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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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Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
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Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
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3
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Ling H, Wang XC, Liu ZY, Mao S, Yang JJ, Sha JM, Tao H. Noncoding RNA network crosstalk in organ fibrosis. Cell Signal 2024; 124:111430. [PMID: 39312989 DOI: 10.1016/j.cellsig.2024.111430] [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: 07/24/2024] [Revised: 09/12/2024] [Accepted: 09/19/2024] [Indexed: 09/25/2024]
Abstract
Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.
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Affiliation(s)
- Hui Ling
- Department of Thoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Xian-Chen Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Zhi-Yan Liu
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Sui Mao
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
| | - Jing-Jing Yang
- Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
| | - Ji-Ming Sha
- Department of Thoracic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
| | - Hui Tao
- Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
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4
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Pu J, Yan X, Zhang H. The potential of circular RNAs as biomarkers and therapeutic targets for gastric cancer: A comprehensive review. J Adv Res 2024:S2090-1232(24)00551-4. [PMID: 39617262 DOI: 10.1016/j.jare.2024.11.032] [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: 07/11/2024] [Revised: 11/22/2024] [Accepted: 11/26/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Gastric cancer (GC) is a global health concern, contributing significantly to cancer-related mortality rates. Early detection is vital for improving patient outcomes. Recently, circular RNAs (circRNAs) have emerged as crucial players in the development and progression of various cancers, including GC. AIM This comprehensive review underscores the promising potential of circRNAs as innovative biomarkers for the early diagnosis of GC, as well as their possible utility as therapeutic targets for this life-threatening disease. Specifically, the review focuses on recent findings, mechanistic insights, and clinical applications of circRNAs in GC. KEY SCIENTIFIC CONCEPTS OF REVIEW Dysregulation of circRNAs has been consistently observed in GC tissues, offering potential diagnostic value due to their stability in bodily fluids such as blood and urine. For instance, circPTPN22 and hsa_circ_000200. Furthermore, the expression levels of circRNAs such as circCUL2, hsa_circ_0000705 and circSHKBP1 have shown strong associations with critical clinical features of GC, including diagnosis, prognosis, tumor size, lymph node metastasis, tumor-node-metastasis (TNM) stage, and treatment response. Additionally, circRNAs such as circBGN, circLMO7, and circMAP7D1 have shown interactions with specific microRNAs (miRNAs), proteins, and other molecules that play key roles in development and progression of GC. This further highlighting their potential as therapeutic targets. Despite their potential, several challenges need to be addressed to effectively apply circRNAs as GC biomarkers. These include standardizing detection methods, establishing cutoff values for diagnostic accuracy, and validating findings in larger patient cohorts. Moreover, the functional mechanisms by which circRNAs contribute to GC pathogenesis and therapeutic resistance warrant further investigation. Advances in circRNAs research could provide valuable insights into the early detection and targeted treatment of GC, ultimately improving patient outcomes.
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Affiliation(s)
- Junlin Pu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiuli Yan
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
| | - Hui Zhang
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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5
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Hama Faraj GS, Hussen BM, Abdullah SR, Fatih Rasul M, Hajiesmaeili Y, Baniahmad A, Taheri M. Advanced approaches of the use of circRNAs as a replacement for cancer therapy. Noncoding RNA Res 2024; 9:811-830. [PMID: 38590433 PMCID: PMC10999493 DOI: 10.1016/j.ncrna.2024.03.012] [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: 12/14/2023] [Revised: 03/18/2024] [Accepted: 03/29/2024] [Indexed: 04/10/2024] Open
Abstract
Cancer is a broad name for a group of diseases in which abnormal cells grow out of control and are characterized by their complexity and recurrence. Although there has been progress in cancer therapy with the entry of precision medicine and immunotherapy, cancer incidence rates have increased globally. Non-coding RNAs in the form of circular RNAs (circRNAs) play crucial roles in the pathogenesis, clinical diagnosis, and therapy of different diseases, including cancer. According to recent studies, circRNAs appear to serve as accurate indicators and therapeutic targets for cancer treatment. However, circRNAs are promising candidates for cutting-edge cancer therapy because of their distinctive circular structure, stability, and wide range of capabilities; many challenges persist that decrease the applications of circRNA-based cancer therapeutics. Here, we explore the roles of circRNAs as a replacement for cancer therapy, highlight the main challenges facing circRNA-based cancer therapies, and discuss the key strategies to overcome these challenges to improve advanced innovative therapies based on circRNAs with long-term health effects.
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Affiliation(s)
- Goran Sedeeq Hama Faraj
- Department of Medical Laboratory Science, Komar University of Science and Technology, Sulaymaniyah, 46001, Iraq
| | - Bashdar Mahmud Hussen
- Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Erbil, Kurdistan Region, 44001, Iraq
- Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan Region, 44001, Iraq
| | - Snur Rasool Abdullah
- Medical Laboratory Science, Lebanese French University, Erbil, Kurdistan Region, 44001, Iraq
| | - Mohammed Fatih Rasul
- Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan Region, Iraq
| | | | - Aria Baniahmad
- Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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6
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Zhang J, Luo Z, Zheng Y, Duan M, Qiu Z, Huang C. CircRNA as an Achilles heel of cancer: characterization, biomarker and therapeutic modalities. J Transl Med 2024; 22:752. [PMID: 39127679 DOI: 10.1186/s12967-024-05562-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs characterized by their lack of 5' caps and 3' poly(A) tails. These molecules have garnered substantial attention from the scientific community. A wide range of circRNA types has been found to be expressed in various tissues of the human body, exhibiting unique characteristics such as high abundance, remarkable stability, and tissue-specific expression patterns. These attributes, along with their detectability in liquid biopsy samples such as plasma, position circRNAs an ideal choice as cancer diagnostic and prognostic biomarkers. Additionally, several studies have reported that the functions of circRNAs are associated with tumor proliferation, metastasis, and drug resistance. They achieve this through various mechanisms, including modulation of parental gene expression, regulation of gene transcription, acting as microRNA (miRNA) sponges, and encoding functional proteins. In recent years, a large number of studies have focused on synthesizing circRNAs in vitro and delivering them to tumor tissue to exert its effects in inhibit tumor progression. Herein, we briefly discuss the biogenesis, characteristics, functions, and detection of circRNAs, emphasizing their clinical potential as biomarkers for cancer diagnosis and prognosis. We also provide an overview the recent techniques for synthesizing circRNAs and delivery strategies, and outline the application of engineered circRNAs in clinical cancer therapy.
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Affiliation(s)
- Jun Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China
| | - Zai Luo
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China.
| | - Yang Zheng
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China
| | - Mingyu Duan
- Department of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 650 Xinsongjiang Road, Songjiang District, Shanghai, 201600, China
| | - Zhengjun Qiu
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, China.
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7
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Yin W, Wang S, Qiao S, Zhao Y, Wu W, Pang S, Lv Z. DETHACDA: A Dual-View Edge and Topology Hybrid Attention Model for CircRNA-Disease Associations Prediction. IEEE J Biomed Health Inform 2024; 28:4421-4431. [PMID: 37307176 DOI: 10.1109/jbhi.2023.3284851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
There exists growing evidence that circRNAs are concerned with many complex diseases physiological processes and pathogenesis and may serve as critical therapeutic targets. Identifying disease-associated circRNAs through biological experiments is time-consuming, and designing an intelligent, precise calculation model is essential. Recently, many models based on graph technology have been proposed to predict circRNA-disease association. However, most existing methods only capture the neighborhood topology of the association network and ignore the complex semantic information. Therefore, we propose a Dual-view Edge and Topology Hybrid Attention model for predicting CircRNA-Disease Associations (DETHACDA), effectively capturing the neighborhood topology and various semantics of circRNA and disease nodes in a heterogeneous network. The 5-fold cross-validation experiments on circRNADisease indicate that the proposed DETHACDA achieves the area under receiver operating characteristic curve of 0.9882, better than four state-of-the-art calculation methods.
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8
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Kohansal M, Alghanimi YK, Banoon SR, Ghasemian A, Afkhami H, Daraei A, Wang Z, Nekouian N, Xie J, Deng X, Tang H. CircRNA-associated ceRNA regulatory networks as emerging mechanisms governing the development and biophysiopathology of epilepsy. CNS Neurosci Ther 2024; 30:e14735. [PMID: 38676299 PMCID: PMC11053249 DOI: 10.1111/cns.14735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 03/17/2024] [Accepted: 04/07/2024] [Indexed: 04/28/2024] Open
Abstract
The etiology of epilepsy is ascribed to the synchronized aberrant neuronal activity within the brain. Circular RNAs (circRNAs), a class of non-coding RNAs characterized by their circular structures and covalent linkage, exert a substantial influence on this phenomenon. CircRNAs possess stereotyped replication, transience, repetitiveness, and paroxysm. Additionally, MicroRNA (miRNA) plays a crucial role in the regulation of diverse pathological processes, including epilepsy. CircRNA is of particular significance due to its ability to function as a competing endogenous RNA, thereby sequestering or inhibiting miRNA activity through binding to target mRNA. Our review primarily concentrates on elucidating the pathological and functional roles, as well as the underlying mechanisms, of circRNA-miRNA-mRNA networks in epilepsy. Additionally, it explores the potential utility of these networks for early detection and therapeutic intervention.
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Affiliation(s)
- Maryam Kohansal
- Noncommunicable Diseases Research CenterFasa University of Medical SciencesFasaIran
- Department of BiologyPayame Noor UniversityTehranIran
| | | | - Shaimaa R. Banoon
- Department of Biology, College of ScienceUniversity of MisanAmarahIraq
| | - Abdolmajid Ghasemian
- Noncommunicable Diseases Research CenterFasa University of Medical SciencesFasaIran
| | - Hamed Afkhami
- Nervous System Stem Cells Research CenterSemnan University of Medical SciencesSemnanIran
- Cellular and Molecular Research CenterQom University of Medical SciencesQomIran
- Faculty of MedicineShahed UniversityTehranIran
| | - Abdolreza Daraei
- Cellular and Molecular Biology Research Center, Health Research InstituteBabol University of Medical SciencesBabolIran
| | - Zhangling Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouChina
| | - Najmeh Nekouian
- Noncommunicable Diseases Research CenterFasa University of Medical SciencesFasaIran
| | - Jindong Xie
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouChina
| | - Xinpei Deng
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouChina
| | - Hailin Tang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouChina
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9
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Han HS, Lee KW. Liquid Biopsy: An Emerging Diagnostic, Prognostic, and Predictive Tool in Gastric Cancer. J Gastric Cancer 2024; 24:4-28. [PMID: 38225764 PMCID: PMC10774753 DOI: 10.5230/jgc.2024.24.e5] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 12/05/2023] [Accepted: 12/06/2023] [Indexed: 01/17/2024] Open
Abstract
Liquid biopsy, a minimally invasive procedure that causes minimal pain and complication risks to patients, has been extensively studied for cancer diagnosis and treatment. Moreover, it facilitates comprehensive quantification and serial assessment of the whole-body tumor burden. Several biosources obtained through liquid biopsy have been studied as important biomarkers for establishing early diagnosis, monitoring minimal residual disease, and predicting the prognosis and response to treatment in patients with cancer. Although the clinical application of liquid biopsy in gastric cancer is not as robust as that in other cancers, biomarker studies using liquid biopsy are being actively conducted in patients with gastric cancer. Herein, we aimed to review the role of various biosources that can be obtained from patients with gastric cancer through liquid biopsies, such as blood, saliva, gastric juice, urine, stool, peritoneal lavage fluid, and ascites, by dividing them into cellular and acellular components. In addition, we reviewed previous studies on the diagnostic, prognostic, and predictive biomarkers for gastric cancer using liquid biopsy and discussed the limitations of liquid biopsy and the challenges to overcome these limitations in patients with gastric cancer.
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Affiliation(s)
- Hye Sook Han
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
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10
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Li J, Xu S, Zhu F, Shen F, Zhang T, Wan X, Gong S, Liang G, Zhou Y. Multi-omics Combined with Machine Learning Facilitating the Diagnosis of Gastric Cancer. Curr Med Chem 2024; 31:6692-6712. [PMID: 38351697 DOI: 10.2174/0109298673284520240112055108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/28/2023] [Accepted: 01/03/2024] [Indexed: 10/19/2024]
Abstract
Gastric cancer (GC) is a highly intricate gastrointestinal malignancy. Early detection of gastric cancer forms the cornerstone of precision medicine. Several studies have been conducted to investigate early biomarkers of gastric cancer using genomics, transcriptomics, proteomics, and metabolomics, respectively. However, endogenous substances associated with various omics are concurrently altered during gastric cancer development. Furthermore, environmental exposures and family history can also induce modifications in endogenous substances. Therefore, in this study, we primarily investigated alterations in DNA mutation, DNA methylation, mRNA, lncRNA, miRNA, circRNA, and protein, as well as glucose, amino acid, nucleotide, and lipid metabolism levels in the context of GC development, employing genomics, transcriptomics, proteomics, and metabolomics. Additionally, we elucidate the impact of exposure factors, including HP, EBV, nitrosamines, smoking, alcohol consumption, and family history, on diagnostic biomarkers of gastric cancer. Lastly, we provide a summary of the application of machine learning in integrating multi-omics data. Thus, this review aims to elucidate: i) the biomarkers of gastric cancer related to genomics, transcriptomics, proteomics, and metabolomics; ii) the influence of environmental exposure and family history on multiomics data; iii) the integrated analysis of multi-omics data using machine learning techniques.
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Affiliation(s)
- Jie Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Siyi Xu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Feng Zhu
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
| | - Fei Shen
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
| | - Tianyi Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xin Wan
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Saisai Gong
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Geyu Liang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Yonglin Zhou
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
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11
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Chen D, Shi L, Zhong D, Nie Y, Yang Y, Liu D. Hsa_circ_0002019 promotes cell proliferation, migration, and invasion by regulating TNFAIP6/NF-κB signaling in gastric cancer. Genomics 2023; 115:110641. [PMID: 37201873 DOI: 10.1016/j.ygeno.2023.110641] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 04/25/2023] [Accepted: 05/14/2023] [Indexed: 05/20/2023]
Abstract
BACKGROUND Gastric cancer (GC) is a common cancer with a high incidence and mortality rate. Herein, the role of hsa_circ_0002019 (circ_0002019) in GC was investigated. METHODS The molecular structure and stability of circ_0002019 were identified by RNase R, and Actinomycin D treatment. Molecular associations were verified by RIP. Proliferation, migration, and invasion were detected by CCK-8, EdU, and Transwell, respectively. The effect of circ_0002019 on tumor growth was analyzed in vivo. RESULTS Circ_0002019 was elevated in GC tissues and cells. Circ_0002019 knockdown inhibited the proliferation, migration, and invasion. Mechanically, circ_0002019 activated NF-κB signaling by increasing TNFAIP6 mRNA stability by PTBP1. Activation of NF-κB signaling limited the antitumor effect of circ_0002019 silencing in GC. Circ_0002019 knockdown inhibited tumor growth in vivo by reducing TNFAIP6 expression. CONCLUSIONS Circ_0002019 accelerated the proliferation, migration, and invasion by regulating TNFAIP6/NF-κB pathway, suggesting circ_0002019 could be a key regulatory factor in GC progression.
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Affiliation(s)
- Dan Chen
- Department of Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China
| | - Li Shi
- Department of Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China
| | - Dingfu Zhong
- Department of Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China
| | - Ying Nie
- Department of Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China
| | - Yi Yang
- Department of Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China
| | - Dong Liu
- Department of Hepatobiliary and Pancreatic Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China.
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12
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Li J, Song Y, Cai H, Zhou B, Ma J. Roles of circRNA dysregulation in esophageal squamous cell carcinoma tumor microenvironment. Front Oncol 2023; 13:1153207. [PMID: 37384299 PMCID: PMC10299836 DOI: 10.3389/fonc.2023.1153207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 05/30/2023] [Indexed: 06/30/2023] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most prevalent histological esophageal cancer characterized by advanced diagnosis, metastasis, resistance to treatment, and frequent recurrence. In recent years, numerous human disorders such as ESCC, have been linked to abnormal expression of circular RNAs (circRNAs), suggesting that they are fundamental to the intricate system of gene regulation that governs ESCC formation. The tumor microenvironment (TME), referring to the area surrounding the tumor cells, is composed of multiple components, including stromal cells, immune cells, the vascular system, extracellular matrix (ECM), and numerous signaling molecules. In this review, we briefly described the biological purposes and mechanisms of aberrant circRNA expression in the TME of ESCC, including the immune microenvironment, angiogenesis, epithelial-to-mesenchymal transition, hypoxia, metabolism, and radiotherapy resistance. As in-depth research into the processes of circRNAs in the TME of ESCC continues, circRNAs are promising therapeutic targets or delivery systems for cancer therapy and diagnostic and prognostic indicators for ESCC.
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Affiliation(s)
- Jingyi Li
- Department of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yuxia Song
- Department of Reproductive Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Huihong Cai
- Department of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Bo Zhou
- Medical Research Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jun Ma
- Department of Clinical Laboratory, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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13
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Haque S, Bhushan Raman R, Salam M. Role of Biomarkers in Hepatocellular Carcinoma and Their Disease Progression. LIVER CANCER - GENESIS, PROGRESSION AND METASTASIS 2023. [DOI: 10.5772/intechopen.105856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the third leading and common lethal cancers worldwide. Early detection of tumorigenesis of hepatocellular carcinoma is through ultrasonography, computerized tomography (CT) scans, and magnetic resonance imaging (MRI) scans; however, these methods are not up to the mark, so a search for an efficient biomarker for early diagnosis and treatment of hepatocarcinogenesis is important. Proteomic and genomic approaches aid to develop new promising biomarkers for the diagnosis of HCC at the early stages. These biomarkers not only help in prognosis but also provide better therapeutic intervention against HCC. Among the different biomarker candidates, liquid biopsy [including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)] has recently emerged as a noninvasive detection technique for the characterization of circulating cells, providing a strong basis and early diagnosis for the individualized treatment of patients. This review provides the current understanding of HCC biomarkers that predict the risk of HCC recurrence.
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Hsa_circ_0000520 Promotes Non-Small Cell Lung Cancer Progression through the miR-1258/AKT3 Axis. JOURNAL OF ONCOLOGY 2022; 2022:3676685. [PMID: 36593867 PMCID: PMC9805391 DOI: 10.1155/2022/3676685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 10/09/2022] [Accepted: 11/05/2022] [Indexed: 12/25/2022]
Abstract
Background There are several previous studies suggesting that circular RNAs (circRNAs) are involved in tumorigenesis of non-small cell lung cancer (NSCLC). Nevertheless, the role of circRNA_0000520 (circ_0000520) in this disease has not yet been studied. Methods circ_0000520, microRNA (miR)-1258, and AKT serine/threonine kinase 3 (AKT3) mRNA expression levels were detected by qPCR. CCK-8, EdU, and Transwell assays were utilized to detect NSCLC cells' malignant biological behaviors. The targeted relationship between miR-1258 and AKT3 3'-UTR or circ_0000520 was verified through the dual-luciferase reporter gene assay. Western blotting was utilized to measure the AKT3 expression after circ_0000520 and miR-1258 were selectively regulated. Results circ_0000520 was upregulated in NSCLC. Highly expressed circ_0000520 is linked to the NSCLC patient's advanced TNM stage and lymph node metastasis. circ_0000520 overexpression facilitated NSCLC cell growth, migration, and invasion. miR-1258 was identified as the downstream target of circ_0000520. miR-1258 overexpression weakened the effect of circ_0000520 overexpression on NSCLC cells. miR-1258 targeted and inhibited AKT3. circ_0000520 positively regulated the AKT3 expression in NSCLC cells by sponging miR-1258. Conclusion circ_0000520 upregulates AKT3 by competitively binding with miR-1258 to facilitate NSCLC progression.
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15
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Xu CY, Zeng XX, Xu LF, Liu M, Zhang F. Circular RNAs as diagnostic biomarkers for gastric cancer: A comprehensive update from emerging functions to clinical significances. Front Genet 2022; 13:1037120. [PMID: 36386850 PMCID: PMC9650219 DOI: 10.3389/fgene.2022.1037120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/10/2022] [Indexed: 08/30/2023] Open
Abstract
The incidence and mortality of gastric cancer ranks as a fouth leading cause of cancer death worldwide, especially in East Asia. Due to the lack of specific early-stage symptoms, the majority of patients in most developing nations are diagnosed at an advanced stage. Therefore, it is urgent to find more sensitive and reliable biomarkers for gastric cancer screening and diagnosis. Circular RNAs (circRNAs), a novel type of RNAs with covalently closed loops, are becoming a latest hot spot in the field of. In recent years, a great deal of research has demonstrated that abnormal expression of circRNAs was associated with the development of gastric cancer, and suggested that circRNA might serve as a potential biomarker for gastric cancer diagnosis. In this review, we summarize the structural characteristics, formation mechanism and biological function of circRNAs, and elucidate research progress and existing problems in early screening of gastric cancer.
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Affiliation(s)
- Chun-Yi Xu
- Zhejiang Chinese Medical University, Hangzhou, China
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
| | - Xi-Xi Zeng
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
| | - Li-Feng Xu
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
| | - Ming Liu
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
- The Joint Innovation Center for Engineering in Medicine, Quzhou, China
- University of Electronic Science and Technology of China, Chengdu, China
| | - Feng Zhang
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
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16
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Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights. Int J Biol Macromol 2022; 220:973-984. [PMID: 35977596 DOI: 10.1016/j.ijbiomac.2022.08.085] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/19/2022] [Accepted: 08/11/2022] [Indexed: 02/07/2023]
Abstract
Tumor microenvironment (TME) is a crucial regulator of tumor progression and cells in the TME release a number of molecules that are responsible for anaplasticity, invasion, metastasis of tumor, establishing stem cell niches, up-regulation and down-regulation of various pathways in cancer cells, interfering with immune surveillance and immune escape. Moreover, they can serve as diagnostic markers, and determine effective therapies. Among them, CircRNAs have gained special attention due to their involvement in mutated pathways in cancers. By functioning as a molecular sponge for miRNAs, binding with proteins, and directing selective splicing. CircRNAs modify the immunological environment of cancers to promote their growth. Besides of critical role in tumor growth, circRNAs are emerging as potential candidates as biomarkers for diagnosis cancer therapy. Also, circRNAs vaccination even offers a novel approach to tumor immunotherapy. Over the recent years, studies are advocating that circRNAs have tissue specific tumor specific expression patterns, which indicates their potential clinical utility. Especially, circRNAs have emerged as potential predictive and prognostic biomarkers. Although, there has been significant progress in deciphering the role of circRNA in cancers, literature lacks comprehensive overview on this topic. Keeping in view of these significant discoveries, this review systematically discusses circRNA and their role in the tumor in different dimensions.
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17
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Kan B, Yan G, Shao Y, Zhang Z, Xue H. CircRNA RNF10 inhibits tumorigenicity by targeting miR-942-5p/GOLIM4 axis in breast cancer. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2022; 63:362-372. [PMID: 36054164 DOI: 10.1002/em.22506] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/04/2022] [Accepted: 08/28/2022] [Indexed: 05/12/2023]
Abstract
We aimed to explore the action of a circRNA produced by ring finger protein 10 (circ_RNF10; hsa_circ_0028899) in the malignant behaviors of breast cancer (BC) and to explore its potential action-of-mechanism. The levels of circ_RNF10, miR-942-5p and Golgi integral membrane protein 4 (GOLIM4) were measured through quantitative real-time polymerase chain reaction, western blot, or immunohistochemistry, and the competing endogenous RNA (ceRNA) relationship among them was verified by dual-luciferase reporter assay. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and colony formation assays, transwell assays, and flow cytometry were used to examine cell proliferation, migration and invasion, and apoptosis, respectively. Levels of proliferation and invasion-related markers were determined by western blot. Xenograft assay was performed to assess tumor growth. Circ_RNF10 level was significantly reduced in BC tissues and cells. Elevation of circ_RNF10 blocked BC cell proliferation, migration and invasion while promoted the apoptosis in vitro, companied with decreased PCNA and Twist1 and increased E-cadherin. Furthermore, upregulating circ_RNF10 delayed tumor growth of BC cells in nude mice. Mechanistically, circ_RNF10 acted as a ceRNA for miR-942-5p, and miR-942-5p could target GOLIM4. In addition, miR-942-5p overexpression reversed the influence of circ_RNF10 overexpression on BC progression. Furthermore, GOLIM4 silencing attenuated the inhibitory effect of miR-942-5p knockdown on BC progression. We found that circ_RNF10 suppressed BC malignant behavior by targeting miR-942-5p/GOLIM4 axis.
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Affiliation(s)
- Binghua Kan
- Surgical Oncology, Hanzhong Central Hospital, Hanzhong, China
| | - Guiru Yan
- Surgical Oncology, Hanzhong Central Hospital, Hanzhong, China
| | - Yuan Shao
- Surgical Oncology, Hanzhong Central Hospital, Hanzhong, China
| | - Ziliang Zhang
- Surgical Oncology, Hanzhong Central Hospital, Hanzhong, China
| | - Hui Xue
- Oncology Department, Hanzhong Central Hospital, Hanzhong, China
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Li Z, Xie Y, Xiao B, Guo J. The tumor suppressor function of hsa_circ_0006282 in gastric cancer through PTEN/AKT pathway. Int J Clin Oncol 2022; 27:1562-1569. [PMID: 35794253 DOI: 10.1007/s10147-022-02210-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 06/20/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer. METHODS The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis. RESULTS Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p. CONCLUSION By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer.
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Affiliation(s)
- Zhe Li
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China
| | - Yi Xie
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China
| | - Bingxiu Xiao
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China
| | - Junming Guo
- Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China.
- Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China.
- Institute of Digestive Diseases of Ningbo University, Ningbo, 315020, China.
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Factors influencing degradation kinetics of mRNAs and half-lives of microRNAs, circRNAs, lncRNAs in blood in vitro using quantitative PCR. Sci Rep 2022; 12:7259. [PMID: 35508612 PMCID: PMC9068688 DOI: 10.1038/s41598-022-11339-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 04/21/2022] [Indexed: 12/18/2022] Open
Abstract
RNAs are rapidly degraded in samples and during collection, processing and testing. In this study, we used the same method to explore the half-lives of different RNAs and the influencing factors, and compared the degradation kinetics and characteristics of different RNAs in whole blood and experimental samples. Fresh anticoagulant blood samples were incubated at room temperature for different durations, RNAs were extracted, and genes, including internal references, were amplified by real-time quantitative PCR. A linear half-life model was established according to cycle threshold (Ct) values. The effects of experimental operations on RNA degradation before and after RNA extraction were explored. Quantitative analysis of mRNA degradation in samples and during experimental processes were explored using an orthogonal experimental design. The storage duration of blood samples at room temperature had the greatest influence on RNA degradation. The half-lives of messenger RNAs (mRNAs) was 16.4 h. The half-lives of circular RNAs (circRNAs), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were 24.56 ± 5.2 h, 17.46 ± 3.0 h and 16.42 ± 4.2 h, respectively. RNA degradation occurred mainly in blood samples. The half-life of mRNAs was the shortest among the four kinds of RNAs. Quantitative experiments related to mRNAs should be completed within 2 h. The half-lives of circRNAs and lncRNAs were longer than those of the former two.
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Sharma AR, Banerjee S, Bhattacharya M, Saha A, Lee SS, Chakraborty C. Recent progress of circular RNAs in different types of human cancer: Technological landscape, clinical opportunities and challenges (Review). Int J Oncol 2022; 60:56. [PMID: 35362541 DOI: 10.3892/ijo.2022.5346] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 03/10/2022] [Indexed: 11/11/2022] Open
Abstract
Circular RNAs (circRNAs) are a novel class of endogenous non‑coding RNAs that have been recently regarded as functionally active. CircRNAs are remarkably stable and known to possess several biological functions such as microRNA sponging, regulating transcription and splicing and occasionally acting as polypeptide‑producing templates. CircRNAs show tissue‑specific expression and have been reported to be associated with the progression of several types of malignancies. Given the recent progress in genome sequencing and bioinformatics techniques, a rapid increment in the biological role of circRNAs has been observed. Concurrently, the patent search from different patent databases shows that the patent number of circRNA is increasing very quickly. These phenomena reveal a rapid development of the technological landscape. In the present review, the recent progress on circRNAs in various kinds of cancer has been investigated and their function as biomarkers or therapeutic targets and their technological landscape have been appreciated. A new insight into circRNAs structure and functional capabilities in cancer has been reviewed. Continually increasing knowledge on their critical role during cancer progression is projecting them as biomarkers or therapeutic targets for various kinds of cancer. Thus, recent updates on the functional role of circRNAs in terms of the technological landscape, clinical opportunities (biomarkers and therapeutic targets), and challenges in cancer have been illustrated.
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Affiliation(s)
- Ashish Ranjan Sharma
- Institute for Skeletal Aging and Orthopedic Surgery, Hallym University‑Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon 24252, Republic of Korea
| | - Shreya Banerjee
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal 700126, India
| | - Manojit Bhattacharya
- Department of Zoology, Fakir Mohan University, Vyasa Vihar, Balasore, Odisha 756020, India
| | - Abinit Saha
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal 700126, India
| | - Sang-Soo Lee
- Institute for Skeletal Aging and Orthopedic Surgery, Hallym University‑Chuncheon Sacred Heart Hospital, Chuncheon, Gangwon 24252, Republic of Korea
| | - Chiranjib Chakraborty
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal 700126, India
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21
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Feng Z, Li L, Tu Y, Shu X, Zhang Y, Zeng Q, Luo L, Wu A, Chen W, Cao Y, Li Z. Identification of Circular RNA-Based Immunomodulatory Networks in Colorectal Cancer. Front Oncol 2022; 11:779706. [PMID: 35155186 PMCID: PMC8833313 DOI: 10.3389/fonc.2021.779706] [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: 09/19/2021] [Accepted: 12/30/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) have been recently proposed as hub molecules in various diseases, especially in tumours. We found that circRNAs derived from ribonuclease P RNA component H1 (RPPH1) were highly expressed in colorectal cancer (CRC) samples from Gene Expression Omnibus (GEO) datasets. OBJECTIVE We sought to identify new circRNAs derived from RPPH1 and investigate their regulation of the competing endogenous RNA (ceRNA) and RNA binding protein (RBP) networks of CRC immune infiltration. METHODS The circRNA expression profiles miRNA and mRNA data were extracted from the GEO and The Cancer Genome Atlas (TCGA) datasets, respectively. The differentially expressed (DE) RNAs were identified using R software and online server tools, and the circRNA-miRNA-mRNA and circRNA-protein networks were constructed using Cytoscape. The relationship between targeted genes and immune infiltration was identified using the GEPIA2 and TIMER2 online server tools. RESULTS A ceRNA network, including eight circRNAs, five miRNAs, and six mRNAs, was revealed. Moreover, a circRNA-protein network, including eight circRNAs and 49 proteins, was established. The targeted genes, ENOX1, NCAM1, SAMD4A, and ZC3H10, are closely related to CRC tumour-infiltrating macrophages. CONCLUSIONS We analysed the characteristics of circRNA from RPPH1 as competing for endogenous RNA binding miRNA or protein in CRC macrophage infiltration. The results point towards the development of a new diagnostic and therapeutic paradigm for CRC.
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Affiliation(s)
- Zongfeng Feng
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Leyan Li
- Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China.,Queen Mary School, Medical Department of Nanchang University, Nanchang, China
| | - Yi Tu
- Department of Pathology, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xufeng Shu
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yang Zhang
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Qingwen Zeng
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Lianghua Luo
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ahao Wu
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China
| | - Wenzheng Chen
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yi Cao
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhengrong Li
- Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China.,Laboratory of Digestive Surgery, Nanchang University, Nanchang, China.,Medical Innovation Center, the First Affiliated Hospital of Nanchang University, Nanchang, China
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22
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Hu Y, Bian X, Wu C, Wang Y, Wu Y, Gu X, Zhuo S, Sun S. Genome-wide analysis of circular RNAs and validation of hsa_circ_0086354 as a promising biomarker for early diagnosis of cerebral palsy. BMC Med Genomics 2022; 15:13. [PMID: 35062922 PMCID: PMC8783515 DOI: 10.1186/s12920-022-01163-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 01/12/2022] [Indexed: 11/17/2022] Open
Abstract
Background Cerebral palsy (CP) is a spectrum of non-progressive motor disorders caused by brain injury during fetal or postnatal periods. Current diagnosis of CP mainly relies on neuroimaging and motor assessment. Here, we aimed to explore novel biomarkers for early diagnosis of CP. Methods Blood plasma from five children with CP and their healthy twin brothers/sisters was analyzed by gene microarray to screen out differentially expressed RNAs. Selected differentially expressed circular RNAs (circRNAs) were further validated using quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to assess the specificity and sensitivity of hsa_circ_0086354 in discriminating children with CP and healthy controls. Results 43 up-regulated circRNAs and 2 down-regulated circRNAs were obtained by difference analysis (fold change > 2, p < 0.05), among which five circRNAs related to neuron differentiation and neurogenesis were chosen for further validation. Additional 30 pairs of children with CP and healthy controls were recruited and five selected circRNAs were further detected, showing that hsa_circ_0086354 was significantly down-regulated in CP plasma compared with control, which was highly in accord with microarray analysis. ROC curve analysis showed that the area under curve (AUC) to discriminate children with CP and healthy controls using hsa_circ_0086354 was 0.967, the sensitivity was 0.833 and the specificity was 0.966. Moreover, hsa_circ_0086354 was predicted as a competitive endogenous RNA for miR-181a, and hsa_circ_0086354 expression was negatively correlated to miR-181a expression in children with CP. Conclusion Hsa_circ_0086354 was significantly down-regulated in blood plasma of children with CP, which may be a novel competent biomarker for early diagnosis of CP. Supplementary Information The online version contains supplementary material available at 10.1186/s12920-022-01163-6.
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Yuan S, Zheng P, Sun X, Zeng J, Cao W, Gao W, Wang Y, Wang L. Hsa_Circ_0001860 Promotes Smad7 to Enhance MPA Resistance in Endometrial Cancer via miR-520h. Front Cell Dev Biol 2021; 9:738189. [PMID: 34912799 PMCID: PMC8666979 DOI: 10.3389/fcell.2021.738189] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 10/26/2021] [Indexed: 12/30/2022] Open
Abstract
Background: Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed progestin for the treatment of endometrial cancer (EC). Despite initial benefits, many patients ultimately develop progesterone resistance. Circular RNA (circRNA) is a kind of noncoding RNA, contributing greatly to the development of human tumor. However, the role of circular RNA in MPA resistance is unknown. Methods: We explored the expression profile of circRNAs in Ishikawa cells treated with (ISK/MPA) or without MPA (ISK) by RNA sequencing, and identified a key circRNA, hsa_circ_0001860. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify its expression in MPA-resistant cell lines and tissues. CCK8, Transwell, and flow cytometry were used to evaluate the functional roles of hsa_circ_0001860 in MPA resistance. The interaction between hsa_circ_0001860 and miR-520 h was confirmed by bioinformatics analysis, luciferase reporter assay, and RNA pull-down assay. Results: The expression of hsa_circ_0001860 was significantly downregulated in MPA-resistant cell lines and tissues, and negatively correlated with lymph node metastasis and histological grade of EC. Functional analysis showed that hsa_circ_0001860 knockdown by short hairpin RNA (shRNA) promoted the proliferation, inhibited the apoptosis of Ishikawa cells, and promoted the migration and invasion of Ishikawa cells treated with MPA. Mechanistically, hsa_circ_0001860 promoted Smad7 expression by sponging miR-520 h. Conclusion: Hsa_circ_0001860 plays an important role in the development of MPA resistance in EC through miR-520h/Smad7 axis, and it could be targeted to reverse the MPA resistance in endometrial cancer.
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Affiliation(s)
- Shuang Yuan
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Panchan Zheng
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiao Sun
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Municipal Key Clinical Specialty, Shanghai, China.,Shanghai Key Laboratory of Embryo Original Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Judan Zeng
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wenjiao Cao
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wuyuan Gao
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yudong Wang
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Municipal Key Clinical Specialty, Shanghai, China.,Shanghai Key Laboratory of Embryo Original Disease, Shanghai Jiao Tong University, Shanghai, China
| | - Lihua Wang
- Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Rajgopal S, Fredrick SJ, Parvathi VD. CircRNAs: Insights into Gastric Cancer. Gastrointest Tumors 2021; 8:159-168. [PMID: 34722469 DOI: 10.1159/000517303] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 05/19/2021] [Indexed: 01/22/2023] Open
Abstract
Background Gastric cancer (GC) is recorded as the fifth most common cancer globally. The classic resemblance of early symptoms of chronic gastritis including nausea, dysphagia, and dyspepsia with GC is the current challenge limiting the early diagnosis of GC. The current diagnostic procedures of GC are limited due to their invasive nature. This directs the research question toward alternative approaches, specifically at the molecular level. Recent advances in molecular regulation of cancer suggest the prominence of circular RNAs (circRNAs) in the multistep process of tumourigenesis. Summary CircRNAs are a class of non-coding RNAs, abundant in eukaryotes, with key roles in regulating genes and miRNAs as well as the alteration of processes involved in pathological conditions. Research studies have demonstrated the participation of circRNAs in the initiation and progression of tumours. This review provides a comprehensive insight into the potential of circRNAs as disease biomarkers for the early detection and treatment of GC. Key Messages This study is an amalgamation of the implications and future prospects of circRNAs for the detection and potential treatment of GC.
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Affiliation(s)
- Sanjana Rajgopal
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
| | - Sherine Joanna Fredrick
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
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Zhang Y, Wang Y, Su X, Wang P, Lin W. The Value of Circulating Circular RNA in Cancer Diagnosis, Monitoring, Prognosis, and Guiding Treatment. Front Oncol 2021; 11:736546. [PMID: 34722285 PMCID: PMC8551378 DOI: 10.3389/fonc.2021.736546] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 09/23/2021] [Indexed: 12/31/2022] Open
Abstract
Liquid biopsy includes non-invasive analysis of circulating tumor-derived substances. It is a novel, innovative cancer screening tool that overcomes the limitations of current invasive tissue examinations in precision oncology. Circular RNA (circRNA) is a recent, novel, and attractive liquid biomarker showing stability, abundance, and high specificity in various diseases, especially in human cancers. This review focused on the emerging potential of human circRNA in body fluids as the liquid biopsy biomarkers for cancers and the methods used to detect the circRNA expression and summarized the construction of circRNA biomarkers in body fluids for treating human cancers and their limitations before they become part of routine clinical medicine. Furthermore, the future opportunities and challenges of translating circRNAs in liquid biopsy into clinical practices were explored.
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Affiliation(s)
- Yunjing Zhang
- Department of Nephrology, The Fourth Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua, China
| | - Ying Wang
- Department of Nephrology, The Fourth Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua, China
| | - Xinwan Su
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ping Wang
- Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weiqiang Lin
- Department of Nephrology, The Fourth Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Jinhua, China
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Han J, Yang Z, Zhao S, Zheng L, Tian Y, Lv Y. Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression. Eur J Clin Invest 2021; 51:e13592. [PMID: 34032284 DOI: 10.1111/eci.13592] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Increasing evidence has shown that circular RNAs (circRNAs) serve as vital regulators in tumour progression. In this study, we focused on the functions of circ_0027599 in gastric cancer (GC) progression. METHODS The levels of circ_0027599, runt-related transcription factor 1 (RUNX1) mRNA and microRNA-21-5p (miR-21-5p) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The protein levels of RUNX1, E-Cadherin, vimentin and N-Cadherin were measured by Western blot assay. Cell viability, colony formation, metastasis and cell cycle process were evaluated by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay and flow cytometry analysis, respectively. The interaction between circ_0027599 and miR-21-5p and the interaction between miR-21-5p and RUNX1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circ_0027599 in tumour growth in vivo was investigated by murine xenograft model assay. RESULTS Circ_0027599 and RUNX1 were downregulated in GC tissues and cells. Circ_0027599 level was associated with the overall survival of GC patients. Circ_0027599 or RUNX1 overexpression inhibited GC cell viability, colony formation, migration, invasion and cell cycle process in vitro. For mechanism analysis, circ_0027599 positively regulated RUNX1 expression via functioning as the sponge for miR-21-5p. RUNX1 inhibition reversed circ_0027599 overexpression mediated malignant behaviours of GC cells. Moreover, circ_0027599 overexpression repressed tumour growth in vivo. CONCLUSION Circ_0027599 overexpression repressed GC progression via modulation of miR-21-5p/RUNX1 axis, which might illumine a novel therapeutic target for GC.
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Affiliation(s)
- Jinzhu Han
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zixin Yang
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shan Zhao
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Likang Zheng
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yanhua Tian
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yingqian Lv
- The Second Department of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
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27
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Liu W, Hu W, Hou K, Zhu S. Circular RNA Paired-Related Homeobox 1 Promotes Gastric Carcinoma Cell Progression via Regulating MicroRNA-665/YWHAZ Axis. Dig Dis Sci 2021; 66:3842-3853. [PMID: 33201331 DOI: 10.1007/s10620-020-06705-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gastric carcinoma (GC) is a ubiquitous malignant tumor worldwide. Circular RNA paired-related homeobox 1 (circ-PRRX1), one kind of non-coding RNAs, has been reported to act as a promoter in tumor growth. This study aims to explore the effects of circ-PRRX1 on proliferation, apoptosis, and metastasis in GC and the underlying regulatory mechanisms. METHODS The expression of circ-PRRX1, miR-665, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze YWHAZ protein expression. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-Htetrazolium bromide (MTT), flow cytometry, and transwell assay were carried out to assess the viability, apoptosis, migration, and invasion in GC cells. The interaction between miR-665 and circ-PRRX1 or YWHAZ was predicted by StarBase v2.0 and identified by dual-luciferase reporter system. Xenograft mouse model was employed to determine the effects of circ-PRRX1 knockdown on GC growth in vivo. RESULTS Compared with normal tissues and cells, circ-PRRX1 and YWHAZ levels were upregulated, and miR-665 was downregulated in GC tissues and cells. Functionally, circ-PRRX1 knockdown inhibited the viability, migration, and invasion and promoted apoptosis in GC cells, whereas anti-miR-665 abolished these effects. Mechanistically, circ-PRRX1 was confirmed as a sponge of miR-665 to regulate YWHAZ expression. Xenograft mouse model suggested that circ-PRRX1 knockdown reduced GC cells growth in vivo. CONCLUSION Circ-PRRX1 knockdown suppressed GC development by targeting miR-665 to inhibit YWHAZ expression, and the potential molecular mechanism may provide a theoretical basis for GC therapy.
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Affiliation(s)
- Wei Liu
- Department of General Surgery, Shidong Hospital, No. 999, Shiguang Road, Shanghai, 200438, China
| | - Weigao Hu
- Department of General Surgery, Shidong Hospital, No. 999, Shiguang Road, Shanghai, 200438, China
| | - Kezhu Hou
- Department of General Surgery, Shidong Hospital, No. 999, Shiguang Road, Shanghai, 200438, China
| | - Song Zhu
- Department of General Surgery, Shidong Hospital, No. 999, Shiguang Road, Shanghai, 200438, China.
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Lu Y, Li K, Gao Y, Liang W, Wang X, Chen L. CircRNAs in gastric cancer: current research and potential clinical implications. FEBS Lett 2021; 595:2644-2654. [PMID: 34561854 DOI: 10.1002/1873-3468.14196] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 09/04/2021] [Accepted: 09/14/2021] [Indexed: 12/11/2022]
Abstract
Gastric cancer (GC) has a dismal prognosis and is also one of the most commonly diagnosed malignancies worldwide. circRNAs are covalently closed circular RNA molecules without 5'-cap and a 3'-tail, currently listed among the broad noncoding RNA family. circRNAs participate in a variety of pathophysiological processes relevant to human diseases, especially malignancies, including GC. Compelling evidence has shown that circRNAs can function by sponging miRNAs, interacting with RNA binding proteins, and encoding proteins or peptides. Yet, our current understanding of these RNA circles remains very limited. Here, we overview the biogenesis, characteristics, functions, and degradation of circRNAs. Moreover, we give an account of the circRNAs that have been linked with GC, describing their functions and mechanisms of action in the context of GC. Next, we discuss the potential value of circRNAs as diagnostic or prognostic GC biomarkers and summarize future prospects, important questions, and challenges of circRNA-based therapeutics.
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Affiliation(s)
- Yixun Lu
- Medical School of Chinese PLA, Beijing, China
- Department & Institute of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Kai Li
- Medical School of Chinese PLA, Beijing, China
- Department & Institute of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yunhe Gao
- Department & Institute of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wenquan Liang
- Department & Institute of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xinxin Wang
- Department & Institute of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Lin Chen
- Department & Institute of General Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing, China
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Mafi A, Yadegar N, Salami M, Salami R, Vakili O, Aghadavod E. Circular RNAs; powerful microRNA sponges to overcome diabetic nephropathy. Pathol Res Pract 2021; 227:153618. [PMID: 34649056 DOI: 10.1016/j.prp.2021.153618] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 09/09/2021] [Accepted: 09/11/2021] [Indexed: 12/13/2022]
Abstract
Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a drastic renal complication of type 1 and type 2 diabetes mellitus (DM). Poorly controlled DM over the years, may disrupt kidneys' blood vessels, leading to the hypertension (HTN) and DN onset. During DN, kidneys' waste filtering ability becomes disturbed. Being on a healthy lifestyle and controlling both DM and HTN are now the best proceedings to prevent or at least delay DN occurrence. Unfortunately, about one-fourth of diabetic individuals eventually experience the corresponding renal failure, and thus it is critical to discover effective diagnostic biomarkers and therapeutic strategies to combat DN. In the past few years, circular RNAs (circRNAs), as covalently closed endogenous non-coding RNAs (ncRNAs), are believed to affect DN pathogenesis in a positive manner. CircRNAs are able to impact different cellular processes and signaling pathways by targeting biological molecules or various molecular mechanisms. Still, as a key regulatory axis, circRNAs can select miRNAs as their molecular targets, in which they are considered as miRNA sponges. In this way, circRNA-induced suppression of particular miRNAs may prevent from DN progression or promotes the DN elimination. Since the expression of circRNAs has also been reported to be increased in DN-associated cells and tissues, they can be employed as either diagnostic biomarkers or therapeutic targets.
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Affiliation(s)
- Alireza Mafi
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Negar Yadegar
- Department of Medical Laboratory Sciences, School of Paramedical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Marziyeh Salami
- Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
| | - Raziyeh Salami
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
| | - Omid Vakili
- Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Esmat Aghadavod
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran; Department of Clinical Biochemistry, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
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Yang F, Ma C, Qiu J, Feng X, Yang K. Identification of circRNA_001846 as putative non-small cell lung cancer biomarker. Bioengineered 2021; 12:8690-8697. [PMID: 34635012 PMCID: PMC8806949 DOI: 10.1080/21655979.2021.1991161] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
CircRNAs play diverse roles in the regulation of oncogenic processes, yet the roles of these circRNAs in non-small cell lung cancer (NSCLC) remain to be fully clarified. Herein, patterns of circRNA expression in NSCLC tissues and paracancerous tissues were assessed, and the relationships between these circRNAs and NSCLC patient clinical findings were assessed. NSCLC tissues were evaluated using a circRNA microarray approach, with Quantitative real‑time polymerase chain reaction (qPCR) qPCR being used to validate candidate circRNA expression levels in NSCLC patients peripheral blood samples. GEO2R was used to analyze the array data. SPSS23.0, GraphPad Prism, and Sigmaplot were utilized for statistical analyses. Overall, 114 circRNAs that were differentially expressed in NSCLC tissue relative to paracancerous tissue levels were identified, of which 77 and 37 were downregulated and upregulated, respectively. CircRNA_001846 were then chosen based on its differential expression score. Consistent with array findings, serum samples from NSCLC patients exhibited circRNA_001846 upregulation relative to those from healthy individuals. The circRNA_001846 was associated with tumor differentiation, lymph node metastasis, and node metastasis stage. Receiver operating characteristic (ROC) curves analyses revealed that levels of circRNA_001846 in the serum were capable of differentiating between individuals diagnosed with NSCLC and controls at a cut off of 3.9496, yielding respective sensitivity and specificity values of 78.2% and 81.1%, with an area under the curve (AUC) value of 0.872. When combined with carcinoembryonic antigen (CEA), this circRNA achieved an improved AUC value of 0.925. CircRNA_001846 may represent a promising diagnostic biomarker for NSCLC.
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Affiliation(s)
- Fan Yang
- Chengdu Medical College, No. 783, Xindu Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Key Laboratory of Geriatic Respiratory Diseases of Sichuan Higher Education Institutes, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China
| | - Chunlan Ma
- Chengdu Medical College, No. 783, Xindu Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Key Laboratory of Geriatic Respiratory Diseases of Sichuan Higher Education Institutes, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China
| | - Jing Qiu
- Chengdu Medical College, No. 783, Xindu Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Key Laboratory of Geriatic Respiratory Diseases of Sichuan Higher Education Institutes, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China
| | - Xiaoli Feng
- Chengdu Medical College, No. 783, Xindu Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Key Laboratory of Geriatic Respiratory Diseases of Sichuan Higher Education Institutes, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China
| | - Kai Yang
- Chengdu Medical College, No. 783, Xindu Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China.,Key Laboratory of Geriatic Respiratory Diseases of Sichuan Higher Education Institutes, No. 278, Baoguang Avenue, Xindu District, Chengdu (610500), Sichuan. China
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31
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Herrera-Pariente C, Montori S, Llach J, Bofill A, Albeniz E, Moreira L. Biomarkers for Gastric Cancer Screening and Early Diagnosis. Biomedicines 2021; 9:biomedicines9101448. [PMID: 34680565 PMCID: PMC8533304 DOI: 10.3390/biomedicines9101448] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/06/2021] [Accepted: 10/08/2021] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer is one of the most common cancers worldwide, with a bad prognosis associated with late-stage diagnosis, significantly decreasing the overall survival. This highlights the importance of early detection to improve the clinical course of these patients. Although screening programs, based on endoscopic or radiologic approaches, have been useful in countries with high incidence, they are not cost-effective in low-incidence populations as a massive screening strategy. Additionally, current biomarkers used in daily routine are not specific and sensitive enough, and most of them are obtained invasively. Thus, it is imperative to discover new noninvasive biomarkers able to diagnose early-stage gastric cancer. In this context, liquid biopsy is a promising strategy. In this review, we briefly discuss some of the potential biomarkers for gastric cancer screening and diagnosis identified in blood, saliva, urine, stool, and gastric juice.
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Affiliation(s)
- Cristina Herrera-Pariente
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain; (C.H.-P.); (J.L.); (A.B.)
| | - Sheyla Montori
- UPNA, IdiSNA, Navarrabiomed Biomedical Research Center, Gastrointestinal Endoscopy Research Unit, 31008 Pamplona, Spain; (S.M.); (E.A.)
| | - Joan Llach
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain; (C.H.-P.); (J.L.); (A.B.)
| | - Alex Bofill
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain; (C.H.-P.); (J.L.); (A.B.)
| | - Eduardo Albeniz
- UPNA, IdiSNA, Navarrabiomed Biomedical Research Center, Gastrointestinal Endoscopy Research Unit, 31008 Pamplona, Spain; (S.M.); (E.A.)
- Endoscopy Unit, Gastroenterology Department, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain
| | - Leticia Moreira
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain; (C.H.-P.); (J.L.); (A.B.)
- Correspondence:
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Ghafouri-Fard S, Honarmand Tamizkar K, Jamali E, Taheri M, Ayatollahi SA. Contribution of circRNAs in gastric cancer. Pathol Res Pract 2021; 227:153640. [PMID: 34624593 DOI: 10.1016/j.prp.2021.153640] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 09/22/2021] [Accepted: 09/27/2021] [Indexed: 12/13/2022]
Abstract
Gastric cancer (GC) is one of the most commonly diagnosed neoplasms in the world. A number of environmental and lifestyle factors, particularly chronic infection with Helicobacter pylori, have been found to partake in the pathogenesis of GC. The advent of high-throughput genome and transcriptome analysis has enhanced the knowledge about molecular mechanisms of the pathogenesis of GC. However, data regarding the expression of several circRNAs, such as circLMTK2, are not consistent. We explain the role of circRNAs in the development of GC. We searched databases for the newest publications using the terms gastric cancer and circRNA. Each circRNA alteration, downstream targets, its impacts on cancer cells, and the prognostic and diagnostic roles of these circRNAs have been discussed. Taken together, circRNAs can be putative biomarkers in GC and potential targets for the treatment of this cancer. Yet, this field is still in its infancy and needs further experiments for reaching the clinical application. As these transcripts are stable in circulation, they can be used in non-invasive methods of cancer detection and patients' follow-up.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kasra Honarmand Tamizkar
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elena Jamali
- Department of Pathology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Li D, Li L, Chen X, Yang W, Cao Y. Circular RNA SERPINE2 promotes development of glioblastoma by regulating the miR-361-3p/miR-324-5p/ BCL2 signaling pathway. MOLECULAR THERAPY-ONCOLYTICS 2021; 22:483-494. [PMID: 34553034 PMCID: PMC8433060 DOI: 10.1016/j.omto.2021.07.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 07/25/2021] [Indexed: 01/26/2023]
Abstract
Circular RNA (circRNA) is a new type of long-sequence RNA formed by a noncanonical form of alternative splicing called back-splicing. Emerging evidence has revealed that circRNAs are involved in cancer progression, regulating cancer-related genes through sponging microRNAs (miRNAs). In our study, we identified a novel upregulated circRNA, circSERPINE2, through analyzing circRNAs microarray data of glioblastoma from GEO datasets (GSE146463). Quantitative real-time PCR was used to further confirm the upregulation of circSERPINE2 in glioblastoma cell lines and tissues. Silencing circSERPINE2 inhibits glioblastoma proliferation in vivo and in vitro through cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, and western blot analysis and xenograft tumor model. Mechanistically, circSERPINE2 could directly sponge miR-324-5p and miR-361-3p. BCL2, known as a novel anti-apoptosis gene, is a target gene both of miR-324-5p and miR-361-3p. Thus, circSERPINE2 promotes BCL2 expression through sponging miR-324-5p and miR-361-3p. In conclusion, our study revealed the biological function and mechanism of circSERPINE2 in glioblastoma progression and that circSERPINE2 could be a potential therapeutic target for glioblastoma.
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Affiliation(s)
- Deheng Li
- Department of Neurosurgery, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, Shanghai 200032, P.R. China
| | - Liangdong Li
- Department of Neurosurgery, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, Shanghai 200032, P.R. China
| | - Xin Chen
- Department of Neurosurgery, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, Shanghai 200032, P.R. China
| | - Wentao Yang
- Department of Pathology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, Shanghai 200032, P.R. China
| | - Yiqun Cao
- Department of Neurosurgery, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, Shanghai 200032, P.R. China
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Sharma AR, Bhattacharya M, Bhakta S, Saha A, Lee SS, Chakraborty C. Recent research progress on circular RNAs: Biogenesis, properties, functions, and therapeutic potential. MOLECULAR THERAPY. NUCLEIC ACIDS 2021; 25:355-371. [PMID: 34484862 PMCID: PMC8399087 DOI: 10.1016/j.omtn.2021.05.022] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Circular RNAs (circRNAs), an emerging family member of RNAs, have gained importance in research due to their new functional roles in cellular physiology and disease progression. circRNAs are usually available in a wide range of cells and have shown tissue-specific expression as well as developmental specific expression. circRNAs are characterized by structural stability, conservation, and high abundance in the cell. In this review, we discuss the different models of biogenesis. The properties of circRNAs such as localization, structure and conserved pattern, stability, and expression specificity are also been illustrated. Furthermore, we discuss the biological functions of circRNAs such as microRNA (miRNA) sponging, cell cycle regulation, cell-to-cell communication, transcription regulation, translational regulation, disease diagnosis, and therapeutic potential. Finally, we discuss the recent research progress and future perspective of circRNAs. This review provides an understanding of potential diagnostic markers and the therapeutic potential of circRNAs, which are emerging daily.
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Affiliation(s)
- Ashish Ranjan Sharma
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Republic of Korea
| | - Manojit Bhattacharya
- Department of Zoology, Fakir Mohan University, Vyasa Vihar, Balasore 756020, Odisha, India
| | - Swarnav Bhakta
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Road, Jagannathpur, Kolkata, West Bengal 700126, India
| | - Abinit Saha
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Road, Jagannathpur, Kolkata, West Bengal 700126, India
| | - Sang-Soo Lee
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Republic of Korea
| | - Chiranjib Chakraborty
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Barasat-Barrackpore Road, Jagannathpur, Kolkata, West Bengal 700126, India
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Tao M, Zheng M, Xu Y, Ma S, Zhang W, Ju S. CircRNAs and their regulatory roles in cancers. Mol Med 2021; 27:94. [PMID: 34445958 PMCID: PMC8393742 DOI: 10.1186/s10020-021-00359-3] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 08/18/2021] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It’s particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned.
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Affiliation(s)
- Mei Tao
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No.20, Nantong, 226001, Jiangsu, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.,Medical School of Nantong University, Nantong University, Nantong, 226001, Jiangsu, China
| | - Ming Zheng
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No.20, Nantong, 226001, Jiangsu, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.,Medical School of Nantong University, Nantong University, Nantong, 226001, Jiangsu, China
| | - Yanhua Xu
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No.20, Nantong, 226001, Jiangsu, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.,Medical School of Nantong University, Nantong University, Nantong, 226001, Jiangsu, China
| | - Shuo Ma
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No.20, Nantong, 226001, Jiangsu, China.,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.,Medical School of Nantong University, Nantong University, Nantong, 226001, Jiangsu, China
| | - Weiwei Zhang
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No.20, Nantong, 226001, Jiangsu, China. .,Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
| | - Shaoqing Ju
- Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No.20, Nantong, 226001, Jiangsu, China.
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Zhou Y, Ma G, Peng S, Tuo M, Li Y, Qin X, Yu Q, Kuang S, Cheng H, Li J. Circ_0000520 contributes to triple-negative breast cancer progression through mediating the miR-1296/ZFX axis. Thorac Cancer 2021; 12:2427-2438. [PMID: 34324278 PMCID: PMC8447912 DOI: 10.1111/1759-7714.14085] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/02/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
Background Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high incidence of local recurrence and metastasis. Circular RNAs (circRNAs) are implicated in the pathomechanism of TNBC. Here, we investigated the function of circ_0000520 in TNBC and its associated mechanism. Methods Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) and Western blot assay were used to measure RNA and protein expression. Cell proliferation was analyzed by cell counting kit‐8 (CCK8) assay, flow cytometry and colony formation assay. Cell apoptosis was assessed by flow cytometry. Cell migration ability was analyzed by transwell migration and wound healing assays. Transwell invasion assay was conducted to analyze the invasion ability. Dual‐luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA‐pulldown assay were performed to verify the interaction between microRNA‐1296 (miR‐1296) and circ_0000520 or zinc finger protein X‐linked (ZFX). Xenograft mice model was established to analyze the role of circ_0000520 in xenograft tumor growth in vivo. Results Circ_0000520 expression was upregulated in TNBC tissues and cell lines. Circ_0000520 knockdown suppressed the proliferation, migration, and invasion whereas induced the apoptosis of TNBC cells. miR‐1296 was verified as a target of circ_0000520, and circ_0000520 silencing‐mediated suppressive effects on the malignant potential of TNBC cells were partly overturned by miR‐1296 knockdown. miR‐1296 interacted with the 3′ untranslated region (3′UTR) of ZFX, and ZFX overexpression partly reversed miR‐1296 overexpression‐mediated effects in TNBC cells. Circ_0000520 absence reduced ZFX expression by upregulating miR‐1296 in TNBC cells. Circ_0000520 silencing suppressed xenograft tumor growth in vivo. Conclusions Circ_0000520 contributed to TNBC development by binding to miR‐1296 to induce ZFX expression.
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Affiliation(s)
- Yong Zhou
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Guoxi Ma
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Shijun Peng
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Min Tuo
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Yinmou Li
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Xianxiong Qin
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Qiang Yu
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Sijie Kuang
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Hong Cheng
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
| | - Jing Li
- Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, China
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Lyu J, Li H, Yin D, Zhao M, Sun Q, Guo M. Analysis of eight bile acids in urine of gastric cancer patients based on covalent organic framework enrichment coupled with liquid chromatography-tandem mass spectrometry. J Chromatogr A 2021; 1653:462422. [PMID: 34348207 DOI: 10.1016/j.chroma.2021.462422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/14/2021] [Accepted: 07/16/2021] [Indexed: 12/12/2022]
Abstract
Gastric carcinoma is one of the most common and deadly forms of cancer. Early detection is critical for successful treatment of gastric cancer, and examination of BAs in urine may provide a critical diagnostic tool for identifying gastric cancer at stages when it can still be cured. Bile acids (BAs) are a crucial toxic factor correlated with the injury of gastric mucosa and as such, quantifying the amount of BA in patient's urine could provide a new means to quickly and non-invasively identify the presence of gastric cancer in the early stages. Here, a covalent organic framework (COF) material synthesized on the basis of 1,3,5-tris(4-nitrophenyl)benzene (TAPB) and pyromellitic dianhydride (PMDA) was used as stationary phase for SPE column that was coupled to LC-MS/MS for quantitative analysis of eight BAs in human urine, including cholic acid (CA), deoxycholic acid (DCA), glycochenodeoxycholic acid (GCDCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), lithocholic acid (LCA), hyodeoxycholic acid (HDCA), and chenodeoxycholic acid (CDCA). The enrichment effect of synthesized COF material was better than commercial SPE and HLB column. The sensitivity can increase 9.37- to 54.30- fold (calculated by the ratio of peak area between before and after enrichment). The probable mechanism is due to the great porosity and the similar polarity with BAs of the COF material. By compared with previous literatures, our method had the minimum limit of detection, which achieved 46.40, 25.75, 47.40, 47.37, 30.42, and 33.92 pg /mL, respectively, for GCA, GCDCA, CA, CDCA, HDCA and DCA after enrichment. These eight BAs also accomplished excellent linearity from 0.34 to 10,000 ng/mL. This material was successfully applied in the measurements of these six BAs in human urine from 76 gastric cancer patients and 32 healthy people. Compared to healthy people, levels of CA, CDCA, DCA, and HDCA were significantly elevated and levels of GCDCA were depressed, respectively, in gastric cancer patients. Our work suggests that these acids may act as potential biomarkers for gastric cancer and our framework provides a method for "non-invasive" diagnosis of gastric cancer.
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Affiliation(s)
- Jinxiu Lyu
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Haijuan Li
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Dengyang Yin
- Jingjiang People's Hospital, Taizhou, Jiangsu, 214500, China
| | - Meng Zhao
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Qiang Sun
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China
| | - Mengzhe Guo
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
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Zheng Q, Zhang J, Zhang T, Liu Y, Du X, Dai X, Gu D. Hsa_circ_0000520 overexpression increases CDK2 expression via miR-1296 to facilitate cervical cancer cell proliferation. J Transl Med 2021; 19:314. [PMID: 34284793 PMCID: PMC8290540 DOI: 10.1186/s12967-021-02953-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 06/19/2021] [Indexed: 01/04/2023] Open
Abstract
Background Circular RNA (circRNA) has been demonstrated to participate in cervical cancer development. In this study, we analyzed the role of hsa_circ_0000520 in cervical cancer. Methods Fifty-two pairs of cervical cancer and adjacent normal tissue samples were collected, and five human cervical cancer cell lines were obtained followed by the detection of hsa_circ_0000520 expression. Nuclear-cytoplasmic isolation and fluorescence in situ hybridization were performed to analyze the subcellular localization of hsa_circ_0000520 while linear RNA was digested by RNase R. Gain- or loss-of function experiments on hsa_circ_0000520 were performed, followed by detection of cell proliferation and cell cycle by EdU, Cell Counting Kit-8, colony formation assay, and flow cytometry respectively. Results Hsa_circ_0000520 and cyclin-dependent kinase 2 (CDK2) were highly expressed in cervical cancer tissues. Binding sites between microRNA-1296 (miR-1296) and hsa_circ_0000520 or CDK2 were verified. Antibody to Argonaute 2 (Ago2) could precipitate hsa_circ_0000520, indicating that hsa_circ_0000520 could competitively bind to miR-1296 via Ago2. Silencing hsa_circ_0000520 inhibited cervical cancer cell proliferation and promoted the inhibitory effects of miR-1296 on CDK2, thereby blocking cell cycle progression and promoting apoptosis. Conclusion These results support the premise that targeting hsa_circ_0000520 can be a potential approach to combat cervical cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-02953-9.
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Affiliation(s)
- Qingling Zheng
- Department of Obstetrics and Gynecology, School of Medicine, Huzhou University, Huzhou, 313000, People's Republic of China
| | - Jin Zhang
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Ting Zhang
- Department of Pathology, School of Medicine, Huzhou University, Huzhou, 313000, People's Republic of China
| | - Yanxiang Liu
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Xiuluan Du
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Xin Dai
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China
| | - Donghua Gu
- Department of Pathology, Suzhou Science & Technology Town Hospital, No. 1, Lijiang Road, Huqiu District, Suzhou, 215153, Jiangsu, People's Republic of China.
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Cheng B, Tian J, Chen Y. Identification of RNA binding protein interacting with circular RNA and hub candidate network for hepatocellular carcinoma. Aging (Albany NY) 2021; 13:16124-16143. [PMID: 34133325 PMCID: PMC8266373 DOI: 10.18632/aging.203139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 05/18/2021] [Indexed: 12/12/2022]
Abstract
The interaction between RNA binding protein (RBP) and circular RNA (circRNA) is important for the regulation of tumor progression. This study aimed to identify the RBP-circRNA network in hepatocellular carcinoma (HCC). 22 differentially expressed (DE) circRNAs in HCC were screened out from Gene Expression Omnibus (GEO) database and their binding RBPs were predicted by Circular RNA Interactome. Among them, 17 DERBPs, which were commonly dysregulated in HCC from The Clinical Proteomic Tumor Analysis Consortium (CPTAC), The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects, were utilized to construct the RBP-circRNA network. Through survival analysis, we found TARDBP was the only prognostic RBP for HCC in CPTAC, TCGA and ICGC projects. High expression of TARDBP was correlated with high grade, advanced stage and low macrophage infiltration of HCC. Additionally, gene set enrichment analysis showed that dysregulated TARDBP might be involved in some pathways related to the HCC pathogenesis. Therefore, a hub RBP-circRNA network was generated based on TARDBP. RNA immunoprecipitation and RNA pull-down confirmed that hsa_circ_0004913 binds to TARDBP. These findings indicated certain RBP-circRNA regulatory network potentially involved in the pathogenesis of HCC, which provides novel insights into the mechanism study and biomarker identification for HCC.
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Affiliation(s)
- Binglin Cheng
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province 510515, China
| | - Jingdong Tian
- School of Biomedical Engineering, Xinhua College of Sun Yat-Sen University, Guangzhou, Guangdong Province 510520, China
| | - Yuhan Chen
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China
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Shi H, Huang S, Qin M, Xue X, Guo X, Jiang L, Hong H, Fang J, Gao L. Exosomal circ_0088300 Derived From Cancer-Associated Fibroblasts Acts as a miR-1305 Sponge and Promotes Gastric Carcinoma Cell Tumorigenesis. Front Cell Dev Biol 2021; 9:676319. [PMID: 34124064 PMCID: PMC8188357 DOI: 10.3389/fcell.2021.676319] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 04/26/2021] [Indexed: 01/22/2023] Open
Abstract
Cancer-associated fibroblast (CAF)-derived exosomes play a major role in gastric carcinoma (GC) tumorigenesis. However, the mechanism behind the activity of circular RNAs in CAF-derived exosomes in GC remains unclear. In the present study, we identified differentially expressed circ_0088300 in GC tissues and plasma exosomes. We found that CAFs delivered functional circ_0088300 to GC tumor cells via exosomes and promoted the proliferation, migration and invasion abilities of GC cells. Furthermore, we demonstrated that circ_0088300 packaging into exosomes was driven by KHDRBS3. In addition, we verified that circ_0088300 served as a sponge that directly targeted miR-1305 and promoted GC cell proliferation, migration and invasion. Finally, the JAK/STAT signaling pathway was found to be involved in the circ_0088300/miR-1305 axis, which accelerates GC tumorigenesis. In conclusion, our results indicated a previously unknown regulatory pathway in which exosomal circ_0088300 derived from CAFs acts as a sponge of miR-1305 and promotes GC cell proliferation, migration and invasion; these data identify a potential biomarker and novel therapeutic target for GC in the future.
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Affiliation(s)
- Hao Shi
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shan Huang
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Mingde Qin
- The Stem Cell and Biomedical Material Key Laboratory of Jiangsu Province (The State Key Laboratory Incubation Base), Soochow University, Suzhou, China
| | - Xiaofeng Xue
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xingpo Guo
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Linhua Jiang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Han Hong
- Department of Hepato-Pancreato-Biliary Surgery, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Jian Fang
- Department of General Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, China
| | - Ling Gao
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
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Yu X, Wang M, Zhao H, Cao Z. Targeting a novel hsa_circ_0000520/miR-556-5p/NLRP3 pathway-mediated cell pyroptosis and inflammation attenuates ovalbumin (OVA)-induced allergic rhinitis (AR) in mice models. Inflamm Res 2021; 70:719-729. [PMID: 34028600 DOI: 10.1007/s00011-021-01472-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/09/2021] [Accepted: 05/11/2021] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVES The circRNAs-miRNAs-mRNAs competing endogenous RNA (ceRNA) networks involve in regulating the development of various inflammation-associated diseases, including allergic rhinitis (AR), and the present study aimed to identify novel AR-associated ceRNA networks. METHODS The mRNA and protein levels of the associated genes were, respectively, examined by real-time qPCR and western blot analysis. The targeting sites in miR-556-5p and NLRP3 were validated by performing dual-luciferase reporter gene system assay. ELISA was used to measure inflammatory cytokines secretion, and CCK-8 assay was conducted to determine cell proliferation. RESULTS Here, we first identified a hsa_circ_0000520/miR-556-5p/NLRP3 signaling cascade triggered epithelium pyroptosis and inflammation to regulate the development of AR in cellular and mice models. Specifically, the pyroptosis-associated biomarkers (NLRP3, ASC, IL-1β and IL-18) and pro-inflammatory cytokines (OVA-specific IgE, TNF-α, IL-4 and IL-5) were upregulated in the nasal subjects collected from AR patients and ovalbumin (OVA)-induced AR mice models, compared to their normal counterparts. Next, using the ceRNA networks analysis software, we screened out a hsa_circ_0000520/miR-556-5p axis that potentially regulated NLRP3 in the human nasal epithelial cell line. Mechanistically, miR-556-5p targeted both hsa_circ_0000520 and 3' untranslated region (3'UTR) of NLRP3, and knock-down of hsa_circ_0000520 inactivated NLRP3-mediated epithelium pyroptosis through miR-556-5p in a ceRNA-dependent manner. Furthermore, we proved that both hsa_circ_0000520 ablation and miR-556-5p overexpression suppressed NLRP3-mediated cell pyroptosis to attenuate AR in mice models. CONCLUSIONS Taken together, we evidenced that targeting the hsa_circ_0000520/miR-556-5p/NLRP3 signaling pathway was a novel AQ1strategy to ameliorate AR progression; however, future clinical data are still required to validate our preliminary results.
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Affiliation(s)
- Xiaofeng Yu
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Shenyang, 110004, China
| | - Meng Wang
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Shenyang, 110004, China
| | - He Zhao
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Shenyang, 110004, China
| | - Zhiwei Cao
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Shenyang, 110004, China.
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Cui X, Feng J, Wu J, Zhang X, Ding M. Propofol postpones colorectal cancer development through circ_0026344/miR-645/Akt/mTOR signal pathway. Open Med (Wars) 2021; 16:570-580. [PMID: 33869779 PMCID: PMC8034241 DOI: 10.1515/med-2021-0254] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 02/04/2021] [Accepted: 02/26/2021] [Indexed: 12/26/2022] Open
Abstract
Colorectal cancer (CRC) is responsible for thousands of slow and painful annual deaths. Propofol, an anesthetic, is commonly used in CRC surgery. The role of circularRNA0026344 (circ_0026344) in propofol-treated CRC remains unclear, which was further explored in this study. Real-time polymerase chain reaction (qPCR) was used to detect the expression of circ_0026344 and microRNA645 (miR-645) in CRC cells and normal cells. Western blot was devoted to testing the protein expression of phospho-protein kinase B (p-AKT), AKT, phospho-mammalian target of rapamycin (p-mTOR), and mTOR in CRC cells. Moreover, cell counting kit-8 (CCK8), colony formation, flow cytometry, and transwell assays were employed to assess the proliferation, apoptosis, and metastasis in CRC cells. Circinteractome online tool was applied to predict the combination between circ_0026344 and miR-645, which was further verified by dual-luciferase reporter system. circ_0026344 was lowly expressed and miR-645 was abundantly expressed in CRC cells. The relative protein expression of p-AKT/AKT and p-mTOR/mTOR was strikingly elevated by si-circ#1, which could be reversed by anti-miR-645 in propofol-treated CRC cells. circ_0026344 overexpression inhibited the proliferation and metastasis and promoted apoptosis in CRC cells. Propofol treatment induced the restraint in proliferation and metastasis and stimulation in apoptosis, which were allayed by si-circ#1; meanwhile, this alleviation could further be abolished by anti-miR-645 in CRC cells. Furthermore, circ_0026344 sponged miR-645 to inhibited Akt/mTOR signal pathway in propofol-treated CRC cells. Propofol postponed CRC process by circ_0026344/miR-645/Akt/mTOR axis. This finding might provide a possibility to improve the therapy of CRC with propofol.
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Affiliation(s)
- Xiaomin Cui
- Department of Postanesthesia Care Unit, The Affiliated Hospital of Kangda College of Nanjing Medical University (The First People's Hospital of Lianyungang), Lianyungang, Jiangsu, China
| | - Jiying Feng
- Department of Anesthesiology, The Affiliated Hospital of Kangda College of Nanjing Medical University (The First People's Hospital of Lianyungang), Lianyungang, Jiangsu, China
| | - Jian Wu
- Department of Emergency, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China
| | - Xiaobao Zhang
- Department of Anesthesiology, The Affiliated Hospital of Kangda College of Nanjing Medical University (The First People's Hospital of Lianyungang), Lianyungang, Jiangsu, China
| | - Mengyao Ding
- Department of Anesthesiology, The Affiliated Hospital of Kangda College of Nanjing Medical University (The First People's Hospital of Lianyungang), No. 188 Jianshe East Road, Lianyungang, 222002, Jiangsu, China
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Wang J, Zhang Y, Liu L, Yang T, Song J. Circular RNAs: new biomarkers of chemoresistance in cancer. Cancer Biol Med 2021; 18:j.issn.2095-3941.2020.0312. [PMID: 33738995 PMCID: PMC8185855 DOI: 10.20892/j.issn.2095-3941.2020.0312] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 11/27/2020] [Indexed: 12/17/2022] Open
Abstract
Chemotherapeutics are validated conventional treatments for patients with advanced cancer. However, with continual application of chemotherapeutics, chemoresistance, which is often predictive of poor prognosis, has gradually become a concern in recent years. Circular RNAs (circRNAs), a class of endogenous noncoding RNAs (ncRNAs) with a closed-loop structure, have been reported to be notable targets and markers for the prognosis, diagnosis, and treatment of many diseases, particularly cancer. Although dozens of studies have shown that circRNAs play major roles in drug-resistance activity in tumors, the mechanisms by which circRNAs affect chemoresistance have yet to be explored. In this review, we describe the detailed mechanisms of circRNAs and chemotherapeutics in various cancers and summarize potential therapeutic targets for drug-resistant tumors.
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Affiliation(s)
- Jiaqi Wang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
- Institute of Digestive Diseases of Xuzhou Medical University, Xuzhou 221002, China
| | - Yi Zhang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
| | - Lianyu Liu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
- Institute of Digestive Diseases of Xuzhou Medical University, Xuzhou 221002, China
| | - Ting Yang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
| | - Jun Song
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
- Institute of Digestive Diseases of Xuzhou Medical University, Xuzhou 221002, China
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Nisar S, Bhat AA, Singh M, Karedath T, Rizwan A, Hashem S, Bagga P, Reddy R, Jamal F, Uddin S, Chand G, Bedognetti D, El-Rifai W, Frenneaux MP, Macha MA, Ahmed I, Haris M. Insights Into the Role of CircRNAs: Biogenesis, Characterization, Functional, and Clinical Impact in Human Malignancies. Front Cell Dev Biol 2021; 9:617281. [PMID: 33614648 PMCID: PMC7894079 DOI: 10.3389/fcell.2021.617281] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 01/04/2021] [Indexed: 01/17/2023] Open
Abstract
Circular RNAs (circRNAs) are an evolutionarily conserved novel class of non-coding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome, originally believed to be aberrant RNA splicing by-products with decreased functionality. However, recent advances in high-throughput genomic technology have allowed circRNAs to be characterized in detail and revealed their role in controlling various biological and molecular processes, the most essential being gene regulation. Because of the structural stability, high expression, availability of microRNA (miRNA) binding sites and tissue-specific expression, circRNAs have become hot topic of research in RNA biology. Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3′ poly-(A) tail or 5′ cap, rendering them immune to exonuclease-mediated degradation. Emerging research has identified multifaceted roles of circRNAs as miRNA and RNA binding protein (RBP) sponges and transcription, translation, and splicing event regulators. CircRNAs have been involved in many human illnesses, including cancer and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, due to their aberrant expression in different pathological conditions. The functional versatility exhibited by circRNAs enables them to serve as potential diagnostic or predictive biomarkers for various diseases. This review discusses the properties, characterization, profiling, and the diverse molecular mechanisms of circRNAs and their use as potential therapeutic targets in different human malignancies.
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Affiliation(s)
- Sabah Nisar
- Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Ajaz A Bhat
- Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Mayank Singh
- Dr. B. R. Ambedkar Institute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Arshi Rizwan
- Department of Nephrology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Sheema Hashem
- Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar
| | - Puneet Bagga
- Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Ravinder Reddy
- Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
| | - Farrukh Jamal
- Dr. Rammanohar Lohia Avadh University, Ayodhya, India
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Gyan Chand
- Department of Endocrine Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Davide Bedognetti
- Laboratory of Cancer Immunogenomics, Cancer Research Department, Sidra Medicine, Doha, Qatar.,Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.,College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
| | - Wael El-Rifai
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, United States
| | | | - Muzafar A Macha
- Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology (IUST), Pulwama, India
| | - Ikhlak Ahmed
- Research Branch, Sidra Medicine, Doha, Qatar.,Research Branch, Sidra Medicine, Doha, Qatar
| | - Mohammad Haris
- Functional and Molecular Imaging Laboratory, Cancer Research Department, Sidra Medicine, Doha, Qatar.,Laboratory Animal Research Center, Qatar University, Doha, Qatar
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Tang X, Ren H, Guo M, Qian J, Yang Y, Gu C. Review on circular RNAs and new insights into their roles in cancer. Comput Struct Biotechnol J 2021; 19:910-928. [PMID: 33598105 PMCID: PMC7851342 DOI: 10.1016/j.csbj.2021.01.018] [Citation(s) in RCA: 226] [Impact Index Per Article: 56.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/13/2021] [Accepted: 01/14/2021] [Indexed: 12/13/2022] Open
Abstract
Circular RNAs (circRNAs) are a very interesting class of conserved single-stranded RNA molecules derived from exonic or intronic sequences by precursor mRNA back-splicing. Unlike canonical linear RNAs, circRNAs form covalently closed, continuous stable loops without a 5'end cap and 3'end poly(A) tail, and therefore are resistant to exonuclease digestion. The majority of circRNAs are highly abundant, and conserved across different species with a tissue or developmental-stage-specific expression. circRNAs have been shown to play important roles as microRNA sponges, regulators of gene splicing and transcription, RNA-binding protein sponges and protein/peptide translators. Emerging evidence reveals that circRNAs function in various human diseases, particularly cancers, and may function as better predictive biomarkers and therapeutic targets for cancer treatment. In consideration of their potential clinical relevance, circRNAs have become a new research hotspot in the field of tumor pathology. In the present study, the current understanding of the biogenesis, characteristics, databases, research methods, biological functions subcellular distribution, epigenetic regulation, extracellular transport and degradation of circRNAs was discussed. In particular, the multiple databases and methods involved in circRNA research were first summarized, and the recent advances in determining the potential roles of circRNAs in tumor growth, migration and invasion, which render circRNAs better predictive biomarkers, were described. Furthermore, future perspectives for the clinical application of circRNAs in the management of patients with cancer were proposed, which could provide new insights into circRNAs in the future.
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Key Words
- AML, acute myloid leukemia
- BSJ, back-splice junction
- Biomarker
- CLL, chronic lymphocytic leukemia
- CML, chronic myeloid leukemia
- CRC, colorectal cancer
- Cancer
- Circular RNAs
- EIciRNAs, exon–intron RNAs
- EMT, epithelial-mesenchymal transition
- Functions
- GC, gastric cancer
- HCC, hepatocellular carcinoma
- ISH, in situ hybridization
- LUAD, lung adenocarcinoma
- MER, miRNA response elements
- MM, multiple myeloma
- NSCLC, non-small cell lung cancer
- PCR, polymerase chain reaction
- PDAC, pancreatic ductal adenocarcinoma
- RBP, RNA-binding protein
- RNA, ribonucleic acid
- RNase, ribonuclease
- RT-PCR, reverse transcription-PCR
- TNM, tumor node metastases
- UTR, untranslated regions
- ccRCC, clear cell renal cell carcinoma
- ceRNAs, endogenous RNAs
- ciRNAs, circular intronic RNAs
- ciRS-7, circular RNA sponge for miR-7
- circRNAs, circular RNAs
- ecircRNAs, exonic circular RNAs
- lncRNAs, long ncRNA
- miRNAs, microRNAs
- ncRNAs, noncoding RNAs
- qPCR, quantitative PCR
- rRNA, ribosomal RNA
- siRNAs, small interfering RNAs
- snRNA, small nuclear RNA
- tricRNAs, tRNA intronic circRNAs
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Affiliation(s)
- Xiaozhu Tang
- The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Hongyan Ren
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Mengjie Guo
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jinjun Qian
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Ye Yang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Chunyan Gu
- The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, China
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
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Cheng D, Wang J, Dong Z, Li X. Cancer-related circular RNA: diverse biological functions. Cancer Cell Int 2021; 21:11. [PMID: 33407501 PMCID: PMC7789196 DOI: 10.1186/s12935-020-01703-z] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 12/04/2020] [Indexed: 02/06/2023] Open
Abstract
Noncoding RNAs, including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in regulating biological functions. In recent decades, miRNAs and lncRNAs have both inspired a wave of research, but the study of circRNA functions is still in its infancy. Studies have found that circRNAs actively participate in the occurrence and development of various diseases, which emphasizes the importance of circRNAs. Here, we review the features and classification of circRNAs and summarize their functions. Then, we briefly describe how to analyze circRNAs by bioinformatics procedures. In addition, the relationship between circRNAs and cancers is discussed with an emphasis on proving whether circRNAs can be potential biomarkers for the prognosis and diagnosis of cancer.
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Affiliation(s)
- Dan Cheng
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China
| | - Jing Wang
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China
| | - Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China.,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China
| | - Xiang Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. .,China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China.
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Chen X, Sun H, Zhao Y, Zhang J, Xiong G, Cui Y, Lei C. CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis. Open Med (Wars) 2021; 16:104-116. [PMID: 33506107 PMCID: PMC7801883 DOI: 10.1515/med-2021-0001] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 10/29/2020] [Accepted: 10/30/2020] [Indexed: 02/06/2023] Open
Abstract
Background The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC. Methods The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities. Conclusion Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.
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Affiliation(s)
- Xiaobo Chen
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
| | - Hongwen Sun
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
| | - Yunping Zhao
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
| | - Jing Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
| | - Guosheng Xiong
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
| | - Yue Cui
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
| | - Changcheng Lei
- Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China
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Wang M, Gong Z, Zhao X, Yu W, Huang F, Dong H. Circular RNAs emerge as important regulators with great potential for clinical application in gastric cancer. Biomark Med 2021; 15:69-82. [PMID: 33185463 DOI: 10.2217/bmm-2020-0591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 10/28/2020] [Indexed: 01/17/2023] Open
Abstract
Gastric cancer (GC) is a common digestive malignancy with a high-ranking morbidity and mortality. Therefore, it is urgent to identify novel indicators and develop new strategies for clinical diagnosis and treatment of GC. As a type of noncoding RNA, circular RNAs (circRNAs) have received increased attention in GC during recent years. To more comprehensively understand current research progress on circRNAs in GC, in this review, we introduce basic knowledge of circRNAs, summarize abnormally expressed circRNAs and discuss their functions and regulatory molecular mechanisms in GC. Then, we review potential applications of circRNAs for GC diagnosis, prognosis and treatment. Finally, we conclude by highlighting major advancements of circRNAs in GC research, and we discuss existing challenges and possible future research directions of GC-associated circRNAs.
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Affiliation(s)
- Mei Wang
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Zheng Gong
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Xinxin Zhao
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Wanjun Yu
- Key Laboratory of Medical Science & Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212013, China
| | - Feng Huang
- Department of Clinical Laboratory, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Suzhou, Jiangsu Province 215300, China
| | - Haibo Dong
- Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Gulou District, Nanjing, Jiangsu Province 210008, China
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Guan Y, Zhang Y, Hao L, Nie Z. CircRNA_102272 Promotes Cisplatin-Resistance in Hepatocellular Carcinoma by Decreasing MiR-326 Targeting of RUNX2. Cancer Manag Res 2020; 12:12527-12534. [PMID: 33324096 PMCID: PMC7732977 DOI: 10.2147/cmar.s258230] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/30/2020] [Indexed: 12/22/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the leading cause of tumor-associated death in males and females worldwide. HCC is mostly diagnosed at advanced stages and the chemotherapeutic cisplatin is one of the major therapeutic options in the treatment of patients with treating advanced HCC. Despite several reports on HCC multidrug resistance, the underlying regulatory mechanisms are still unclear. Methods RT-PCR was performed to detect circRNA_102272, miR-326 and RUNX2 expression. The CCK8 assay was used to examine cell proliferation and cisplatin IC50 values. The luciferase reporter assay was performed to verify complementary combinations between circRNA_102272 and miR-326 and between miR-326 and RUNX2. Results CircRNA_102272 expression was upregulated in HCC tissues and cells. CircRNA_102272 knockdown suppressed HCC cell proliferation and decreased cisplatin-resistance. In addition, circRNA_102272 facilitated HCC cisplatin-resistance by regulating the miR-326/RUNX2 axis. Conclusion CircRNA_102272 is significantly increased in HCC tissues and cells and promotes HCC cell proliferation and cisplatin-resistance. More importantly, circRNA acts as a ceRNA to suppress the expression and activity of miR-326, leading to the increase in RUNX2 expression. By elucidating circRNA_102272 role and mechanism of action in HCC, our study provides insights and an opportunity to overcome cisplatin-resistance in HCC.
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Affiliation(s)
- Yonghai Guan
- Department of Infectious Diseases, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, People's Republic of China
| | - Ying Zhang
- Sixth Department of Liver Diseases, The Sixth People's Hospital of Dalian, Dalian Medical University, Dalian 116031, Liaoning, People's Republic of China
| | - Lina Hao
- Department of Nephrology, The Third People's Hospital of Dalian, Dalian 116000, Liaoning, People's Republic of China
| | - Zhenwang Nie
- Department of Infectious Diseases, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, People's Republic of China
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Rajappa A, Banerjee S, Sharma V, Khandelia P. Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics. Front Mol Biosci 2020; 7:577938. [PMID: 33195421 PMCID: PMC7655967 DOI: 10.3389/fmolb.2020.577938] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/26/2020] [Indexed: 12/17/2022] Open
Abstract
Circular RNAs (circRNAs) are rapidly coming to the fore as major regulators of gene expression and cellular functions. They elicit their influence via a plethora of diverse molecular mechanisms. It is not surprising that aberrant circRNA expression is common in cancers and they have been implicated in multiple aspects of cancer pathophysiology such as apoptosis, invasion, migration, and proliferation. We summarize the emerging role of circRNAs as biomarkers and therapeutic targets in cancer.
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Affiliation(s)
| | | | - Vivek Sharma
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad, India
| | - Piyush Khandelia
- Department of Biological Sciences, Birla Institute of Technology and Science, Pilani - Hyderabad Campus, Hyderabad, India
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