tests available and is recommended by ASCO. The translation of more liquid biopsy applications into clinical practice is still pending due to a lack of knowledge of the analytes' biology, lack of standards and difficulties in proving clinical utility.
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Affiliation(s)
- Corinna Keup
- Department of Gynecology and Obstetrics, University Hospital of Essen, 45147 Essen, Germany
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14
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Chamandi G, El-Hajjar L, El Kurdi A, Le Bras M, Nasr R, Lehmann-Che J. ER Negative Breast Cancer and miRNA: There Is More to Decipher Than What the Pathologist Can See! Biomedicines 2023; 11:2300. [PMID: 37626796 PMCID: PMC10452617 DOI: 10.3390/biomedicines11082300] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/03/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Breast cancer (BC), the most prevalent cancer in women, is a heterogenous disease. Despite advancements in BC diagnosis, prognosis, and therapeutics, survival rates have drastically decreased in the metastatic setting. Therefore, BC still remains a medical challenge. The evolution of high-throughput technology has highlighted gaps in the classification system of BCs. Of particular interest is the notorious triple negative BC, which was recounted as being heterogenous itself and it overlaps with distinct subtypes, namely molecular apocrine (MA) and luminal androgen (LAR) BCs. These subtypes are, even today, still misdiagnosed and poorly treated. As such, researchers and clinicians have been looking for ways through which to refine BC classification in order to properly understand the initiation, development, progression, and the responses to the treatment of BCs. One tool is biomarkers and, specifically, microRNA (miRNA), which are highly reported as associated with BC carcinogenesis. In this review, the diverse roles of miRNA in estrogen receptor negative (ER-) and androgen receptor positive (AR+) BC are depicted. While highlighting their oncogenic and tumor suppressor functions in tumor progression, we will discuss their diagnostic, prognostic, and predictive biomarker potentials, as well as their drug sensitivity/resistance activity. The association of several miRNAs in the KEGG-reported pathways that are related to ER-BC carcinogenesis is presented. The identification and verification of accurate miRNA panels is a cornerstone for tackling BC classification setbacks, as is also the deciphering of the carcinogenesis regulators of ER - AR + BC.
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Affiliation(s)
- Ghada Chamandi
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, 11-0236 Beirut, Lebanon; (G.C.); (L.E.-H.)
- Pathophysiology of Breast Cancer Team, INSERM U976, Immunologie Humaine, Pathophysiologie, Immunothérapie (HIPI), Université Paris Cité, 75010 Paris, France;
| | - Layal El-Hajjar
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, 11-0236 Beirut, Lebanon; (G.C.); (L.E.-H.)
- Office of Basic/Translational Research and Graduate Studies, Faculty of Medicine, American University of Beirut, 11-0236 Beirut, Lebanon
| | - Abdallah El Kurdi
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, 11-0236 Beirut, Lebanon;
| | - Morgane Le Bras
- Pathophysiology of Breast Cancer Team, INSERM U976, Immunologie Humaine, Pathophysiologie, Immunothérapie (HIPI), Université Paris Cité, 75010 Paris, France;
| | - Rihab Nasr
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, 11-0236 Beirut, Lebanon; (G.C.); (L.E.-H.)
| | - Jacqueline Lehmann-Che
- Pathophysiology of Breast Cancer Team, INSERM U976, Immunologie Humaine, Pathophysiologie, Immunothérapie (HIPI), Université Paris Cité, 75010 Paris, France;
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15
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Gupta J, Suliman M, Ali R, Margiana R, Hjazi A, Alsaab HO, Qasim MT, Hussien BM, Ahmed M. Double-edged sword role of miRNA-633 and miRNA-181 in human cancers. Pathol Res Pract 2023; 248:154701. [PMID: 37542859 DOI: 10.1016/j.prp.2023.154701] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/16/2023] [Accepted: 07/18/2023] [Indexed: 08/07/2023]
Abstract
Understanding the function and mode of operation of microRNAs (miRNAs) in cancer is of growing interest. The short non-coding RNAs known as miRNAs, which target mRNA in multicellular organisms, are described as controlling essential cellular processes. The miR-181 family and miR-633 are well-known miRNAs that play a key role in the development and metastasis of tumor cells. They may facilitate either tumor-suppressive or oncogenic function in malignant cells, according to mounting evidence. Metastatic cells that are closely linked to cancer cell migration, invasion, and angiogenesis can be identified by abnormal levels of miR-181 and miR-633. Numerous studies have demonstrated their capacity to control drug resistance, cell growth, apoptosis, and the epithelial-mesenchymal transition (EMT) and metastasis process. Interestingly, the levels of miR-181 and miR-633 and their potential target genes in the basic cellular process can vary depending on the type of cancer cells and their gene expression profile. Such miRNAs' interactions with other non-coding RNAs such as long non-coding RNAs and circular RNAs can influence tumor behaviors. Herein, we concentrated on the multifaceted roles of miR-181 and miR-633 and potential targets in human tumorigenesis, ranging from cell growth and metastasis to drug resistance.
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Affiliation(s)
- Jitendra Gupta
- Institute of Pharmaceutical Research, GLA University, Mathura 281406, U. P., India.
| | - Muath Suliman
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Rida Ali
- Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Ria Margiana
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Master's Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Andrology Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
| | - Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Hashem O Alsaab
- Department of Pharmaceutics and Pharmaceutical Technology, Taif University, Taif, Saudi Arabia
| | - Maytham T Qasim
- Department of Anesthesia, College of Health and Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq
| | - Beneen M Hussien
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Muhja Ahmed
- Medical Technical College, Al-Farahidi University, Baghdad, Iraq
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16
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Singh S, Saini H, Sharma A, Gupta S, Huddar VG, Tripathi R. Breast cancer: miRNAs monitoring chemoresistance and systemic therapy. Front Oncol 2023; 13:1155254. [PMID: 37397377 PMCID: PMC10312137 DOI: 10.3389/fonc.2023.1155254] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 06/05/2023] [Indexed: 07/04/2023] Open
Abstract
With a high mortality rate that accounts for millions of cancer-related deaths each year, breast cancer is the second most common malignancy in women. Chemotherapy has significant potential in the prevention and spreading of breast cancer; however, drug resistance often hinders therapy in breast cancer patients. The identification and the use of novel molecular biomarkers, which can predict response to chemotherapy, might lead to tailoring breast cancer treatment. In this context, accumulating research has reported microRNAs (miRNAs) as potential biomarkers for early cancer detection, and are conducive to designing a more specific treatment plan by helping analyze drug resistance and sensitivity in breast cancer treatment. In this review, miRNAs are discussed in two alternative ways-as tumor suppressors to be used in miRNA replacement therapy to reduce oncogenesis and as oncomirs to lessen the translation of the target miRNA. Different miRNAs like miR-638, miR-17, miR-20b, miR-342, miR-484, miR-21, miR-24, miR-27, miR-23 and miR-200 are involved in the regulation of chemoresistance through diverse genetic targets. For instance, tumor-suppressing miRNAs like miR-342, miR-16, miR-214, and miR-128 and tumor-promoting miRNAs like miR101 and miR-106-25 cluster regulate the cell cycle, apoptosis, epithelial to mesenchymal transition and other pathways to impart breast cancer drug resistance. Hence, in this review, we have discussed the significance of miRNA biomarkers that could assist in providing novel therapeutic targets to overcome potential chemotherapy resistance to systemic therapy and further facilitate the design of tailored therapy for enhanced efficacy against breast cancer.
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Affiliation(s)
- Shivam Singh
- Department of Radiation Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Heena Saini
- Integrated translational Molecular Biology laboratory, Department of Rog Nidan and Vikriti vigyan (Pathology), All India Institute of Ayurveda (AIIA), New Delhi, India
| | - Ashok Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Subhash Gupta
- Department of Radiation Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - V. G. Huddar
- Department of Kaya Chikitsa (Internal Medicine), All India Institute of Ayurveda (AIIA), New Delhi, India
| | - Richa Tripathi
- Integrated translational Molecular Biology laboratory, Department of Rog Nidan and Vikriti vigyan (Pathology), All India Institute of Ayurveda (AIIA), New Delhi, India
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17
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Szczepanek J, Skorupa M, Jarkiewicz-Tretyn J, Cybulski C, Tretyn A. Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA. Int J Mol Sci 2023; 24:ijms24087235. [PMID: 37108398 PMCID: PMC10138995 DOI: 10.3390/ijms24087235] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/24/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.
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Affiliation(s)
- Joanna Szczepanek
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Torun, Poland
| | - Monika Skorupa
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Torun, Poland
- Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Torun, Poland
| | | | - Cezary Cybulski
- International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, 70-204 Szczecin, Poland
| | - Andrzej Tretyn
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Torun, Poland
- Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Torun, Poland
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18
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Potential Role of Circulating miRNAs for Breast Cancer Management in the Neoadjuvant Setting: A Road to Pave. Cancers (Basel) 2023; 15:cancers15051410. [PMID: 36900200 PMCID: PMC10000233 DOI: 10.3390/cancers15051410] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/20/2023] [Accepted: 02/21/2023] [Indexed: 02/25/2023] Open
Abstract
Recently, circulating microRNAs (miRNAs) have emerged as potential non-invasive biomarkers for breast cancer (BC) management. In the context of BC patients undergoing neoadjuvant chemotherapy (NAC), the possibility of obtaining repeated, non-invasive biological samples from patients before, during, and after treatment is incredibly convenient and provides the opportunity to investigate circulating miRNAs as diagnostic, predictive, and prognostic tools. The present review aims to summarize major findings in this setting, thus highlighting their potential applicability in daily clinical practice and their possible limitations. In all the contexts (diagnostic, predictive, and prognostic), circulating miR-21-5p and miR-34a-5p have emerged as the most promising non-invasive biomarkers for BC patients undergoing NAC. Specifically, their high baseline level could discriminate between BC patients and healthy controls. On the other hand, in predictive and prognostic investigations, low circulating miR-21-5p and miR-34a-5p levels may identify patients with better outcomes, in terms of both treatment response and invasive disease-free survival. However, the findings in this field have been very heterogeneous. Indeed, pre-analytical and analytical variables, as well as factors related to patients, may explain the inconsistency among different study results. Thus, further clinical trials, with more precise patient inclusion criteria and more standardized methodological approaches, are definitely needed to better define the potential role of these promising non-invasive biomarkers.
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Tarighati E, Keivan H, Mahani H. A review of prognostic and predictive biomarkers in breast cancer. Clin Exp Med 2023; 23:1-16. [PMID: 35031885 DOI: 10.1007/s10238-021-00781-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 12/01/2021] [Indexed: 12/12/2022]
Abstract
Breast cancer (BC) is a common cancer all over the world that affects women. BC is one of the leading causes of cancer mortality in women, which today has decreased with the advancement of technology and new diagnostic and therapeutic methods. BCs are histologically divided into in situ and invasive carcinoma, and both of them can be divided into ductal and lobular. The main function after the diagnosis of invasive breast cancer is which patient should use chemotherapy, which patient should receive adjuvant therapy, and which should not. If the decision is for adjuvant therapy, the next challenge is to identify the most appropriate treatment or combination of treatments for a particular patient. Addressing the first challenge can be helped by prognostic biomarkers, while addressing the second challenge can be done by predictive biomarkers. Among the molecular markers related to BC, ER, PR, HER2, and the Mib1/Ki-67 proliferation index are the most significant ones and are tightly confirmed in the standard care of all primary, recurrent, and metastatic BC patients. CEA and CA-15-3 antigens are the most valuable markers of serum tumors in BC patients. Determining the series of these markers helps monitor response to the treatment and early detection of recurrence or metastasis. miRNAs have been demonstrated to be intricate in mammary gland growth, proliferation, and formation of BC known to be incriminated in BC biology. By combining established prognostic factors with valid prognostic/predicted biomarkers, we can start the journey to personalized treatment for every recently diagnosed BC patient.
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Affiliation(s)
- Elaheh Tarighati
- Department of Medical Physics, Iran University of Medical Sciences, Tehran, Iran
| | - Hadi Keivan
- School of Paramedicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Hojjat Mahani
- Radiation Applications Research School, Nuclear Science and Technology Research Institute, P.O. Box: 14395-836, Tehran, Iran.
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20
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Rajput S, Sharma PK, Malviya R. Biomarkers and Treatment Strategies for Breast Cancer Recurrence. Curr Drug Targets 2023; 24:1209-1220. [PMID: 38164731 DOI: 10.2174/0113894501258059231103072025] [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: 04/15/2023] [Revised: 07/14/2023] [Accepted: 10/03/2023] [Indexed: 01/03/2024]
Abstract
Despite recent treatment advancements, breast cancer remains a life-threatening disease. Although treatment is successful in the early stages, a significant proportion of individuals with breast cancer eventually experience a recurrence of the disease. Breast tumour recurrence poses a significant medical issue. Despite tumours being a primary cause of mortality, there remains a limited understanding of the fundamental mechanisms underlying tumour recurrence. The majority of the time, after surgery or medical treatment, this metastatic disease manifests itself after the disease is undiagnosed for a considerable amount of time. This phenomenon is commonly referred to as a relapse or recurrence. Metastatic breast cancer has the potential to recur at varying intervals, ranging from a few months to several decades following the initial diagnosis and treatment. This article aimed to summarise the primary causes of breast cancer recurrence and highlight the key issues that need to be addressed in order to effectively decrease the mortality rate among breast cancer patients. This article discusses various therapeutic approaches currently employed and emerging treatment strategies that hold the potential for the complete cure of cancer.
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Affiliation(s)
- Shivam Rajput
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Pramod Kumar Sharma
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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21
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Yao J, Li G, Zhou L, Xu S, Song K, Zhang H, Zhang X, Shuai J, Ye F, Li M, Chen G, Liu H, Shaw P, Liu L. 3D collagen microchamber arrays for combined chemotherapy effect evaluation on cancer cell numbers and migration. BIOMICROFLUIDICS 2023; 17:014101. [PMID: 36619874 PMCID: PMC9812516 DOI: 10.1063/5.0121952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 12/05/2022] [Indexed: 06/17/2023]
Abstract
Breast cancer metastasis involves complex mechanisms, particularly when patients are undergoing chemotherapy. In tissues, tumor cells encounter cell-cell interactions, cell-microenvironment interactions, complex nutrient, and drug gradients. Currently, two-dimensional cell culture systems and animal models are challenging to observe and analyze cell responses to microenvironments with various physical and bio-chemical conditions, and microfluidic technology has been systematically developed to address this dilemma. In this study, we have constructed a combined chemotherapy evaluation chip (CCEC) based on microfluidic technology. The chip possesses 192 diamond-shaped microchambers containing MDA-MB-231-RFP cells, and each microchamber is composed of collagen to mimic breast cancer and its surrounding microenvironment. In addition, by adding medium containing different drugs to the medium channels of CCEC, composite drug (paclitaxel+gemcitabine+7rh and paclitaxel+fluorouracil+PP2) concentration gradients, and single drug (paclitaxel, gemcitabine, 7rh, fluorouracil, PP2) concentration gradients have been established in the five collagen regions, respectively, so that each localized microchamber in the regions has a unique drug microenvironment. In this way, we evaluated the composite and single chemotherapy efficacy on the same chip by statistically analyzing their effects on the numbers and migration of the cell. The quantitative results in CCECs reveal that the inhibition effects on the numbers and migration of MDA-MB-231-RFP cell under the composite drug gradients are more optimal than those of the single drugs. Besides, the cancer cell inhibition effect between the groups composed of two drugs has also been compared, that is the paclitaxel+gemcitabine, paclitaxel+fluorouracil, and paclitaxel+PP2 have better cell numbers and migration inhibition effects than paclitaxel+7rh. The results indicate that the bio-mimetic and high-throughput combined chemotherapy evaluation platform can serve as a more efficient and accurate tool for preclinical drug development and screening.
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Affiliation(s)
- Jingru Yao
- Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China
| | - Guoqiang Li
- Chongqing Key Laboratory of Environmental Materials and Remediation Technologies, College of Chemistry and Environmental Engineering (Chongqing University of Arts and Sciences), Chongqing 402160, People’s Republic of China
| | - Lianjie Zhou
- Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China
| | - Shuyan Xu
- Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China
| | - Kena Song
- College of Medical Technology and Engineering, Henan University of Science and Technology, Henan 471023, China
| | - Hongfei Zhang
- Hygeia International Cancer Hospital, Chongqing 401331, China
| | - Xianquan Zhang
- Hygeia International Cancer Hospital, Chongqing 401331, China
| | | | | | - Ming Li
- Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
| | - Guo Chen
- Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China
| | - He Liu
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China
| | - Peter Shaw
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China
| | - Liyu Liu
- Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China
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22
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Addressing the Clinical Feasibility of Adopting Circulating miRNA for Breast Cancer Detection, Monitoring and Management with Artificial Intelligence and Machine Learning Platforms. Int J Mol Sci 2022; 23:ijms232315382. [PMID: 36499713 PMCID: PMC9736108 DOI: 10.3390/ijms232315382] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/24/2022] [Accepted: 11/28/2022] [Indexed: 12/12/2022] Open
Abstract
Detecting breast cancer (BC) at the initial stages of progression has always been regarded as a lifesaving intervention. With modern technology, extensive studies have unraveled the complexity of BC, but the current standard practice of early breast cancer screening and clinical management of cancer progression is still heavily dependent on tissue biopsies, which are invasive and limited in capturing definitive cancer signatures for more comprehensive applications to improve outcomes in BC care and treatments. In recent years, reviews and studies have shown that liquid biopsies in the form of blood, containing free circulating and exosomal microRNAs (miRNAs), have become increasingly evident as a potential minimally invasive alternative to tissue biopsy or as a complement to biomarkers in assessing and classifying BC. As such, in this review, the potential of miRNAs as the key BC signatures in liquid biopsy are addressed, including the role of artificial intelligence (AI) and machine learning platforms (ML), in capitalizing on the big data of miRNA for a more comprehensive assessment of the cancer, leading to practical clinical utility in BC management.
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Li Z, Xiao H, Li J, Yang Z, Jiang J, Ji J, Peng C, He Y. Graphene Oxide-Based Highly Sensitive Assay of Circulating MicroRNAs for Early Prediction of the Response to Neoadjuvant Chemotherapy in Breast Cancer. Anal Chem 2022; 94:16254-16264. [DOI: 10.1021/acs.analchem.2c04117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Zhijia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Hongtao Xiao
- Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Junjie Li
- Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Zhongzhu Yang
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jun Jiang
- Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Juan Ji
- Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital affiliated to School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yang He
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
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24
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MicroRNA-Based Diagnosis and Therapy. Int J Mol Sci 2022; 23:ijms23137167. [PMID: 35806173 PMCID: PMC9266664 DOI: 10.3390/ijms23137167] [Citation(s) in RCA: 313] [Impact Index Per Article: 104.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 12/14/2022] Open
Abstract
MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.
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25
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miRNAs as therapeutic predictors and prognostic biomarkers of neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat 2022; 194:483-505. [PMID: 35727379 DOI: 10.1007/s10549-022-06642-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 05/30/2022] [Indexed: 11/02/2022]
Abstract
PURPOSE Accumulating evidence has shown that microRNAs (miRNAs) are promising biomarkers of neoadjuvant chemotherapy (NAC) response in breast cancer (BC). However, their predictive roles remain controversial. Thus, this systematic review and meta-analysis aimed to describe the role of miRNA expression in NAC response and prognosis in BC to increase statistical power and improve translation. METHODS A systematic review of electronic databases for relevant studies was conducted following PRISMA guidelines. Data were extracted, collated, and combined by odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) to estimate the strength of the associations. RESULTS Of the 560 articles screened, 59 studies were included in our systematic review, and 5 studies were included in the subsequent meta-analysis. Sixty of 123 miRNAs were found to be related with NAC response and an elevated baseline miR-7 level in tissues was associated with a higher pathological complete response rate (OR 5.63; 95% CI 2.15-14.79; P = 0.0004). The prognostic value of 39 miRNAs was also studied. Of them, 26 miRNAs were found to be associated with survival. Pooled HRs indicated that patients with increased levels of serum miR-21 from baseline to the end of the second NAC cycle and from baseline to the end of NAC had a worse disease-free survival than those with decreased levels. CONCLUSION Our results highlight that a large number of miRNAs have possible associations with NAC response and prognosis in BC patients. Further well-designed studies are needed to elucidate the molecular mechanisms underlying these associations.
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26
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Cardinali B, Tasso R, Piccioli P, Ciferri MC, Quarto R, Del Mastro L. Circulating miRNAs in Breast Cancer Diagnosis and Prognosis. Cancers (Basel) 2022; 14:cancers14092317. [PMID: 35565446 PMCID: PMC9101355 DOI: 10.3390/cancers14092317] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/22/2022] [Accepted: 04/28/2022] [Indexed: 11/16/2022] Open
Abstract
Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice.
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Affiliation(s)
- Barbara Cardinali
- Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (P.P.); (L.D.M.)
- Correspondence: ; Tel.: +39-010-555-8101
| | - Roberta Tasso
- Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy; (R.T.); (M.C.C.); (R.Q.)
| | - Patrizia Piccioli
- Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (P.P.); (L.D.M.)
| | - Maria Chiara Ciferri
- Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy; (R.T.); (M.C.C.); (R.Q.)
| | - Rodolfo Quarto
- Department of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy; (R.T.); (M.C.C.); (R.Q.)
- Cellular Oncology Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
| | - Lucia Del Mastro
- Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy; (P.P.); (L.D.M.)
- Department of Internal Medicine and Medical Specialties (DIMI), University of Genova, 16132 Genova, Italy
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27
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Wang X, Wang S. Identification of key genes involved in tamoxifen-resistant breast cancer using bioinformatics analysis. Transl Cancer Res 2022; 10:5246-5257. [PMID: 35116374 PMCID: PMC8798269 DOI: 10.21037/tcr-21-1276] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 11/03/2021] [Indexed: 11/16/2022]
Abstract
Background The purpose of the present study was to investigate the molecular mechanisms of tamoxifen resistance in breast cancer and to identify potential targets for antitamoxifen resistance. Methods Differentially expressed genes (DEGs) in tamoxifen-resistant and tamoxifen-sensitive breast cancer cells were assessed using the GSE67916 dataset acquired from the Gene Expression Omnibus database. Gene ontology (GO) and pathway enrichment analyses were applied to investigate the functions and pathways of the DEGs. Subsequently, the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING), and subnetworks were further analyzed by Molecular Complex Detection (MCODE). The PPI network and subnetworks were visualized using Cytoscape software. Results In total, 438 DEGs were identified, of which 300 were upregulated and 138 were downregulated. The DEGs were significantly enriched in the protein binding, cellular response to estradiol stimulus, and immune response GO terms while the most significant pathways included the mitogen-activated protein kinase (MAPK) signaling pathway in cancer. The PPI network of DEGs was constructed with 288 nodes and 629 edges, and 2 subnetworks were screened out from the entire network. Conclusions A number of significant hub DEGs were identified based on their degree of connectivity in the PPI network, , included MAPK1 (node degree 36), ESR1 (node degree 27), SMARCA4 (node degree 27), RANBP2 (node degree 25), and PRKCA (node degree 21). These critical hub genes were found to be related to tamoxifen resistance in breast cancer. The results of this study further the understanding of tamoxifen resistance at the molecular level and identify potential therapeutic targets for tamoxifen-resistant breast cancer.
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Affiliation(s)
- Xiaopeng Wang
- Department of Outpatient and Emergency, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Shixia Wang
- Department of Outpatient and Emergency, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China
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28
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Marima R, Francies FZ, Hull R, Molefi T, Oyomno M, Khanyile R, Mbatha S, Mabongo M, Owen Bates D, Dlamini Z. MicroRNA and Alternative mRNA Splicing Events in Cancer Drug Response/Resistance: Potent Therapeutic Targets. Biomedicines 2021; 9:1818. [PMID: 34944633 PMCID: PMC8698559 DOI: 10.3390/biomedicines9121818] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/24/2021] [Accepted: 11/29/2021] [Indexed: 12/24/2022] Open
Abstract
Cancer is a multifaceted disease that involves several molecular mechanisms including changes in gene expression. Two important processes altered in cancer that lead to changes in gene expression include altered microRNA (miRNA) expression and aberrant splicing events. MiRNAs are short non-coding RNAs that play a central role in regulating RNA silencing and gene expression. Alternative splicing increases the diversity of the proteome by producing several different spliced mRNAs from a single gene for translation. MiRNA expression and alternative splicing events are rigorously regulated processes. Dysregulation of miRNA and splicing events promote carcinogenesis and drug resistance in cancers including breast, cervical, prostate, colorectal, ovarian and leukemia. Alternative splicing may change the target mRNA 3'UTR binding site. This alteration can affect the produced protein and may ultimately affect the drug affinity of target proteins, eventually leading to drug resistance. Drug resistance can be caused by intrinsic and extrinsic factors. The interplay between miRNA and alternative splicing is largely due to splicing resulting in altered 3'UTR targeted binding of miRNAs. This can result in the altered targeting of these isoforms and altered drug targets and drug resistance. Furthermore, the increasing prevalence of cancer drug resistance poses a substantial challenge in the management of the disease. Henceforth, molecular alterations have become highly attractive drug targets to reverse the aberrant effects of miRNAs and splicing events that promote malignancy and drug resistance. While the miRNA-mRNA splicing interplay in cancer drug resistance remains largely to be elucidated, this review focuses on miRNA and alternative mRNA splicing (AS) events in breast, cervical, prostate, colorectal and ovarian cancer, as well as leukemia, and the role these events play in drug resistance. MiRNA induced cancer drug resistance; alternative mRNA splicing (AS) in cancer drug resistance; the interplay between AS and miRNA in chemoresistance will be discussed. Despite this great potential, the interplay between aberrant splicing events and miRNA is understudied but holds great potential in deciphering miRNA-mediated drug resistance.
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Affiliation(s)
- Rahaba Marima
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
| | - Flavia Zita Francies
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
| | - Rodney Hull
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
| | - Thulo Molefi
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
- Department of Medical Oncology, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Meryl Oyomno
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
- Department of Surgery, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Richard Khanyile
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
- Department of Medical Oncology, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Sikhumbuzo Mbatha
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
- Department of Surgery, Steve Biko Academic Hospital, University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - Mzubanzi Mabongo
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
- Department of Maxillofacial and Oral Surgery, School of Dentistry, University of Pretoria, Hatfield, Pretoria 0028, South Africa
| | - David Owen Bates
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
- Centre for Cancer Sciences, Division of Cancer and Stem Cells, Biodiscovery Institute, University of Nottingham, Nottingham NG7 2RD, UK
| | - Zodwa Dlamini
- SAMRC Precision Oncology Research Unit (PORU), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfiel, Pretoria 0028, South Africa; (R.M.); (F.Z.F.); (R.H.); (T.M.); (M.O.); (R.K.); (S.M.); (M.M.); (D.O.B.)
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29
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Zhang Z, Zhang H, Li C, Xiang Q, Xu L, Liu Q, Pang X, Zhang W, Zhang H, Zhang S, Duan X, Liu Y, Cui Y. Circulating microRNAs as indicators in the prediction of neoadjuvant chemotherapy response in luminal B breast cancer. Thorac Cancer 2021; 12:3396-3406. [PMID: 34751517 PMCID: PMC8671904 DOI: 10.1111/1759-7714.14219] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 10/19/2021] [Accepted: 10/20/2021] [Indexed: 12/25/2022] Open
Abstract
PURPOSE Circulating microRNAs (miRNAs) have been indicated as predictive biomarker for the response to neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer (BC); however, to date the conclusions have been controversial. The biological characteristics of BC were affected by molecular subtypes. Hence, we aimed to investigate the predictive effect of miRNAs on NAC response in luminal B BC patients. METHODS Thirty-seven luminal B BC patient under NAC were prospectively enrolled in this study. Based on their clinical, pathological, and comprehensive response, the patients were defined as responder or non-responders, respectively. Circulating miRNAs were isolated from blood samples before and at the middle of NAC, and candidate miRNAs (miR-34a-5p, miR-125b-5p, miR-210, miR-222, miR-375, miR-718, miR-4516, and let-7g) were analyzed by quantitative real-time polymerase chain reaction (PCR). In addition, the association between miRNAs and disease-free survival (DFS) was examined. RESULTS miR-718, miR-4516, miR-210, and miR-125b-5p were found to be specific miRNAs associated with chemo-sensitivity of luminal B HER2 negative patients (n = 24). In the luminal B HER2 positive cohort (n = 13), dynamics of miR-222 and let-7g correlated with pathological response. Treatment-induced increase in miR-34a-5p in the responders except who reached pathologic complete response (pCR) was consistently identified across all luminal B patients and its two subgroups. Finally, after adjustments for Neo-Bioscore, patients with increased levels of miR-125b-5p during NAC had a worse DFS than those with decreased levels (HR = 5.86, 95% CI = 1.39-24.62, p = 0.016). CONCLUSION Specific circulating miRNAs were identified as predictive markers for NAC response and prognosis in luminal B BC. The underlying mechanism needs further studies.
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Affiliation(s)
- Zhuo Zhang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Hanxu Zhang
- Department of Pharmacy, Peking University First Hospital, Beijing, China.,School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
| | - Chao Li
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Qian Xiang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Ling Xu
- Breast Disease Center, Peking University First Hospital, Beijing, China
| | - Qianxin Liu
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Xiaocong Pang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Wenjia Zhang
- Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Hong Zhang
- Department of Pathology, Peking University First Hospital, Beijing, China
| | - Shuang Zhang
- Department of Pathology, Peking University First Hospital, Beijing, China
| | - Xuening Duan
- Breast Disease Center, Peking University First Hospital, Beijing, China
| | - Yinhua Liu
- Breast Disease Center, Peking University First Hospital, Beijing, China
| | - Yimin Cui
- Department of Pharmacy, Peking University First Hospital, Beijing, China.,School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China.,Institute of Clinical Pharmacology, Peking University, Beijing, China
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30
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Ahmed KT, Sun J, Chen W, Martinez I, Cheng S, Zhang W, Yong J, Zhang W. In silico model for miRNA-mediated regulatory network in cancer. Brief Bioinform 2021; 22:bbab264. [PMID: 34279571 PMCID: PMC8575005 DOI: 10.1093/bib/bbab264] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/19/2021] [Accepted: 06/21/2021] [Indexed: 12/12/2022] Open
Abstract
Deregulation of gene expression is associated with the pathogenesis of numerous human diseases including cancer. Current data analyses on gene expression are mostly focused on differential gene/transcript expression in big data-driven studies. However, a poor connection to the proteome changes is a widespread problem in current data analyses. This is partly due to the complexity of gene regulatory pathways at the post-transcriptional level. In this study, we overcome these limitations and introduce a graph-based learning model, PTNet, which simulates the microRNAs (miRNAs) that regulate gene expression post-transcriptionally in silico. Our model does not require large-scale proteomics studies to measure the protein expression and can successfully predict the protein levels by considering the miRNA-mRNA interaction network, the mRNA expression, and the miRNA expression. Large-scale experiments on simulations and real cancer high-throughput datasets using PTNet validated that (i) the miRNA-mediated interaction network affects the abundance of corresponding proteins and (ii) the predicted protein expression has a higher correlation with the proteomics data (ground-truth) than the mRNA expression data. The classification performance also shows that the predicted protein expression has an improved prediction power on cancer outcomes compared to the prediction done by the mRNA expression data only or considering both mRNA and miRNA. Availability: PTNet toolbox is available at http://github.com/CompbioLabUCF/PTNet.
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Affiliation(s)
| | - Jiao Sun
- Department of Computer Science, University of Central Florida, Orlando, FL 32816, USA
| | - William Chen
- Department of Computer Science, University of Central Florida, Orlando, FL 32816, USA
| | - Irene Martinez
- Department of Molecular Biotechnology, Universität Heidelberg, Heidelberg, 69120, Germany
| | - Sze Cheng
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA
| | - Wencai Zhang
- Division of Cancer Research, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA
| | - Jeongsik Yong
- Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Twin Cities, Minneapolis, MN 55455, USA
| | - Wei Zhang
- Department of Computer Science, University of Central Florida, Orlando, FL 32816, USA
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31
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Davey MG, Lowery AJ, Miller N, Kerin MJ. MicroRNA Expression Profiles and Breast Cancer Chemotherapy. Int J Mol Sci 2021; 22:10812. [PMID: 34639152 PMCID: PMC8509379 DOI: 10.3390/ijms221910812] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 10/01/2021] [Accepted: 10/05/2021] [Indexed: 02/06/2023] Open
Abstract
Breast cancer is the most common malignancy diagnosed in women. Traditionally, radical surgical resection was the cornerstone of breast cancer management, with limited exceptions. In recent times, our enhanced appreciation of the biomolecular characteristics of breast cancer has transformed the treatment paradigm to include prescription of chemotherapeutical agents, radiotherapies, targeted therapies, as well as more refined surgical approaches. While treatments with such modalities have enhanced clinico-oncological outcomes for breast cancer patients, the efforts of oncological and translational research have concentrated on the identification of novel biomarkers which may successfully inform prognosis and response to therapies, improve current therapeutic strategies, and enhance prognostication. Mi(cro)RNAs are small, non-coding molecules which are known to play regulatory roles in governing gene expression and cellular activity. Measurement of miRNA expression profiles have been illustrated to inform the response to therapies, such as conventional chemotherapy, and are currently undergoing assessment as means of enhancing treatment strategies with these cytotoxic agents. Herein, this review outlines how chemotherapy prescription has revolutionised breast cancer treatment and illustrates the novel role of miRNAs as biomarkers capable of enhancing current therapeutic strategies using chemotherapy in patients being treated with curative intent for breast cancer.
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Affiliation(s)
- Matthew G. Davey
- Department of Surgery, The Lambe Institute for Translational Research, National University of Ireland, Galway, H91 YR71 Galway, Ireland; (A.J.L.); (N.M.); (M.J.K.)
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32
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Isca C, Piacentini F, Mastrolia I, Masciale V, Caggia F, Toss A, Piombino C, Moscetti L, Barbolini M, Maur M, Dominici M, Omarini C. Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature. Cancers (Basel) 2021; 13:cancers13194894. [PMID: 34638377 PMCID: PMC8508299 DOI: 10.3390/cancers13194894] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 09/24/2021] [Accepted: 09/27/2021] [Indexed: 12/12/2022] Open
Abstract
MicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value.
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Affiliation(s)
- Chrystel Isca
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
| | - Federico Piacentini
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
| | - Ilenia Mastrolia
- Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy; (I.M.); (V.M.)
| | - Valentina Masciale
- Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy; (I.M.); (V.M.)
| | - Federica Caggia
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
| | - Angela Toss
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
| | - Claudia Piombino
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
| | - Luca Moscetti
- Division of Medical Oncology, Department of Oncology-Hematology, University Hospital of Modena, 41124 Modena, Italy; (L.M.); (M.M.)
| | - Monica Barbolini
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
| | - Michela Maur
- Division of Medical Oncology, Department of Oncology-Hematology, University Hospital of Modena, 41124 Modena, Italy; (L.M.); (M.M.)
| | - Massimo Dominici
- Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, 41124 Modena, Italy; (C.I.); (F.P.); (F.C.); (A.T.); (C.P.); (M.B.); (M.D.)
- Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy; (I.M.); (V.M.)
| | - Claudia Omarini
- Division of Medical Oncology, Department of Oncology-Hematology, University Hospital of Modena, 41124 Modena, Italy; (L.M.); (M.M.)
- Correspondence: ; Tel.: +39-059-4222845
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Seale KN, Tkaczuk KHR. Circulating Biomarkers in Breast Cancer. Clin Breast Cancer 2021; 22:e319-e331. [PMID: 34756687 DOI: 10.1016/j.clbc.2021.09.006] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 08/22/2021] [Accepted: 09/19/2021] [Indexed: 12/11/2022]
Abstract
Breast cancer management has progressed immensely over the decades, but the disease is still a major source of morbidity and mortality worldwide. Even with enhanced imaging detection and tissue biopsy capabilities, disease can progress on an ineffective treatment before additional information is obtained through standard methods of response evaluation, including the RECIST 1.1 criteria, widely used for assessment of treatment response and benefit from therapy.6 Circulating biomarkers have the potential to provide valuable insight into disease progression and response to therapy, and they can serve to identify actionable mutations and tumor characteristics that can direct therapy. These biomarkers can be collected at higher frequencies than imaging or tissue sampling, potentially allowing for more informed management. This review will evaluate the roles of circulating biomarkers in breast cancer, including the serum markers Carcinoembryonic antigen CA15-3, CA27-29, HER2 ECD, and investigatory markers such as GP88; and the components of the liquid biopsy, including circulating tumor cells, cell free DNA/DNA methylation, circulating tumor DNA, and circulating microRNA.
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Affiliation(s)
- Katelyn N Seale
- University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, 22 South Greene Street, S9D12, Baltimore, MD 21201
| | - Katherine H R Tkaczuk
- University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Comprehensive Cancer Center, 22 South Greene Street, S9D12, Baltimore, MD 21201.
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34
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The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment. Int J Mol Sci 2021; 22:ijms22158290. [PMID: 34361056 PMCID: PMC8346977 DOI: 10.3390/ijms22158290] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/29/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
Abstract
Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment options, have aided the personalisation of breast cancer patient care. Despite this, some patients will unfortunately succumb to the disease. In recent times, translational research efforts have been focused on identifying novel biomarkers capable of informing patient outcome; microRNAs (miRNAs) are small non-coding molecules, which regulate gene expression at a post-transcriptional level. Aberrant miRNA expression profiles have been observed in cancer proliferation and development. The measurement and correlation of miRNA expression levels with oncological outcomes such as response to current conventional therapies, and disease recurrence are being investigated. Herein, we outline the clinical utility of miRNA expression profiles in informing breast cancer prognosis, predicting response to treatment strategies as well as their potential as therapeutic targets to enhance treatment modalities in the era of precision oncology.
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35
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Malczewska A, Frampton AE, Mato Prado M, Ameri S, Dabrowska AF, Zagorac S, Clift AK, Kos-Kudła B, Faiz O, Stebbing J, Castellano L, Frilling A. Circulating MicroRNAs in Small-bowel Neuroendocrine Tumors: A Potential Tool for Diagnosis and Assessment of Effectiveness of Surgical Resection. Ann Surg 2021; 274:e1-e9. [PMID: 31373926 DOI: 10.1097/sla.0000000000003502] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To discover serum-based microRNA (miRNA) biomarkers for small-bowel neuroendocrine tumors (SBNET) to help guide clinical decisions. BACKGROUND MiRNAs are small noncoding RNA molecules implicated in the initiation and progression of many cancers. MiRNAs are remarkably stable in bodily fluids, and can potentially be translated into clinically useful biomarkers. Novel biomarkers are needed in SBNET to determine disease aggressiveness, select patients for treatment, detect early recurrence, and monitor response. METHODS This study was performed in 3 stages (discovery, validation, and a prospective, longitudinal assessment). Discovery comprised of global profiling of 376 miRNA in sera from SBNET patients (n = 11) versus healthy controls (HCs; n = 3). Up-regulated miRNAs were subsequently validated in additional SBNET (n = 33) and HC sera (n = 14); and then longitudinally after SBNET resection (n = 12), with serial serum sampling (preoperatively day 0; postoperatively at 1 week, 1 month, and 12 months). RESULTS Four serum miRNAs (miR-125b-5p, -362-5p, -425-5p and -500a-5p) were significantly up-regulated in SBNET (P < 0.05; fold-change >2) based on multiple normalization strategies, and were validated by RT-qPCR. This combination was able to differentiate SBNET from HC with an area under the curve of 0.951. Longitudinal assessment revealed that miR-125b-5p returned towards HC levels at 1 month postoperatively in patients without disease, whereas remaining up-regulated in those with residual disease (RSD). This was also true at 12 months postoperatively. In addition, miR-362-5p appeared up-regulated at 12 months in RSD and recurrent disease (RCD). CONCLUSIONS Our study represents the largest global profiling of serum miRNAs in SBNET patients, and the first to evaluate ongoing serum miRNA expression changes after surgical resection. Serum miR-125b-5p and miR-362-5p have potential to be used to detect RSD/RCD.
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Affiliation(s)
- Anna Malczewska
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, Katowice, Poland
| | - Adam E Frampton
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Mireia Mato Prado
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Shima Ameri
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Aleksandra F Dabrowska
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Sladjana Zagorac
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Ashley K Clift
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Beata Kos-Kudła
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, Katowice, Poland
| | - Omar Faiz
- St. Mark's Hospital, Harrow, Middlesex, UK
| | - Justin Stebbing
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
| | - Leandro Castellano
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
- University of Sussex, School of Life Sciences, John Maynard Smith Building, Falmer, Brighton, UK
| | - Andrea Frilling
- Department of Surgery & Cancer, Imperial College, Hammersmith Hospital campus, Du Cane Road, London, UK
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Sheinboim D, Parikh S, Parikh R, Menuchin A, Shapira G, Kapitansky O, Elkoshi N, Ruppo S, Shaham L, Golan T, Elgavish S, Nevo Y, Bell RE, Malcov H, Shomron N, Taub JW, Izraeli S, Levy C. Slow transcription of the 99a/let-7c/125b-2 cluster results in differential miRNA expression and promotes melanoma phenotypic plasticity. J Invest Dermatol 2021; 141:2944-2956.e6. [PMID: 34186058 DOI: 10.1016/j.jid.2021.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 03/21/2021] [Accepted: 03/31/2021] [Indexed: 10/21/2022]
Abstract
Almost half of human miRNAs are encoded in clusters. Although transcribed as a single unit, the levels of individual mature miRNAs often differ. The mechanisms underlying differential biogenesis of clustered miRNAs and the resulting physiological implications are mostly unknown. Here, we report that the melanoma master transcription regulator MITF regulates the differential expression of the 99a/let-7c/125b-2 cluster by altering the distribution of RNA polymerase II (Pol-II) along the cluster. We discovered that MITF interacts with TRIM28, a known inhibitor of Pol-II transcription elongation, at the let-7c region resulting in Pol-II pausing and causing its elevated expression, whereas low levels of Pol-II occupation over miR-99a and miR-125b-2 regions decreases their biogenesis. Furthermore, we showed that this differential expression affects the phenotypic state of melanoma cells. RNA-seq analysis of proliferative melanoma cells that express miR-99a and miR-125b mimics revealed a transcriptomic shift toward an invasive phenotype. Conversely, expression of a let-7c mimic in invasive melanoma cells induced a shift to a more proliferative state. We confirmed direct target genes of these miRNAs: FGFR3, BAP1, Bcl2, TGFBR1, and CDKN1A. Our study demonstrates a MITF-governed biogenesis mechanism that results in differential expression of clustered 99a/let-7c/125b-2 miRNAs that control melanoma progression.
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Affiliation(s)
- Danna Sheinboim
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Shivang Parikh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Roma Parikh
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Amitai Menuchin
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Guy Shapira
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Oxana Kapitansky
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Nadav Elkoshi
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Shmuel Ruppo
- Info-CORE, Bioinformatics Unit of the I-CORE, Hebrew University of Jerusalem and Hadassah Medical Center, Jerusalem 9112102, Israel
| | - Lital Shaham
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Division of Pediatric Hematology-Oncology Department, Schneider Children's Medical Center, Petah Tikva 49202, Israel
| | - Tamar Golan
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Sharona Elgavish
- Info-CORE, Bioinformatics Unit of the I-CORE, Hebrew University of Jerusalem and Hadassah Medical Center, Jerusalem 9112102, Israel
| | - Yuval Nevo
- Info-CORE, Bioinformatics Unit of the I-CORE, Hebrew University of Jerusalem and Hadassah Medical Center, Jerusalem 9112102, Israel
| | - Rachel E Bell
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Hagar Malcov
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
| | - Noam Shomron
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Edmond J. Safra Center of Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel
| | - Jeffrey W Taub
- Wayne State University School of Medicine, Detroit, MI 48201, USA; Division of Pediatric Hematology and Oncology, Children's Hospital of Michigan, Detroit, MI 48201, USA
| | - Shai Izraeli
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Info-CORE, Bioinformatics Unit of the I-CORE, Hebrew University of Jerusalem and Hadassah Medical Center, Jerusalem 9112102, Israel
| | - Carmit Levy
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
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Nagasaka M, Uddin MH, Al-Hallak MN, Rahman S, Balasubramanian S, Sukari A, Azmi AS. Liquid biopsy for therapy monitoring in early-stage non-small cell lung cancer. Mol Cancer 2021; 20:82. [PMID: 34074295 PMCID: PMC8170728 DOI: 10.1186/s12943-021-01371-1] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 05/13/2021] [Indexed: 12/19/2022] Open
Abstract
Liquid biopsy is now considered a valuable diagnostic tool for advanced metastatic non-small cell lung cancer (NSCLC). In NSCLC, circulating tumor DNA (ctDNA) analysis has been shown to increase the chances of identifying the presence of targetable mutations and has been adopted by many clinicians owing to its low risk. Serial monitoring of ctDNA may also help assess the treatment response or for monitoring relapse. As the presence of detectable plasma ctDNA post-surgery likely indicates residual tumor burden, studies have been performed to quantify plasma ctDNA to assess minimal residual disease (MRD) in early-stage resected NSCLC. Most data on utilizing liquid biopsy for monitoring MRD in early-stage NSCLC are from small-scale studies using ctDNA. Here, we review the recent research on liquid biopsy in NSCLC, not limited to ctDNA, and focus on novel methods such as micro RNAs (miRNA) and long non-coding (lncRNA).
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Affiliation(s)
- Misako Nagasaka
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA.
- Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
| | - Mohammed Hafiz Uddin
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Mohammed Najeeb Al-Hallak
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Sarah Rahman
- Department of Cell and Molecular Biology, Grand Valley State University, Allendale, MI, 49401, USA
| | - Suresh Balasubramanian
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Ammar Sukari
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
| | - Asfar S Azmi
- Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, 4100 John R, Detroit, MI, 48201, USA
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Jusoh AR, Mohan SV, Lu Ping T, Tengku Din TADAAB, Haron J, Romli RC, Jaafar H, Nafi SN, Tuan Salwani TI, Yahya MM. Plasma Circulating Mirnas Profiling for Identification of Potential Breast Cancer Early Detection Biomarkers. Asian Pac J Cancer Prev 2021; 22:1375-1381. [PMID: 34048164 PMCID: PMC8408402 DOI: 10.31557/apjcp.2021.22.5.1375] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 05/12/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE This study aimed to characterize the miRNA expression profiles from plasma samples of our local breast cancer patients in comparison to healthy control by using miRNA PCR Array. METHODS In this study, plasma miRNA profiles from eight early-stage breast cancer patients and nine age-matched (± 2 years) healthy controls were characterized by miRNA array-based approach, followed by differential gene expression analysis, Independent T-test and construction of Receiver Operating Characteristic (ROC) curve to determine the capability of the assays to discriminate between breast cancer and the healthy control. RESULTS Based on the 372-miRNAs microarray profiling, a set of 40 differential miRNAs was extracted regarding to the fold change value at 2 and above. We further sub grouped 40 miRNAs of breast cancer patients that were significantly expressed at 2-fold change and higher. In this set, we discovered that 24 miRNAs were significantly upregulated and 16 miRNAs were significantly downregulated in breast cancer patients, as compared to the miRNA expression of healthy subjects. ROC curve analysis revealed that seven miRNAs (miR-125b-5p, miR-142-3p, miR-145-5p, miR-193a-5p, miR-27b-3p, miR-22-5p and miR-423-5p) had area under curve (AUC) value > 0.7 (AUC p-value < 0.05). Overlapping findings from differential gene expression analysis, ROC analysis, and Independent T-Test resulted in three miRNAs (miR-27b-3p, miR-22-5p, miR-145-5p). Cohen's effect size for these three miRNAs was large with d value are more than 0.95. CONCLUSION miR-27b-3p, miR-22-5p, miR-145-5p could be potential biomarkers to distinguish breast cancer patients from healthy controls. A validation study for these three miRNAs in an external set of samples is ongoing.
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Affiliation(s)
- A. Rashid Jusoh
- Department of Biomedicine, School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
| | - Sivanesan Vijaya Mohan
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health, Kuala Lumpur, Malaysia.
| | - Tan Lu Ping
- Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Ministry of Health, Kuala Lumpur, Malaysia.
| | | | - Juhara Haron
- Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
| | - Roslini Che Romli
- Breast Cancer Awareness and Research Unit, Hospital Universiti Sains Malaysia, Kelantan, Malaysia.
| | - Hasnan Jaafar
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
| | - Siti Norasikin Nafi
- Breast Cancer Awareness and Research Unit, Hospital Universiti Sains Malaysia, Kelantan, Malaysia.
| | - Tuan Ismail Tuan Salwani
- Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
| | - Maya Mazuwin Yahya
- Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
- Department of Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
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Matboli M, Hasanin AH, Hussein R, El-Nakeep S, Habib EK, Ellackany R, Saleh LA. Cyanidin 3-glucoside modulated cell cycle progression in liver precancerous lesion, in vivo study. World J Gastroenterol 2021; 27:1435-1450. [PMID: 33911466 PMCID: PMC8047539 DOI: 10.3748/wjg.v27.i14.1435] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/22/2021] [Accepted: 03/26/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cyanidin-3-O-glucoside (cyan) exhibits antioxidant and anticancer properties. The cell cycle proteins and antimitotic drugs might be promising therapeutic targets in hepatocellular carcinoma. AIM To investigate the effect of cyan administration on cell cycle in hepatic precancerous lesion (PCL) induced by diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) in Wistar rats. METHODS In vivo, DEN/2-AAF-induced hepatic PCL, rats were treated with three doses of cyan (10, 15, and 20 mg/kg/d, for four consecutive days per week for 16 wk). Blood and liver tissue samples were collected for measurement of the followings; alpha fetoprotein (AFP) liver function and RNA panel differential expression was evaluated via real time polymerase chain reaction. Histopathological examination of liver sections stained with H&E and immunohistochemical study using glutathione S-transferase placental (GSTP) and proliferating cell nuclear antigen (PCNA) antibodies were assessed. RESULTS Cyan administration mitigated the effect of DEN/2-AFF induced PCL, decreased AFP levels, and improved liver function. Remarkably, treatment with cyan dose dependently decreased the long non-coding RNA MALAT1 and tubulin gamma 1 mRNA expressions and increased the levels of miR-125b, all of which are involved in cell cycle and mitotic spindle assembly. Of note, cyan decreased GSTP foci percent area and PCNA positively stained nuclei. CONCLUSION Our results indicated that cyan could be used as a potential therapeutic agent to inhibit liver carcinogenesis in rat model via modulation of cell cycle.
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Affiliation(s)
- Marwa Matboli
- Department of Biochemistry, Ain Shams Faculty of Medicine, Cairo 11318, Egypt
| | - Amany H Hasanin
- Department of Clinical Pharmacology, Ain Shams Faculty of Medicine, Cairo 11381, Egypt
| | - Reham Hussein
- Department of Clinical Pharmacology, Ain Shams Faculty of Medicine, Cairo 11381, Egypt
| | - Sarah El-Nakeep
- Department of General Internal Medicine, Ain Shams Faculty of Medicine, Cairo 11381, Egypt
| | - Eman K Habib
- Department of Anatomy & Embryology, Ain Shams Faculty of Medicine, Cairo 11318, Egypt
| | - Rawan Ellackany
- Department of Undergraduate, Faculty of Medicine, Modern University for Technology and Information, Cairo 11381, Egypt
| | - Lobna A Saleh
- Department of Clinical Pharmacology, Ain Shams Faculty of Medicine, Cairo 11381, Egypt
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Hunt PJ, Kabotyanski KE, Calin GA, Xie T, Myers JN, Amit M. Interrupting Neuron-Tumor Interactions to Overcome Treatment Resistance. Cancers (Basel) 2020; 12:E3741. [PMID: 33322770 PMCID: PMC7762969 DOI: 10.3390/cancers12123741] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/04/2020] [Accepted: 12/04/2020] [Indexed: 12/19/2022] Open
Abstract
Neurons in the tumor microenvironment release neurotransmitters, neuroligins, chemokines, soluble growth factors, and membrane-bound growth factors that solid tumors leverage to drive their own survival and spread. Tumors express nerve-specific growth factors and microRNAs that support local neurons and guide neuronal growth into tumors. The development of feed-forward relationships between tumors and neurons allows tumors to use the perineural space as a sanctuary from therapy. Tumor denervation slows tumor growth in animal models, demonstrating the innervation dependence of growing tumors. Further in vitro and in vivo experiments have identified many of the secreted signaling molecules (e.g., acetylcholine, nerve growth factor) that are passed between neurons and cancer cells, as well as the major signaling pathways (e.g., MAPK/EGFR) involved in these trophic interactions. The molecules involved in these signaling pathways serve as potential biomarkers of disease. Additionally, new treatment strategies focus on using small molecules, receptor agonists, nerve-specific toxins, and surgical interventions to target tumors, neurons, and immune cells of the tumor microenvironment, thereby severing the interactions between tumors and surrounding neurons. This article discusses the mechanisms underlying the trophic relationships formed between neurons and tumors and explores the emerging therapies stemming from this work.
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Affiliation(s)
- Patrick J. Hunt
- Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; (P.J.H.); (K.E.K.)
- Department of Neurosurgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA
| | - Katherine E. Kabotyanski
- Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; (P.J.H.); (K.E.K.)
| | - George A. Calin
- Translational Molecular Pathology, Division of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Tongxin Xie
- Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA; (T.X.); (J.N.M.)
| | - Jeffrey N. Myers
- Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA; (T.X.); (J.N.M.)
| | - Moran Amit
- Department of Head and Neck Surgery, Division of Surgery, MD Anderson Cancer Center, Houston, TX 77030, USA; (T.X.); (J.N.M.)
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Attari F, Keighobadi F, Abdollahi M, Arefian E, Lotfizadeh R, Sepehri H, Moridi Farimani M. Inhibitory effect of flavonoid xanthomicrol on triple-negative breast tumor via regulation of cancer-associated microRNAs. Phytother Res 2020; 35:1967-1982. [PMID: 33217075 DOI: 10.1002/ptr.6940] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 09/12/2020] [Accepted: 10/17/2020] [Indexed: 12/13/2022]
Abstract
Breast cancer is the leading cause of cancer death in women worldwide. Due to the side effects of current chemo-reagents on healthy tissues, it is essential to search for alternative compounds with less toxicity and better efficacy. In the present study, we have investigated the anticancer effects of flavonoid xanthomicrol on the mice breast cancer model using MTT assay, cell cycle and Annexin/PI analysis, colony formation assay, H&E staining, immunohistochemistry, and miRNA analysis. Our results demonstrated that xanthomicrol decreased the cell viability and clonogenic capability, induced G1-arrest and apoptosis in the breast cancer cells in vitro, and caused a significant reduction in the volume and weight of mice tumors in vivo. In addition, xanthomicrol reduced the expression of TNFα, VEGF, MMP9, and Ki67, while upregulating the expression of apoptotic markers such as Bax, caspase3, and caspase9. Finally, the expression of miR21, miR27, and miR125, known as oncomirs, decreased significantly after xanthomicrol administration, while the expression of miR29 and miR34, functioning as tumor suppressors, increased significantly (p < .001). Our data demonstrated that xanthomicrol can induce apoptosis and suppress angiogenesis in breast cancer cells due to its inhibitory effect on oncomirs and its stimulatory effect on tumor suppressor miRNAs.
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Affiliation(s)
- Farnoosh Attari
- Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Faezeh Keighobadi
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), and Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Ehsan Arefian
- Molecular Virology Lab, Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Reza Lotfizadeh
- Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Houri Sepehri
- Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Mahdi Moridi Farimani
- Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran
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Gupta M, Chandan K, Sarwat M. Role of microRNA and Long Non-Coding RNA in Hepatocellular Carcinoma. Curr Pharm Des 2020; 26:415-428. [PMID: 31939724 PMCID: PMC7403690 DOI: 10.2174/1381612826666200115093835] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 12/04/2019] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) accounts for about 80-90% of all liver cancers and is found to be the third most common cause of cancer mortality in the Asia-Pacific region. Risk factors include hepatitis B and C virus, cirrhosis, aflatoxin-contaminated food, alcohol, and diabetes. Surgically removing the tumor tissue seems effective but a high chance of recurrence has led to an urgent need to develop novel molecules for the treatment of HCC. Clinical management with sorafenib is found to be effective but it is only able to prolong survival for a few months. Various side effects like gastrointestinal and abdominal pain, hypertension, and hemorrhage are also associated with sorafenib, which calls for the unmet need of effective therapies against HCC. Similarly, the genetic mechanisms behind the occurrence of HCC are still unknown and need to be expounded further for developing newer candidates. Since unearthing the concept of these variants, transcriptomics has revealed the role of non-coding RNAs (ncRNAs) in many cellular, physiological and pathobiological processes. They are also found to be widely associated and abundantly expressed in a variety of cancer. Aberrant expression and mutations are closely related to tumorigenesis and metastasis and hence are classified as novel biomarkers and therapeutic targets for the treatment of cancer, including HCC. Herein, this review summarises the relationship between ncRNAs and hepatocellular carcinoma.
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Affiliation(s)
- Meenakshi Gupta
- Amity Institute of Pharmacy, Amity University, Noida-201313, Uttar Pradesh, India
| | - Kumari Chandan
- Amity Institute of Pharmacy, Amity University, Noida-201313, Uttar Pradesh, India
| | - Maryam Sarwat
- Amity Institute of Pharmacy, Amity University, Noida-201313, Uttar Pradesh, India
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Feliciano A, González L, Garcia-Mayea Y, Mir C, Artola M, Barragán N, Martín R, Altés A, Castellvi J, Benavente S, Ramón Y Cajal S, Espinosa-Bravo M, Cortés J, Rubio IT, LLeonart ME. Five microRNAs in Serum Are Able to Differentiate Breast Cancer Patients From Healthy Individuals. Front Oncol 2020; 10:586268. [PMID: 33224883 PMCID: PMC7670964 DOI: 10.3389/fonc.2020.586268] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 09/17/2020] [Indexed: 01/15/2023] Open
Abstract
Breast cancer is the cancer with the most incidence and mortality in women. microRNAs are emerging as novel prognosis/diagnostic tools. Our aim was to identify a serum microRNA signature useful to predict cancer development. We focused on studying the expression levels of 30 microRNAs in the serum of 96 breast cancer patients vs. 92 control individuals. Bioinformatic studies provide a microRNA signature, designated as a predictor, based on the expression levels of five microRNAs. Then, we tested the predictor in a group of 60 randomly chosen women. Lastly, a proteomic study unveiled the overexpression and downregulation of proteins differently expressed in the serum of breast cancer patients vs. that of control individuals. Twenty-six microRNAs differentiate cancer tissue from healthy tissue, and 16 microRNAs differentiate the serum of cancer patients from that of the control group. The tissue expression of miR-99a, miR-497, miR-362, and miR-1274, and the serum levels of miR-141 correlated with patient survival. Moreover, the predictor consisting of miR-125b, miR-29c, miR-16, miR-1260, and miR-451 was able to differentiate breast cancer patients from controls. The predictor was validated in 20 new cases of breast cancer patients and tested in 60 volunteer women, assigning 11 out of 60 women to the cancer group. An association of low levels of miR-16 with a high content of CD44 protein in serum was found. Circulating microRNAs in serum can represent biomarkers for cancer prediction. Their clinical relevance and the potential use of the predictor here described are discussed.
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Affiliation(s)
- Andrea Feliciano
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Lucila González
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Yoelsis Garcia-Mayea
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Cristina Mir
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mireia Artola
- Primary Care Center CAP-Vallcarca-Sant Gervasi, Barcelona, Spain
| | - Nieves Barragán
- Primary Care Center CAP-Vallcarca-Sant Gervasi, Barcelona, Spain
| | - Remedios Martín
- Primary Care Center CAP-Vallcarca-Sant Gervasi, Barcelona, Spain
| | - Anna Altés
- Primary Care Center CAP-Vallcarca-Sant Gervasi, Barcelona, Spain
| | - Josep Castellvi
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Sergi Benavente
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Santiago Ramón Y Cajal
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Javier Cortés
- Institute of Breast Cancer, Quiron Group, Barcelona, Spain.,Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Isabel T Rubio
- Breast Surgical Oncology, University of Navarra Clinic, Madrid, Spain
| | - Matilde E LLeonart
- Biomedical Research in Cancer Stem Cells Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.,Spanish Biomedical Research Network Center in Oncology, Madrid, Spain
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Lv J, An J, Zhang YD, Li ZX, Zhao GL, Gao J, Hu WW, Chen HM, Li AM, Jiang QS. A three serum miRNA panel as diagnostic biomarkers of radiotherapy-related metastasis in non-small cell lung cancer. Oncol Lett 2020; 20:236. [PMID: 32968458 PMCID: PMC7500041 DOI: 10.3892/ol.2020.12099] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 07/23/2020] [Indexed: 12/11/2022] Open
Abstract
Serum microRNAs (miRNAs) have been implicated as noninvasive biomarkers for lung cancer diagnosis. However, there are no sensitive and specific biomarkers for the detection of radiotherapy-related non-small cell lung cancer (NSCLC) metastasis. The present study aimed to investigate the role of three serum miRNAs, namely miRNA (miR)-130a, miR-25 and miR-191*, in diagnosing NSCLC, and their biological functions in radiation-mediated development of metastatic properties in A549 cells. To determine this, serum samples were collected from 84 patients with NSCLC and 42 age- and sex-matched healthy controls. Differential expression of serum miRNAs was analyzed by quantitative PCR. Significant associations between miRNA expression and overall survival of patients with NSCLC were identified using the Cox proportional regression model. A receiver operating characteristic curve was generated to evaluate diagnostic accuracy. The functions of miR-130a, miR-25 and miR-191* in lung cancer cells were studied by transfecting A549 cells with miRNA mimics and inhibitors. The results of the present study demonstrated that the expression levels of miR-130a, miR-25 and miR-191* in the serum of patients with NSCLC were increased compared with those in healthy controls, and these increases were associated with advanced age (≥60 years), radiotherapy, histological type (squamous carcinoma), low survival rate and low median survival time. Additionally, irradiation induced the upregulation of miR-130a, miR-25 and miR-191* expression in A549 cells in vitro and in a xenograft mouse model. Irradiation also promoted the invasiveness of A549 cells in vitro and metastasis in vivo. In conclusion, miR-130a, miR-25 and miR-191* may be potential biomarkers for the diagnosis of patients with NSCLC and may serve oncogenic roles in radiation-mediated metastasis of NSCLC.
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Affiliation(s)
- Jin Lv
- Research Department, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Juan An
- Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Yang-Dong Zhang
- Research Department, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Zhao-Xia Li
- Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Guang-Li Zhao
- Health Management Division, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Jun Gao
- Research Department, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Wen-Wei Hu
- Department of Endoscopy, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Huo-Ming Chen
- Department of Oncology, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
| | - Ai-Min Li
- Research Department, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China.,Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, P.R. China
| | - Qi-Sheng Jiang
- Research Department, PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China
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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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Zhao P, Cui X, Zhao L, Liu L, Wang D. Overexpression of Growth-Arrest-Specific Transcript 5 Improved Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222. DNA Cell Biol 2020; 39:724-732. [PMID: 32213078 DOI: 10.1089/dna.2019.5282] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Long noncoding RNA growth-arrest-specific transcript 5 (GAS5) has been proved to play a crucial role in cancer chemoresistance. However, the function of GAS5 and its underlying molecular mechanism in hepatocellular carcinoma (HCC) chemoresistance remain unknown. In this study, we aimed to investigate its function and underlying molecular mechanism in HCC cisplatin (CDDP) resistance. The results demonstrated that GAS5 was significantly downregulated in HCC tissues and cells, especially in CDDP-resistant HCC tissues and cells. Low GAS5 expression was tightly correlated with shorter survival in patients with HCC. Functionally, GAS5 overexpression sensitized CDDP-resistant HepG2/CDDP and Huh7/CDDP cells to CDDP. Mechanically, GAS5 improved the sensitivity of HCC cells to CDDP through sponging miR-222. Taken together, these observations suggested that overexpression of GAS5 overcame CDDP resistance of HCC cells by regulating miR-222, providing a potential therapeutic target for overcoming the chemoresistance of HCC cells.
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Affiliation(s)
- Panxiong Zhao
- Department of Nuclear Medicine, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Xi Cui
- Department of Endocrinology, Huaihe Hospital of Henan University, Kaifeng, China
| | - Liyan Zhao
- Department of Breast Thyroid Surgery, Huaihe Hospital of Henan University, Kaifeng, China
| | - Lu Liu
- Department of Respiratory Medicine, Huaihe Hospital of Henan University, Kaifeng, China
| | - Dayong Wang
- Department of Nuclear Medicine, The First Affiliated Hospital of Henan University, Kaifeng, China
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Zhang Z, Li W, Jiang D, Liu C, Lai Z. MicroRNA-139-5p inhibits cell viability, migration and invasion and suppresses tumor growth by targeting HDGF in non-small cell lung cancer. Oncol Lett 2020; 19:1806-1814. [PMID: 32194674 PMCID: PMC7039177 DOI: 10.3892/ol.2020.11296] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 07/10/2019] [Indexed: 12/13/2022] Open
Abstract
MicroRNA (miRNAs) serve key roles in the progress of various types of cancer. The expression of miRNA (miR)-139-5p is downregulated in several types of tumor and has been recognized as a tumor suppressor. However, the role of miR-139-5p in non-small cell lung cancer (NSCLC) has not been investigated in detail. In the present study, it was demonstrated that miR-139-5p was significantly downregulated in NSCLC cells and tissues, and the overexpression of miR-139-5p in vitro induced apoptosis and significantly inhibited the viability and proliferation of A549 and H1299 cells. In addition, upregulation of miR-139-5p significantly inhibited the migration and invasion of A549 and H1299 cells. Hepatoma-derived growth factor (HDGF) was identified as a direct target of miR-139-5p. Rescue experiments demonstrated that the inhibitory function of miR-139-5p on cell viability, migration and invasion was partially mediated by suppressing HDGF expression. Furthermore, miR-139-5p exhibited efficient inhibition of tumor growth in a xenograft tumor mouse model of A549 cells. In summary, the results from the present study suggested that miR-139-5p may serve an important role in NSCLC by targeting HDGF and causing inhibition of cell viability and metastasis, as well as induction of apoptosis. miR-139-5p may also have the potential to serve as a therapeutic target for the treatment of NSCLC.
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Affiliation(s)
- Zuxiong Zhang
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
| | - Weizhi Li
- Department of Radiotherapy, Tumor Hospital of Ganzhou, Ganzhou, Jiangxi 341000, P.R. China
| | - Damei Jiang
- Department of Obstetrics and Gynecology, Ganzhou Municipal Hospital, Ganzhou, Jiangxi 341000, P.R. China
| | - Chi Liu
- School of Medical and Life Sciences, Chengdu University of TCM, Chengdu, Sichuan 610072, P.R. China
| | - Zhenghong Lai
- Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
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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: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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49
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Matuszyk J, Klopotowska D. miR‐125b lowers sensitivity to apoptosis following mitotic arrest: Implications for breast cancer therapy. J Cell Physiol 2020; 235:6335-6344. [DOI: 10.1002/jcp.29610] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 01/22/2020] [Indexed: 01/10/2023]
Affiliation(s)
- Janusz Matuszyk
- Hirszfeld Institute of Immunology and Experimental TherapyPolish Academy of Sciences 12 R. Weigla Street 53‐114 Wroclaw Poland
| | - Dagmara Klopotowska
- Hirszfeld Institute of Immunology and Experimental TherapyPolish Academy of Sciences 12 R. Weigla Street 53‐114 Wroclaw Poland
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Kashyap D, Kaur H. Cell-free miRNAs as non-invasive biomarkers in breast cancer: Significance in early diagnosis and metastasis prediction. Life Sci 2020; 246:117417. [PMID: 32044304 DOI: 10.1016/j.lfs.2020.117417] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/28/2020] [Accepted: 02/05/2020] [Indexed: 02/07/2023]
Abstract
Breast cancer is one of the genetic diseases causing a high mortality among women around the world. Despite the availability of advanced diagnostic tools and treatment strategies, the incidence of breast cancer is increasing every year. This is due to the lack of accurate and reliable biomarkers whose deficiency creates difficulty in early breast cancer recognition, subtypes determination, and metastasis prophecy. Although biomarkers such as ER, PR, Her2, Ki-67, and other genetic platforms e.g. MammaPrint®, Oncotype DX®, Prosigna® or EndoPredict® are available for determination of breast cancer diagnosis and prognosis. However, pertaining to heterogeneous nature, lack of sensitivity, and specificity of these markers, it is still incessant to overcome breast cancer burden. Therefore, a novel biomarker is urgently needed for therapeutic diagnosis and improving prognosis. Lately, it has become more evident that cell-free miRNAs might be useful as good non-invasive biomarkers that are associated with different events in carcinogenesis. For example, some known biomarkers such as miR-21, miR-23a, miR-34a are associated with molecular subtyping and different biomolecular aspects i.e. apoptosis, angiogenesis, metastasis, and miR-1, miR-10b, miR-16 are associated with drug response. Cell-free miRNAs present in human body fluids have proven to be potential biomarkers with significant prognostic and predictive values. Numerous studies have found a distinct expression profile of circulating miRNAs in breast tumour versus non-tumour and in early and advanced-stage, thus implicating its clinical relevance. This review article will highlight the importance of different cell-free miRNAs as a biomarker for early breast cancer detection, subtype classification, and metastasis forecast.
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Affiliation(s)
- Dharambir Kashyap
- Department of Histopathology, Postgraduation Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Harmandeep Kaur
- Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
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