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Zhang Y, Wang B, Chen J, Li T. Role of exosomal miRNAs and macrophage polarization in gastric cancer: A novel therapeutic strategy. Eur J Pharmacol 2025; 990:177268. [PMID: 39805486 DOI: 10.1016/j.ejphar.2025.177268] [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: 10/04/2024] [Revised: 01/09/2025] [Accepted: 01/09/2025] [Indexed: 01/16/2025]
Abstract
Gastric cancer (GC) is one of the most common gastrointestinal cancers worldwide, with consistently high morbidity and mortality rates and poor prognosis. Most patients are diagnosed at an advanced stage due to the lack of specific presentation in the early stages. Exosomes are a class of extracellular vesicles (EVs) widely found in body fluids and can release genetic material or multiple proteins to facilitate intercellular communication. In recent years, exosomal miRNAs have gained attention for their role in various cancers. These exosomal miRNAs can impact GC development and progression by targeting specific genes or influencing signaling pathways and cytokines involved in Angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and immune regulation. They show great potential in terms of diagnosis, prognosis, and treatment of GC. Notably, the gastrointestinal tract has the largest number of macrophages, which play a significant role in GC progression. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) and can influence macrophage programming through various mediators, including macrophage polarization. Macrophage polarization is involved in inflammatory responses and significantly impacts the GC process.
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Affiliation(s)
- Yun Zhang
- School of Clinical Medicine, Ningxia Medical University, Ningxia, China; General Hospital of Ningxia Medical University, Ningxia, China
| | - Baozhen Wang
- School of Clinical Medicine, Ningxia Medical University, Ningxia, China; General Hospital of Ningxia Medical University, Ningxia, China
| | - Jing Chen
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
| | - Tao Li
- Department of Surgical Oncology, Tumor Hospital, The General Hospital of Ningxia Medical University, Ningxia, China.
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2
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Dana F, Mahjoub S, Shokati Eshkiki Z, Namazi A, Tabaeian SP, Akbari A. Clinical relevance of plasma-derived exosomal long non-coding RNAs (lncRNAs) CCAT1 and XIST in colorectal cancer patients. MOLECULAR BIOLOGY RESEARCH COMMUNICATIONS 2025; 14:157-166. [PMID: 40028475 PMCID: PMC11865934 DOI: 10.22099/mbrc.2025.51654.2061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
The expression level of exosomal long non-coding RNAs (lncRNAs) can be relevant for clinical diagnostic approaches. The object of our study was to evaluate the differential expression of lncRNAs colon cancer associated transcript 1 (CCAT1) and X-inactive specific transcript (XIST) in plasma exosomes of colorectal cancer (CRC) patients and investigate their potential as clinical biomarkers. In a case-control study, 62 CRC patients and 62 healthy persons were studied. Plasma exosomes were isolated by a centrifugation approach and were characterized by microscopy and western blotting. After RNA extraction and cDNA synthesis, using real-time PCR technique, the relative expression of lncRNAs was evaluated. The expression levels of lncRNA CCAT1, but not XIST, were meaningfully increased in the plasma-derived exosomes of CRC patients compared to non-cancer individuals (p= 0.001, 0.083 respectively). Further analyses revealed that the expression levels of exosomal lncRNA CCAT1 were associated with the lymphovascular invasion and tumor differentiation (p<0.05). ROC curve analysis documented a diagnostic power for lncRNA CCAT1 in CRC with a sensitivity of 79% and a specificity of 80% with an optimal cutoff point 6.5, with an area under curve (AUC)=86% and p<0.0001. Also, lncRNA XIST revealed a sensitivity of 62% and a specificity of 61% with a cutoff point 2.4, with an AUC=65%. Our findings indicated the potential of plasma-derived exosomal lncRNA CCAT1 as a non-invasive clinical indicator for the diagnosis of CRC patients.
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Affiliation(s)
- Fatemeh Dana
- Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Soleiman Mahjoub
- Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Zahra Shokati Eshkiki
- Alimentary Tract Research Center, Clinical Sciences Research Institute, Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abolfazl Namazi
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Seidamir Pasha Tabaeian
- Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
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Raval H, Bhattacharya S. Early Detection, Precision Treatment, Recurrence Monitoring: Liquid Biopsy Transforms Colorectal Cancer Therapy. Curr Cancer Drug Targets 2025; 25:586-619. [PMID: 38623975 DOI: 10.2174/0115680096295070240318075023] [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: 11/26/2023] [Revised: 02/13/2024] [Accepted: 02/21/2024] [Indexed: 04/17/2024]
Abstract
Colorectal cancer (CRC) is a significant global health concern. We need ways to detect it early and determine the best treatments. One promising method is liquid biopsy, which uses cancer cells and other components in the blood to help diagnose and treat the disease. Liquid biopsies focus on three key elements: circulating tumor DNA (ctDNA), circulating microRNA (miRNA), and circulating tumor cells (CTC). By analyzing these elements, we can identify CRC in its early stages, predict how well a treatment will work, and even spot signs of cancer returning. This study investigates the world of liquid biopsy, a rapidly growing field. We want to understand how it can help us better recognize the molecular aspects of cancer, improve and diagnostics, tailor treatments to individual patients, and keep track of the disease over the long-term. We explored specific components of liquid biopsy, like extracellular vesicles and cell-free DNA, and how they are used to detect CRC. This review sheds light on the current state of knowledge and the many ways a liquid biopsy can be used in treating colorectal cancer. It can transform patient care, disease management, and clinical outcomes by offering non-invasive cancer-targeting solutions.
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Affiliation(s)
- Harshvardhan Raval
- Department of Pharmaceutics, School of Pharmacy and Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India
| | - Sankha Bhattacharya
- Department of Pharmaceutics, School of Pharmacy and Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India
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4
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Hu B, Zhang Y, Jiang B, Li A. Prognostic value of circulating long non-coding RNAs in colorectal cancer patients: a meta-analysis. Expert Rev Anticancer Ther 2024; 24:1249-1259. [PMID: 37934874 DOI: 10.1080/14737140.2023.2280643] [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: 11/01/2022] [Accepted: 10/27/2023] [Indexed: 11/09/2023]
Abstract
OBJECTIVES This meta-analysis aimed to evaluate the prognostic significance of circulating long non-coding RNAs (lncRNAs) in colorectal cancer (CRC). METHODS A comprehensive literature search was conducted in databases (Embase, Web of Science, PubMed, and Cochrane Library) up to July 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed with Review Manager 5.4 and Stata 17.0. Publication bias was assessed using Begg's test, and sensitivity analysis was conducted to validate the meta-analysis results. RESULTS Ten articles, comprising 1,473 CRC patients and 18 different circulating lncRNAs, were included. Thirteen circulating lncRNAs were found to be up-regulated in CRC patients, while five were down-regulated. High expression of circulating lncRNAs up-regulated in CRC patients was associated with shorter CRC OS (HR = 2.91, 95% CI: 1.17, 7.22; P = 0.02, I2 = 86%). Conversely, high expression of circulating lncRNAs down-regulated in CRC patients was linked to longer CRC OS (HR = 0.16, 95% CI: 0.07, 0.40; P < 0.0001, I2 = 0%) and improved DFS (HR = 0.52, 95% CI: 0.37, 0.74; P = 0.0002, I2 = 0%). Additionally, circulating lncRNA levels correlated with TNM staging, tumor location, and lymph node metastasis. CONCLUSION Circulating lncRNAs show promise as prognostic markers for CRC patients, but further studies are warranted to validate these findings.
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Affiliation(s)
- Bin Hu
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Yanfei Zhang
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Bingjing Jiang
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
| | - Angcheng Li
- Department of Pathology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua City, Zhejiang Province, China
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5
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Tang H, Liu X, Ke J, Tang Y, Luo S, Li XK, Huang M. New perspectives of exosomes in urologic malignancies - Mainly focus on biomarkers and tumor microenvironment. Pathol Res Pract 2024; 263:155645. [PMID: 39476607 DOI: 10.1016/j.prp.2024.155645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 08/09/2024] [Accepted: 10/02/2024] [Indexed: 11/10/2024]
Abstract
Bladder cancer (BCa) and renal cell carcinoma (RCC) are prevalent urologic malignancies (UM) characterized by high morbidity and frequent recurrence. Current diagnostic approaches, often invasive, often indicate an advanced disease stage. And the complex tumor microenvironment often promotes tumor progression and induces resistance to chemotherapy. Current diagnostic and therapeutic modalities often fail to achieve satisfactory outcomes for patients. Exosomes transport diverse cargoes, including cytokines, proteins, lipids, non-coding RNAs, and microRNAs, crucial for intercellular communication. Exosomes have shown potential as biomarkers for UM, participating in tumor progression, especially within the tumor microenvironment (TME), including tumor cell apoptosis, proliferation, migration, invasion, depletion of immune cell function, epithelial-mesenchymal transition (EMT), angiogenesis, and more.In this review, we summarize research advances related to exosomes in UM, focusing on the role of exosomes as biomarkers in bladder and renal cancer, highlighting their significance within the TME.
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Affiliation(s)
- Hai Tang
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xing Liu
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Jingwei Ke
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yiquan Tang
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Songtao Luo
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Xu Kun Li
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Mingwei Huang
- Urology department, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
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Luo S, Yue M, Wang D, Lu Y, Wu Q, Jiang J. Breaking the barrier: Epigenetic strategies to combat platinum resistance in colorectal cancer. Drug Resist Updat 2024; 77:101152. [PMID: 39369466 DOI: 10.1016/j.drup.2024.101152] [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: 05/22/2024] [Revised: 08/22/2024] [Accepted: 09/20/2024] [Indexed: 10/08/2024]
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Platinum-based drugs, such as cisplatin and oxaliplatin, are frontline chemotherapy for CRC, effective in both monotherapy and combination regimens. However, the clinical efficacy of these treatments is often undermined by the development of drug resistance, a significant obstacle in cancer therapy. In recent years, epigenetic alterations have been recognized as key players in the acquisition of resistance to platinum drugs. Targeting these dysregulated epigenetic mechanisms with small molecules represents a promising therapeutic strategy. This review explores the complex relationship between epigenetic changes and platinum resistance in CRC, highlighting current epigenetic therapies and their effectiveness in countering resistance mechanisms. By elucidating the epigenetic underpinnings of platinum resistance, this review aims to contribute to ongoing efforts to improve treatment outcomes for CRC patients.
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Affiliation(s)
- Shiwen Luo
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Ming Yue
- Department of Pharmacy, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
| | - Dequan Wang
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Yukang Lu
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China
| | - Qingming Wu
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China; Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan 430065, China.
| | - Jue Jiang
- Institute of Infection, Immunology and Tumor Microenvironment, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China.
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7
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Zhu M, Gao Y, Zhu K, Yuan Y, Bai H, Meng L. Exosomal miRNA as biomarker in cancer diagnosis and prognosis: A review. Medicine (Baltimore) 2024; 103:e40082. [PMID: 39432619 PMCID: PMC11495718 DOI: 10.1097/md.0000000000040082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 09/26/2024] [Indexed: 10/23/2024] Open
Abstract
Exosomes, which are extracellular vesicles with a diameter ranging from 40 to 160 nm, are abundantly present in various body fluids. Exosomal microRNA (ex-miR), due to its exceptional sensitivity and specificity, has garnered significant attention. Notably, ex-miR is consistently detected in almost all bodily fluids, highlighting its potential as a reliable biomarker. This attribute of ex-miR has piqued considerable interest in its application as a diagnostic tool for the early detection, continuous monitoring, and prognosis evaluation of cancer. Given the critical role of exosomes and their cargo in cancer biology, this review explores the intricate processes of exosome biogenesis and uptake, their multifaceted roles in cancer development and progression, and the potential of ex-miRs as biomarkers for tumor diagnosis and prognosis.
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Affiliation(s)
- Mingliao Zhu
- Medical School of Shaoxing University, Yuecheng, Shaoxing, Zhejiang Province, People’s Republic of China
| | - Yuan Gao
- Department of Breast and Thyroid Surgery, Shaoxing People’s Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, People’s Republic of China
| | - Kaijun Zhu
- Medical School of Shaoxing University, Yuecheng, Shaoxing, Zhejiang Province, People’s Republic of China
| | - Ying Yuan
- Medical School of Shaoxing University, Yuecheng, Shaoxing, Zhejiang Province, People’s Republic of China
| | - Haoyang Bai
- Medical School of Shaoxing University, Yuecheng, Shaoxing, Zhejiang Province, People’s Republic of China
| | - Liwei Meng
- Department of Breast and Thyroid Surgery, Shaoxing People’s Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, People’s Republic of China
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8
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Wei C, Zhang C, Zhou Y, Wang J, Jin Y. Progress of Exosomal LncRNAs in Pancreatic Cancer. Int J Mol Sci 2024; 25:8665. [PMID: 39201351 PMCID: PMC11354448 DOI: 10.3390/ijms25168665] [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: 06/30/2024] [Revised: 07/27/2024] [Accepted: 07/28/2024] [Indexed: 09/02/2024] Open
Abstract
Pancreatic cancer is a prevalent malignant tumor with rising medication resistance and mortality. Due to a dearth of specific and trustworthy biomarkers and therapeutic targets, pancreatic cancer early detection and treatment are still not at their best. Exosomal LncRNAs have been found to be plentiful and persistent within exosomes, and they are capable of functioning whether the exosomes are traveling to close or distant cells. Furthermore, increasing evidence suggests that exosomal LncRNA, identified as an oncogene or tumor suppressor-control the growth, metastasis, and susceptibility of pancreatic cancer to chemotherapy and radiation therapy. Promising prospects for both antitumor targets and diagnostic biomarkers are exosomal LncRNAs. The primary features of exosomal LncRNAs, their biological roles in the onset and progression of pancreatic cancer, and their potential as therapeutic targets and diagnostic molecular markers are outlined in this review.
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Affiliation(s)
| | | | | | | | - Yong Jin
- School of Pharmacy, Anhui Medical University, Hefei 230032, China
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9
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Ryu H, Kim JH, Kim YJ, Jeon H, Kim BC, Jeon Y, Kim Y, Bak H, Kang Y, Kim C, Um H, Ahn JH, Hyun H, Kim BC, Song I, Jeon S, Bhak J, Han EC. Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer. Clin Epigenetics 2024; 16:95. [PMID: 39030645 PMCID: PMC11264732 DOI: 10.1186/s13148-024-01708-9] [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: 12/26/2023] [Accepted: 07/09/2024] [Indexed: 07/21/2024] Open
Abstract
BACKGROUND Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. RESULTS We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. CONCLUSIONS This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.
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Affiliation(s)
- Hyojung Ryu
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | - Ji-Hoon Kim
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
- GenomeLab, Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea
- Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea
| | - Yeo Jin Kim
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | - Hahyeon Jeon
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | | | - Yeonsu Jeon
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | | | - Hyebin Bak
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | | | - Changjae Kim
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | - Hyojin Um
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | - Ji-Hye Ahn
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | - Hwi Hyun
- Clinomics, Inc., Ulsan, 44919, Republic of Korea
| | | | - Inho Song
- Division of Colorectal Surgery, Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, 46033, Republic of Korea
| | - Sungwon Jeon
- Clinomics, Inc., Ulsan, 44919, Republic of Korea.
- Geromics Inc., Suwon, 16229, Republic of Korea.
| | - Jong Bhak
- Clinomics, Inc., Ulsan, 44919, Republic of Korea.
- GenomeLab, Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
- Department of Biomedical Engineering, College of Information and Biotechnology, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
- Geromics Inc., Suwon, 16229, Republic of Korea.
- Personal Genomics Institute (PGI), Genome Research Foundation (GRF), Cheongju, 28160, Republic of Korea.
| | - Eon Chul Han
- Division of Colorectal Surgery, Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, 46033, Republic of Korea.
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10
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Xin GD, Liu XY, Fan XD, Zhao GJ. Exosomes repairment for sciatic nerve injury: a cell-free therapy. Stem Cell Res Ther 2024; 15:214. [PMID: 39020385 PMCID: PMC11256477 DOI: 10.1186/s13287-024-03837-7] [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: 05/28/2024] [Accepted: 07/05/2024] [Indexed: 07/19/2024] Open
Abstract
Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient's quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.
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Affiliation(s)
- Guang-Da Xin
- Nephrology Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130000, China
| | - Xue-Yan Liu
- Cardiology Department, China-Japan Union Hospital of Jilin Universit, Changchun, Jilin Province, 130000, China
| | - Xiao-Di Fan
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130000, China
| | - Guan-Jie Zhao
- Nephrology Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130000, China.
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11
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Li Y, Tang X, Deng R, Feng L, Xie S, Chen M, Zheng J, Chang K. Dumbbell Dual-Hairpin Triggered DNA Nanonet Assembly for Cascade-Amplified Sensing of Exosomal MicroRNA. ACS OMEGA 2024; 9:19723-19731. [PMID: 38708273 PMCID: PMC11064005 DOI: 10.1021/acsomega.4c02652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 04/07/2024] [Accepted: 04/10/2024] [Indexed: 05/07/2024]
Abstract
Exosomal microRNAs (miRNAs) are valuable biomarkers closely associated with cancer progression. Therefore, sensitive and specific exosomal miRNA biosensing has been employed for cancer diagnosis, prognosis, and prediction. In this study, a miRNA-based DNA nanonet assembly strategy is proposed, enabling the biosensing of exosomal miRNAs through dumbbell dual-hairpin under isothermal enzyme-free conditions. This strategy dexterously designs a specific dumbbell dual-hairpin that can selectively recognize exosomal miRNA, inducing conformational changes to cascade-generated X-shaped DNA structures, facilitating the extension of the X-shaped DNA in three-dimensional space, ultimately forming a DNA nanonet assembly. On the basis of the target miRNA, our design enriches the fluorescence signal through the cascade assembly of DNA nanonet and realizes the secondary signal amplification. Using exosomal miR-141 as the target, the resultant fluorescence sensing demonstrates an impressive detection limit of 57.6 pM and could identify miRNA sequences with single-base variants with high specificity. Through the analysis of plasma and urine samples, this method effectively distinguishes between benign prostatic hyperplasia, prostate cancer, and metastatic prostate cancer. Serving as a novel noninvasive and accurate screening and diagnostic tool for prostate cancer, this dumbbell dual-hairpin triggered DNA nanonet assembly strategy is promising for clinical applications.
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Affiliation(s)
- Yongxing Li
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
- Department
of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), 183 Xinqiao, Shapingba
District, Chongqing 400037, P. R. China
- School
of Medicine, Chongqing University, Chongqing 400030, P. R. China
| | - Xiaoqi Tang
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
| | - Ruijia Deng
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
| | - Liu Feng
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
| | - Shuang Xie
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
| | - Ming Chen
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
| | - Ji Zheng
- Department
of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), 183 Xinqiao, Shapingba
District, Chongqing 400037, P. R. China
- School
of Medicine, Chongqing University, Chongqing 400030, P. R. China
| | - Kai Chang
- Department
of Clinical Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan, Shapingba
District, Chongqing 400038, P. R. China
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12
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Yu T, Yang LL, Zhou Y, Wu MF, Jiao JH. Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy. Stem Cell Res Ther 2024; 15:6. [PMID: 38167108 PMCID: PMC10763489 DOI: 10.1186/s13287-023-03614-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 12/12/2023] [Indexed: 01/05/2024] Open
Abstract
Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30-150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.
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Affiliation(s)
- Tong Yu
- Department of Orthopedic, The Second Norman Bethune Hospital of Jilin University, Changchun, 130000, Jilin Province, China
| | - Li-Li Yang
- Department of Orthopedic, The Second Norman Bethune Hospital of Jilin University, Changchun, 130000, Jilin Province, China
| | - Ying Zhou
- Department of Operating Room, The Third Hospital of Qinhuangdao, Qinhuangdao, 066000, Hebei Province, China
| | - Min-Fei Wu
- Department of Orthopedic, The Second Norman Bethune Hospital of Jilin University, Changchun, 130000, Jilin Province, China
| | - Jian-Hang Jiao
- Department of Orthopedic, The Second Norman Bethune Hospital of Jilin University, Changchun, 130000, Jilin Province, China.
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13
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Bagheri R, Ghorbian M, Ghorbian S. Tumor circulating biomarkers in colorectal cancer. Cancer Treat Res Commun 2023; 38:100787. [PMID: 38194840 DOI: 10.1016/j.ctarc.2023.100787] [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: 11/03/2023] [Revised: 12/11/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024]
Abstract
CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.
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Affiliation(s)
- Raana Bagheri
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Mohsen Ghorbian
- Department of Computer Engineering, Qom Branch, Islamic Azad University, Qom, Iran
| | - Saeid Ghorbian
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran.
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14
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Wu Z, Yu X, Zhang S, He Y, Guo W. Novel roles of PIWI proteins and PIWI-interacting RNAs in human health and diseases. Cell Commun Signal 2023; 21:343. [PMID: 38031146 PMCID: PMC10685540 DOI: 10.1186/s12964-023-01368-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/26/2023] [Indexed: 12/01/2023] Open
Abstract
Non-coding RNA has aroused great research interest recently, they play a wide range of biological functions, such as regulating cell cycle, cell proliferation, and intracellular substance metabolism. Piwi-interacting RNAs (piRNAs) are emerging small non-coding RNAs that are 24-31 nucleotides in length. Previous studies on piRNAs were mainly limited to evaluating the binding to the PIWI protein family to play the biological role. However, recent studies have shed more lights on piRNA functions; aberrant piRNAs play unique roles in many human diseases, including diverse lethal cancers. Therefore, understanding the mechanism of piRNAs expression and the specific functional roles of piRNAs in human diseases is crucial for developing its clinical applications. Presently, research on piRNAs mainly focuses on their cancer-specific functions but lacks investigation of their expressions and epigenetic modifications. This review discusses piRNA's biogenesis and functional roles and the recent progress of functions of piRNA/PIWI protein complexes in human diseases. Video Abstract.
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Affiliation(s)
- Zeyu Wu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, 450052, China
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, 450052, China
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, 450052, China
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, 450052, China.
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China.
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, 450052, China.
- Henan Key Laboratory of Digestive Organ Transplantation, Zhengzhou, 450052, China.
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15
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ZHANG YUN, TANG SHALING, GAO YUBO, LU ZHONGTING, YANG YUAN, CHEN JING, LI TAO. Application of exosomal miRNA mediated macrophage polarization in colorectal cancer: Current progress and challenges. Oncol Res 2023; 32:61-71. [PMID: 38188683 PMCID: PMC10767244 DOI: 10.32604/or.2023.043481] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 09/06/2023] [Indexed: 01/09/2024] Open
Abstract
Colorectal cancer (CRC) is a major global health problem with high morbidity and mortality rates. Surgical resection is the main treatment for early-stage CRC, but detecting it early is challenging. Therefore, effective therapeutic targets for advanced patients are still lacking. Exosomes, tiny vesicles in body fluids, play a crucial role in tumor metastasis, immune regulation, and drug resistance. Interestingly, they can even serve as a biomarker for cancer diagnosis and prognosis. Studies have shown that exosomes can carry miRNA, mediate the polarization of M1/M2 macrophages, promote the proliferation and metastasis of cancer cells, and affect the prognosis of CRC. Since the gastrointestinal tract has many macrophages, understanding the mechanism behind exosomal miRNA-mediated macrophage polarization in CRC treatment is crucial. This article summarizes recent advancements in the study of exosomal miRNAs in CRC and their potential as diagnostic and prognostic markers.
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Affiliation(s)
- YUN ZHANG
- Department of Oncology, School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - SHALING TANG
- Department of Oncology, School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - YUBO GAO
- Department of Oncology, School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - ZHONGTING LU
- Department of Oncology, School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - YUAN YANG
- Department of Oncology, School of Clinical Medicine, Ningxia Medical University, Yinchuan, China
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - JING CHEN
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China
| | - TAO LI
- Department of Surgical Oncology, Tumor Hospital, The General Hospital of Ningxia Medical University, Yinchuan, China
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16
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Gong Z, Wen M, Zhang W, Yu L, Huang C, Xu Y, Xia Z, Xu M, Xu J, Liang Q, Bao H, Cheng X. Plasma exosomes induce inflammatory immune response in patients with acute myocardial infarction. Arch Physiol Biochem 2023; 129:1168-1176. [PMID: 33950771 DOI: 10.1080/13813455.2021.1912102] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 01/07/2023]
Abstract
Exosomes are a kind of nanoscale extracellular vesicles with diameters of 30-100 nm and act as intracellular communication vehicles to influence cellular activities. Emerging pieces of evidence have indicated that exosomes play important roles in inflammation. However, the biological roles of plasma exosomes in acute myocardial infarction (AMI) patients have remained largely unexplored. In the current study, we found the plasma exosome levels were notably increased in patients with AMI in comparison with healthy controls (HCs), and AMI exosomes could induce endothelial cell injury. Furthermore, our data demonstrated that AMI exosomes triggered a pro-inflammatory immune response, at least partly depending on the activation of the NF-ĸB signalling. Together, AMI exosomes have pro-inflammatory properties and play a significant role in inflammation in AMI patients.
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Affiliation(s)
- Zhijian Gong
- Department of General Medicine, Ganzhou People's Hospital, Ganzhou, China
| | - Minghua Wen
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Weifang Zhang
- Department of Pharmacy, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Lingling Yu
- Department of Rehabilitation Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chahua Huang
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yan Xu
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zilong Xia
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Minxuan Xu
- Department of Cardiology, Ji'an Central Hospital, Ji'an, China
| | - Jianqing Xu
- Department of Cardiology, Union Shenzhen Hospital of Huazhong University of Science and Technology, Shenzhen, China
| | - Qian Liang
- Jiangxi Key Laboratory of Molecular Medicine, Nanchang, China
| | - Huihui Bao
- Department of General Medicine, Ganzhou People's Hospital, Ganzhou, China
| | - Xiaoshu Cheng
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
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17
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Zhang Y, Lu A, Zhuang Z, Zhang S, Liu S, Chen H, Yang X, Wang Z. Can Organoid Model Reveal a Key Role of Extracellular Vesicles in Tumors? A Comprehensive Review of the Literature. Int J Nanomedicine 2023; 18:5511-5527. [PMID: 37791321 PMCID: PMC10544113 DOI: 10.2147/ijn.s424737] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 09/19/2023] [Indexed: 10/05/2023] Open
Abstract
Extracellular vesicles (EVs) are small membrane-bound vesicles that are released by cells into the extracellular environment. The role of EVs in tumors has been extensively studied, and they have been shown to play a crucial role in tumor growth, progression, and metastasis. Past research has mainly used 2D-cultured cell line models to investigate the role of EVs in tumors, which poorly simulate the tumor microenvironment. Organoid technology has gradually matured in recent years. Organoids are similar in composition and behavior to physiological cells and have the potential to recapitulate the architecture and function of the original tissue. It has been widely used in organogenesis, drug screening, gene editing, precision medicine and other fields. The integration of EVs and organoids has the potential to revolutionize the field of cancer research and represents a promising avenue for advancing our understanding of cancer biology and the development of novel therapeutic strategies. Here, we aimed to present a comprehensive overview of studies using organoids to study EVs in tumors.
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Affiliation(s)
- Yang Zhang
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Anqing Lu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- Department of Central Transportation, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- West China School of Nursing, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Zixuan Zhuang
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Su Zhang
- Research Laboratory of Tumor Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease-Related Molecular Network and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Sicheng Liu
- Research Laboratory of Tumor Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease-Related Molecular Network and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Haining Chen
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Xuyang Yang
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
| | - Ziqiang Wang
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China
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18
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Hu R, Jahan MS, Tang L. ExoPD-L1: an assistant for tumor progression and potential diagnostic marker. Front Oncol 2023; 13:1194180. [PMID: 37736550 PMCID: PMC10509558 DOI: 10.3389/fonc.2023.1194180] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 08/11/2023] [Indexed: 09/23/2023] Open
Abstract
The proliferation and function of immune cells are often inhibited by the binding of programmed cell-death ligand 1 (PD-L1) to programmed cell-death 1 (PD-1). So far, many studies have shown that this combination poses significant difficulties for cancer treatment. Fortunately, PD-L1/PD-1 blocking therapy has achieved satisfactory results. Exosomes are tiny extracellular vesicle particles with a diameter of 40~160 nm, formed by cells through endocytosis. The exosomes are a natural shelter for many molecules and an important medium for information transmission. The contents of exosomes are composed of DNA, RNA, proteins and lipids etc. They are crucial to antigen presentation, tumor invasion, cell differentiation and migration. In addition to being present on the surface of tumor cells or in soluble form, PD-L1 is carried into the extracellular environment by tumor derived exosomes (TEX). At this time, the exosomes serve as a medium for communication between tumor cells and other cells or tissues and organs. In this review, we will cover the immunosuppressive role of exosomal PD-L1 (ExoPD-L1), ExoPD-L1 regulatory factors and emerging approaches for quantifying and detecting ExoPD-L1. More importantly, we will discuss how targeted ExoPD-L1 and combination therapy can be used to treat cancer more effectively.
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Affiliation(s)
- Rong Hu
- School of Life Sciences, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Md Shoykot Jahan
- School of Life Sciences, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
| | - Lijun Tang
- School of Life Sciences, Central South University, Changsha, China
- Xiangya School of Medicine, Central South University, Changsha, China
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19
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Bonilla CE, Montenegro P, O’Connor JM, Hernando-Requejo O, Aranda E, Pinto Llerena J, Llontop A, Gallardo Escobar J, Díaz Romero MDC, Bautista Hernández Y, Graña Suárez B, Batagelj EJ, Wali Mushtaq A, García-Foncillas J. Ibero-American Consensus Review and Incorporation of New Biomarkers for Clinical Practice in Colorectal Cancer. Cancers (Basel) 2023; 15:4373. [PMID: 37686649 PMCID: PMC10487247 DOI: 10.3390/cancers15174373] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/21/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
Advances in genomic technologies have significantly improved the management of colorectal cancer (CRC). Several biomarkers have been identified in CRC that enable personalization in the use of biologic agents that have shown to enhance the clinical outcomes of patients. However, technologies used for their determination generate massive amounts of information that can be difficult for the clinician to interpret and use adequately. Through several discussion meetings, a group of oncology experts from Spain and several Latin American countries reviewed the latest literature to provide practical recommendations on the determination of biomarkers in CRC based on their clinical experience. The article also describes the importance of looking for additional prognostic biomarkers and the use of histopathology to establish an adequate molecular classification. Present and future of immunotherapy biomarkers in CRC patients are also discussed, together with several techniques for marker determination, including liquid biopsy, next-generation sequencing (NGS), polymerase chain reaction (PCR), and fecal immunohistochemical tests. Finally, the role of Molecular Tumor Boards in the diagnosis and treatment of CRC is described. All of this information will allow us to highlight the importance of biomarker determination in CRC.
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Affiliation(s)
- Carlos Eduardo Bonilla
- Fundación CTIC—Centro de Tratamiento e Investigación sobre Cáncer, Bogotá 1681442, Colombia
| | - Paola Montenegro
- Institución AUNA OncoSalud e Instituto Nacional de Enfermedades Neoplásicas, Lima 15023, Peru
| | | | | | - Enrique Aranda
- Departamento de Oncología Médica, Hospital Reina Sofía, IMIBIC, UCO, CIBERONC, 14004 Cordoba, Spain;
| | | | - Alejandra Llontop
- Instituto de Oncología Ángel H. Roffo, Ciudad Autónoma de Buenos Aires C1437FBG, Argentina
| | | | | | | | - Begoña Graña Suárez
- Servicio de Oncología Médica, Hospital Universitario de A Coruña, Servicio Galego de Saúde (SERGAS), 15006 A Coruña, Spain;
| | | | | | - Jesús García-Foncillas
- Hospital Universitario Fundación Jiménez Díaz, Universidad Autónoma de Madrid, 28040 Madrid, Spain
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20
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Fang Q, Yuan Z, Hu H, Zhang W, Wang G, Wang X. Genome-wide discovery of circulating cell-free DNA methylation biomarkers for colorectal cancer detection. Clin Epigenetics 2023; 15:119. [PMID: 37501075 PMCID: PMC10375686 DOI: 10.1186/s13148-023-01518-5] [Citation(s) in RCA: 10] [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: 12/13/2022] [Accepted: 06/12/2023] [Indexed: 07/29/2023] Open
Abstract
BACKGROUND Colorectal polyp is known a precursor of colorectal cancer (CRC) that holds an increased risk for progression to CRC. Circulating cell-free DNA (cfDNA) methylation has shown favorable performance in the detection and monitoring the malignant progression in a variety of cancers. RESULTS To discover cfDNA methylation markers for the diagnosis of CRC, we first performed a genome-wide analysis between eight CRC and eight polyp tissues using the Infinium HumanMethylationEPIC BeadChip. We identified 7008 DMCs, and after filtering, we validated 39 DMCs by MethylTarget sequencing in 62 CRC and 56 polyp tissues. A panel of four CpGs (cg04486886, cg06712559, cg13539460, and cg27541454) was selected as the methylation marker in tissue by LASSO and random forest models. A diagnosis prediction model was built based on the four CpGs, and the methylation diagnosis score (md-score) can effectively discriminate tissues with CRC from polyp patients (AUROC > 0.9). Finally, the cg27541454 was confirmed hypermethylated in CRC (AUC = 0.85) in the plasma validation cohort. CONCLUSIONS Our findings suggest that the md-score could robustly detect CRC from polyp tissues, and cg27541454 may be a promising candidate noninvasive biomarker for CRC early diagnosis.
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Affiliation(s)
- Qingxiao Fang
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ziming Yuan
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Hanqing Hu
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Weiyuan Zhang
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Guiyu Wang
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
| | - Xishan Wang
- Colorectal Cancer Surgery Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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21
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Hu X, Lu Y, Zhou J, Wang L, Zhang M, Mao Y, Chen Z. Progress of regulatory RNA in small extracellular vesicles in colorectal cancer. Front Cell Dev Biol 2023; 11:1225965. [PMID: 37519298 PMCID: PMC10382209 DOI: 10.3389/fcell.2023.1225965] [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: 05/20/2023] [Accepted: 07/03/2023] [Indexed: 08/01/2023] Open
Abstract
Colorectal cancer (CRC) is the second most common malignant tumor of the gastrointestinal tract with the second highest mortality rate and the third highest incidence rate. Early diagnosis and treatment are important measures to reduce CRC mortality. Small extracellular vesicles (sEVs) have emerged as key mediators that facilitate communication between tumor cells and various other cells, playing a significant role in the growth, invasion, and metastasis of cancer cells. Regulatory RNAs have been identified as potential biomarkers for early diagnosis and prognosis of CRC, serving as crucial factors in promoting CRC cell proliferation, invasion and metastasis, angiogenesis, drug resistance, and immune cell differentiation. This review provides a comprehensive summary of the vital role of sEVs as biomarkers in CRC diagnosis and their potential application in CRC treatment, highlighting their importance as a promising avenue for further research and clinical translation.
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Affiliation(s)
- Xinyi Hu
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Yukang Lu
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Jiajun Zhou
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Lanfeng Wang
- Department of Nephrology, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Mengting Zhang
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Yiping Mao
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Zhiping Chen
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
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22
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Li X, Lin YL, Shao JK, Wu XJ, Li X, Yao H, Shi FL, Li LS, Zhang WG, Chang ZY, Chai NL, Wang YL, Linghu EQ. Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer. World J Gastroenterol 2023; 29:3482-3496. [PMID: 37389236 PMCID: PMC10303519 DOI: 10.3748/wjg.v29.i22.3482] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 05/04/2023] [Accepted: 05/11/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. AIM To identify a novel biomarker for early detection of GC. METHODS Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. RESULTS There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). CONCLUSION Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.
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Affiliation(s)
- Xiao Li
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Yan-Li Lin
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Jia-Kang Shao
- Medical School of Chinese PLA, Beijing 100853, China
| | - Xiao-Jie Wu
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Xiang Li
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - He Yao
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Fa-Liang Shi
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - Long-Song Li
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | - Wen-Gang Zhang
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
- Medical School of Chinese PLA, Beijing 100853, China
| | | | - Ning-Li Chai
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
| | - You-Liang Wang
- Beijing Institute of Biotechnology, Beijing 100071, China
| | - En-Qiang Linghu
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
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Li J, Bao Y, Peng S, Jiang C, Zhu L, Zou S, Xu J, Li Y. M2 Macrophages-Derived Exosomal miRNA-23a-3p Promotes the Progression of Oral Squamous Cell Carcinoma by Targeting PTEN. Curr Issues Mol Biol 2023; 45:4936-4947. [PMID: 37367063 DOI: 10.3390/cimb45060314] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/28/2023] Open
Abstract
Exosomes from tumor cells and immune cells regulate the tumor microenvironment through the biomolecules or microRNAs (miRNAs) they carry. This research aims to investigate the role of miRNA in exosomes derived from tumor-associated macrophages (TAMs) in the progression of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blotting assays were used to determine the expression of genes and proteins in OSCC cells. CCK-8, Scratch assay and invasion-related proteins were utilized to detect the malignant progression of tumor cells. High-throughput sequencing predicted differentially expressed miRNAs in exosomes secreted by M0 and M2 macrophages. Compared with exosomes from M0 macrophages, exosomes from M2 macrophages led to enhanced proliferation and invasion of OSCC cells and inhibited their apoptosis. High-throughput sequencing results show that miR-23a-3p is differentially expressed in exosomes from M0 and M2 macrophages. MiRNA target gene database predicts that phosphatase and tensin homolog (PTEN) are target genes of miR-23a-3p. Further studies revealed that transfection of miR-23a-3p mimics inhibited PTEN expression in vivo and in vitro and promoted the malignant progression of OSCC cells, which was reversed by miR-23a-3p inhibitors. MiR-23a-3p in exosomes derived from M2 macrophages promotes malignant progression of OSCC. PTEN is a potential intracellular target of miR-23a-3p. MiR-23a-3p, an M2 macrophage-associated exosome, is a promising target for the future treatment of OSCC.
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Affiliation(s)
- Jun Li
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Yongjie Bao
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Sisi Peng
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Chao Jiang
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Luying Zhu
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Sihai Zou
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Jie Xu
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
| | - Yong Li
- College of Stomatology, Chongqing Medical University, Chongqing 401147, China
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing 401147, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
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Luo Z, Ding E, Yu L, Wang W, Guo Q, Li X, Wang Y, Li T, Zhang Y, Zhang X. Identification of hub necroptosis-related lncRNAs for prognosis prediction of esophageal carcinoma. Aging (Albany NY) 2023; 15:204763. [PMID: 37263709 DOI: 10.18632/aging.204763] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 05/17/2023] [Indexed: 06/03/2023]
Abstract
Necroptosis is a newly identified programmed cell death associated with the biological process of various cancers, including esophageal carcinoma (ESCA). Meanwhile, the dysregulation of long non-coding RNAs (lncRNAs) is greatly implicated in ESCA progression and necroptosis regulation. However, the lncRNAs involved in regulating necroptosis in ESCA are still unclear. In this study, we aim to explore the expression profile of necroptosis-related lncRNAs (NRLs), and evaluate their roles in ESCA prognosis and treatment. In the present study, 198 differentially expressed NRLs were identified between the ESCA and adjacent normal tissues through screening the data extracted from the Cancer Genome Atlas (TCGA) database. And, a prognostic panel consisting of 6 NRLs was constructed using the LASSO algorithm and multivariate Cox regression analysis. The ESCA patients with high risks had a markedly reduced survival time and higher mortality prevalence. Moreover, C-index of 6 NRLs-panel was superior to 48 published prognostic models based on lncRNAs or mRNAs for ESCA. There were significant differences between the high-risk and low-risk groups in tumor-related pathways, genetic mutations, and drug sensitivity responses. In vitro analysis revealed that inhibition of PVT1 impeded the proliferation, migration, and colony formation of ESCA cells, increased the expressions of p-RIP1 and p-MLKL and promoted necroptosis. By contrast, PVT1 overexpression resulted in a decrease in necroptotic cell death events, thus promoting tumor progression. Collectively, the established 6-NRLs panel was a promising biomarker for the prognostic prediction of ESCA. Moreover, our current findings provided potential targets for individualized therapy for ESCA patients.
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Affiliation(s)
- Zhengdong Luo
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - E Ding
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Longchen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Wenwu Wang
- Hangzhou Lin’an District Fourth People’s Hospital, Hangzhou, Zhejiang Province, China
| | - Qining Guo
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Xinyang Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Yifeng Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Tingting Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China
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25
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Wu Z, Fang ZX, Hou YY, Wu BX, Deng Y, Wu HT, Liu J. Exosomes in metastasis of colorectal cancers: Friends or foes? World J Gastrointest Oncol 2023; 15:731-756. [PMID: 37275444 PMCID: PMC10237026 DOI: 10.4251/wjgo.v15.i5.731] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 03/07/2023] [Accepted: 04/04/2023] [Indexed: 05/12/2023] Open
Abstract
Colorectal cancer (CRC), the third most common type of cancer worldwide, threaten human health and quality of life. With multidisciplinary, including surgery, chemotherapy and/or radiotherapy, patients with an early diagnosis of CRC can have a good prognosis. However, metastasis in CRC patients is the main risk factor causing cancer-related death. To elucidate the underlying molecular mechanisms of CRC metastasis is the difficult and research focus on the investigation of the CRC mechanism. On the other hand, the tumor microenvironment (TME) has been confirmed as having an essential role in the tumorigenesis and metastasis of malignancies, including CRCs. Among the different factors in the TME, exosomes as extracellular vesicles, function as bridges in the communication between cancer cells and different components of the TME to promote the progression and metastasis of CRC. MicroRNAs packaged in exosomes can be derived from different sources and transported into the TME to perform oncogenic or tumor-suppressor roles accordingly. This article focuses on CRC exosomes and illustrates their role in regulating the metastasis of CRC, especially through the packaging of miRNAs, to evoke exosomes as novel biomarkers for their impact on the metastasis of CRC progression.
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Affiliation(s)
- Zheng Wu
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Ze-Xuan Fang
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yan-Yu Hou
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Bing-Xuan Wu
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu Deng
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Hua-Tao Wu
- Department of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jing Liu
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Li T, Zhou T, Wu J, Lv H, Zhou H, Du M, Zhang X, Wu N, Gong S, Ren Z, Zhang P, Zhang C, Liu G, Liu X, Zhang Y. Plasma exosome-derived circGAPVD1 as a potential diagnostic marker for colorectal cancer. Transl Oncol 2023; 31:101652. [PMID: 36934637 PMCID: PMC10034150 DOI: 10.1016/j.tranon.2023.101652] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 02/10/2023] [Accepted: 03/05/2023] [Indexed: 03/19/2023] Open
Abstract
BACKGROUND Although circular RNAs (circRNAs) have recently garnered interest as disease markers, they have been relatively poorly studied as a biomarker in colorectal cancer (CRC). In this study, we aimed to screen the exosome-derived circRNAs in CRC and explore their potential as diagnostic and prognostic biomarkers of CRC METHODS: Exosomes were extracted from the plasma using a kit and validated by immunoblotting, transmission electron microscopy, and particle size analysis. The microarray datasets were employed to identify differentially-expressed circRNAs from plasma exosomes. Real-time quantitative reverse transcription PCR (RT-qPCR) verified the results of the microarray analysis, and Receiver operating characteristic (ROC) curve revealed the diagnostic ability of a single circRNA. The Starbase combined with microT, miRmap, and RNA22 were used to establish a circRNA-miRNA-mRNA network. Gene ontology, Kyoto Encyclopedia of Genes, Genomes pathway enrichment analysis, and Gene Set Enrichment Analysis were applied to determine potential functions of the identified mRNAs RESULTS: Comparing the microarray of plasma exosome-derived circRNAs and the microarray downloaded from the GEO database, 15 candidate circRNAs with up-regulated expression were identified. RT-qPCR verified that hsa_circ_0003270 (circGAPVD1) was upregulated in CRC plasma exosomes. ROC analysis showed that circGAPVD1 in plasma exosomes has potential diagnostic value for CRC. The sensitivity and specificity of circGAPVD1 in the diagnosis of CRC were found to be 75.64 and 71.79%, respectively (area under ROC = 0.7662). Furthermore, the lymph node metastasis and TNM staging of patients were positively correlated with high expression of circGAPVD1. Combined with the ENCORI database and GEO datasets, we identified the circGAPVD1-related ceRNA network. The enrichment analysis revealed that key nodes in the ceRNA network participate in many important signaling pathways such as protein post-translational modifications CONCLUSION: Our results revealed the diagnostic efficiency of circGAPVD1 in plasma exosomes. The highly expressed circGAPVD1 is expected to be a novel diagnostic marker for CRC.
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Affiliation(s)
- Tiankang Li
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Tingting Zhou
- Department of Endocrinology, The Affiliated Hospital of China University of Mining and Technology, Xuzhou, China; Department of Endocrinology, Xuzhou first People's Hospital, Xuzhou, China
| | - Jin Wu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Heng Lv
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China
| | - Hui Zhou
- Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Mingnan Du
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xiuzhong Zhang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Nai Wu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Shuai Gong
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Zeqiang Ren
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Pengbo Zhang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Chong Zhang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Guangpu Liu
- Department of Spinal Surgery, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China
| | - Xin Liu
- Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China; Department of Endocrinology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
| | - Yi Zhang
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, China.
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Mezher M, Abdallah S, Ashekyan O, Shoukari AA, Choubassy H, Kurdi A, Temraz S, Nasr R. Insights on the Biomarker Potential of Exosomal Non-Coding RNAs in Colorectal Cancer: An In Silico Characterization of Related Exosomal lncRNA/circRNA–miRNA–Target Axis. Cells 2023; 12:cells12071081. [PMID: 37048155 PMCID: PMC10093117 DOI: 10.3390/cells12071081] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/28/2023] [Accepted: 03/31/2023] [Indexed: 04/07/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancer types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in the development of early detection strategies and preventive measures. Currently, components of bodily fluids, which may reflect various disease states, are being increasingly researched for their biomarker potential. One of these components is the circulating extracellular vesicles, namely, exosomes, which are demonstrated to carry various cargo. Of importance, the non-coding RNA cargo of circulating exosomes, especially long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs), may potentially serve as significant diagnostic and prognostic/predictive biomarkers. In this review, we present existing evidence on the diagnostic and prognostic/predictive biomarker value of exosomal non-coding RNAs in CRC. In addition, taking advantage of the miRNA sponging functionality of lncRNAs and circRNAs, we demonstrate an experimentally validated CRC exosomal non-coding RNA-regulated target gene axis benefiting from published miRNA sponging studies in CRC. Hence, we present a set of target genes and pathways downstream of the lncRNA/circRNA–miRNA–target axis along with associated significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may collectively serve to better characterize CRC and shed light on the significance of exosomal non-coding RNAs in CRC diagnosis and prognosis/prediction.
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Affiliation(s)
- Maria Mezher
- Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Samira Abdallah
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Ohanes Ashekyan
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Ayman Al Shoukari
- Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Hayat Choubassy
- Faculty of Sciences, Lebanese University, Beirut P.O. Box 6573, Lebanon
| | - Abdallah Kurdi
- Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Sally Temraz
- Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
| | - Rihab Nasr
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon
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28
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Hou MY, Liu YK. Progress in research of exosomal circRNAs in colorectal cancer. Shijie Huaren Xiaohua Zazhi 2023; 31:172-177. [DOI: 10.11569/wcjd.v31.i5.172] [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] [Indexed: 03/08/2023] Open
Abstract
Exosomes are lipid bilayer vesicles secreted by almost various cell types, including circRNAs, microRNAs (miRNAs), proteins, and nucleic acids. CircRNAs act as molecular sponges of miRNAs and participate in regulating gene transcription. This paper reviews the biogenesis, function, isolation, and identification of exosomal circRNAs and their role in the early diagnosis, prognosis, therapy, and drug resistance of colorectal cancer.
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Affiliation(s)
- Meng-Yuan Hou
- Graduate College of North China University of Technology, Tangshan 063200, Hebei Province, China
| | - Yan-Kun Liu
- Department of Medical Molecular Diagnosis, Tangshan People's Hospital, Tangshan Key Laboratory of Precision Medicine Testing, Tangshan 063000, Hebei Province, China
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Armakolas A, Kotsari M, Koskinas J. Liquid Biopsies, Novel Approaches and Future Directions. Cancers (Basel) 2023; 15:1579. [PMID: 36900369 PMCID: PMC10000663 DOI: 10.3390/cancers15051579] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 02/22/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
Cancer is among the leading causes of death worldwide. Early diagnosis and prognosis are vital to improve patients' outcomes. The gold standard of tumor characterization leading to tumor diagnosis and prognosis is tissue biopsy. Amongst the constraints of tissue biopsy collection is the sampling frequency and the incomplete representation of the entire tumor bulk. Liquid biopsy approaches, including the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs), as well as certain protein signatures that are released in the circulation from primary tumors and their metastatic sites, present a promising and more potent candidate for patient diagnosis and follow up monitoring. The minimally invasive nature of liquid biopsies, allowing frequent collection, can be used in the monitoring of therapy response in real time, allowing the development of novel approaches in the therapeutic management of cancer patients. In this review we will describe recent advances in the field of liquid biopsy markers focusing on their advantages and disadvantages.
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Affiliation(s)
- Athanasios Armakolas
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
- B' Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - Maria Kotsari
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 115 27 Athens, Greece
| | - John Koskinas
- B' Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece
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Zhang X, Hou H, Jiang M, Zhang X. Aberrant circulating tumor DNA methylation and exosomal microRNA biomarkers for early detection of colorectal cancer. Mol Biol Rep 2023; 50:2743-2750. [PMID: 36583782 DOI: 10.1007/s11033-022-08194-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 12/06/2022] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Colorectal cancer (CRC) became the third most commonly diagnosed malignancy and the second leading cause of cancer death in 2020. However, the rates of early screening and early diagnosis for CRC remain unsatisfactory. Thus, it is essential to explore the initiating factors of CRC and strategies for its early diagnosis. Research progress in liquid biopsy has led to the finding that circulating tumor-derived DNA (ctDNA) and exosomes play vital roles in early detection of CRC. THE APPLICATIONS OF LIQUID BIOPSY FOR EARLY DETECTION OF COLORECTAL CANCER: Moreover, the increased understanding of epigenetics has highlighted the role of ctDNA methylation in CRC carcinogenesis, and the detection of aberrant ctDNA methylation markers is a feasible strategy for diagnosis of early-stage CRC. Among exosomal markers, microRNAs (miRNAs) are abundant and are the most researched. Upregulated or downregulated expression of exosome-derived miRNAs can indicate the occurrence of early-stage CRC. FUTURE PERSPECTIVE The current research progress on aberrant ctDNA methylation and tumor exosomal miRNA biomarkers in early detection of CRC is summarized in this review, and the advantages and shortcomings of the methods are discussed.
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Affiliation(s)
- Xuchen Zhang
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Qingdao Cancer Institute, Qingdao University, Qingdao, China
| | - Helei Hou
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Qingdao Cancer Institute, Qingdao University, Qingdao, China
| | - Man Jiang
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China.,Qingdao Cancer Institute, Qingdao University, Qingdao, China
| | - Xiaochun Zhang
- Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China. .,Qingdao Cancer Institute, Qingdao University, Qingdao, China.
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31
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Zhang L, Shen Y, Wang Z, Li X, Xia W, Fan X, Su L, Wang D. Comprehensive analysis of exosomal circRNA, lncRNA, and mRNA profiles to identify the potential RNAs involved in the pathogenesis of venous malformation. J Oral Pathol Med 2023. [PMID: 36807323 DOI: 10.1111/jop.13416] [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: 10/22/2022] [Revised: 01/11/2023] [Accepted: 01/30/2023] [Indexed: 02/22/2023]
Abstract
BACKGROUND Venous malformation (VM) is a kind of congenital vascular anomaly with a high incidence of recurrence, detailed pathogenesis and standard treatment of VM still lack now. Increasing evidence showed exosomal RNA plays a pivotal role in various diseases. However, the underlying mechanism of VM based on the potential differentially exosomal RNAs remains unclear. METHODS Comparative high-throughput sequencing with serum exosomes from three VM patients and three healthy donors was used to explore differentially expressed (DE) circRNAs, DE lncRNAs, and DE mRNAs involving the formation of VM. We identified and verified DE circRNAs, DE lncRNAs, and DE mRNAs via qRT-PCR assay. We explored the potential functions of these exosomal DE non-coding RNAs via performing further Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Besides, circRNA/lncRNA-miRNA-mRNA linkages were also constructed to find their potential relationships in VM. RESULTS A total of 121 circRNAs, 53 lncRNAs, and 42 mRNAs (|log2 FC| ≥ 2.0, FDR <0.05, n = 3) were determined to be differentially expressed. QRT-PCR validated that these top-changed DE circRNAs, lncRNAs, and mRNAs had significant expression changes. Functional studies demonstrated that DE circRNAs play a pivotal role in thyroid hormone signaling pathway, DE lncRNAs function as a key regulator in MAPK signaling pathway and DE miRNAs participate in the process of hepatocellular carcinoma mostly. CONCLUSION Our study comprehensively depicted exosomal DE non-coding RNAs networks related to the pathogenesis of VM which can provide new insight into, a novel target for treating VM.
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Affiliation(s)
- Liming Zhang
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuchen Shen
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenfeng Wang
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiao Li
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiya Xia
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Xindong Fan
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lixin Su
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Fengcheng Hospital of Feng Xian District, Fengcheng Branch, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Deming Wang
- Vascular Anomaly Center, Department of Interventional Therapy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Yu J, Ostowari A, Gonda A, Mashayekhi K, Dayyani F, Hughes CCW, Senthil M. Exosomes as a Source of Biomarkers for Gastrointestinal Cancers. Cancers (Basel) 2023; 15:cancers15041263. [PMID: 36831603 PMCID: PMC9954462 DOI: 10.3390/cancers15041263] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 02/18/2023] Open
Abstract
Exosomes are small, lipid-bilayer bound extracellular vesicles of 40-160 nanometers in size that carry important information for intercellular communication. Exosomes are produced more by tumor cells than normal cells and carry tumor-specific content, such as DNA, RNA, and proteins, which have been implicated in tumorigenesis, tumor progression, and treatment response. Due to the critical role of exosomes in cancer development and progression, they can be exploited to develop specific biomarkers and therapeutic targets. Since exosomes are present in various biofluids, such as blood, saliva, urine, and peritoneal fluid, they are ideally suited to be developed as liquid biopsy tools for early diagnosis, molecular profiling, disease surveillance, and treatment response monitoring. In the past decade, numerous studies have been published about the functional significance of exosomes in a wide variety of cancers, with a particular focus on exosome-derived RNAs and proteins as biomarkers. In this review, utilizing human studies on exosomes, we highlight their potential as diagnostic, prognostic, and predictive biomarkers in gastrointestinal cancers.
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Affiliation(s)
- Jingjing Yu
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Arsha Ostowari
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Amber Gonda
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Kiarash Mashayekhi
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Farshid Dayyani
- Division of Hematology/Oncology, Department of Medicine, University of California, Irvine Medical Center, Orange, CA 92868, USA
| | - Christopher C. W. Hughes
- Department of Molecular Biology & Biochemistry and Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA
| | - Maheswari Senthil
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA
- Correspondence:
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Luo ZD, Wang YF, Zhao YX, Yu LC, Li T, Fan YJ, Zeng SJ, Zhang YL, Zhang Y, Zhang X. Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential. World J Gastroenterol 2023; 29:1-18. [PMID: 36683709 PMCID: PMC9850945 DOI: 10.3748/wjg.v29.i1.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/11/2022] [Accepted: 11/04/2022] [Indexed: 01/04/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.
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Affiliation(s)
- Zheng-Dong Luo
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yi-Feng Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yu-Xiao Zhao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Long-Chen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Tian Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Ying-Jing Fan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Shun-Jie Zeng
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yan-Li Zhang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
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Abstract
Peripheral blood is a source for liquid biopsy, which can meet the requirements of pretreatment disease typing to determine precise targeted therapy and monitoring of posttreatment minimal residual disease monitoring. Compared with ctDNA and CTC, exosomes have a higher concentration, good biostability, biocompatibility, low immunogenicity, and low toxicity in peripheral blood. Tumors generally secrete a large amounts of exosomes, which have potential pathophysiological roles in tumor progression. With the continuous improvement of liquid biopsy technology, many researchers have found that exosomes are the key for tumor PD-L1 to exert its role, which may be the mechanism that leads to PD-L1 and/or PD-1 inhibitor therapy resistance. Namely, tumor-derived exosomes may mediate systemic immunosuppression against PD-1 or PD-L1 inhibitor therapy, endogenous tumor cell-derived exosomal PD-L1, and tumor microenvironment-derived exosomes. Induction of PD-L1 by exosomes may be a crucial mechanisms of exosome-mediated antitumor immune tolerance. This article reviews the relationship between the detection of peripheral blood exosomal PD-L1 and tumor progression and the mechanism of exosomal PD-L1 in tumor immunotherapy.
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Affiliation(s)
- Rui Wang
- Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, China
- Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
| | - Yanjia Yang
- Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, China
- Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
| | - Jiajun Huang
- Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China
| | - Yandan Yao
- Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, China.
- Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, China.
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Xu P, Cheng S, Wang X, Jiang S, He X, Tang L, Wu N, Yang Z. The hsa_circ_0039857/miR-338-3p/RAB32 axis promotes the malignant progression of colorectal cancer. BMC Gastroenterol 2022; 22:530. [PMID: 36539702 PMCID: PMC9764720 DOI: 10.1186/s12876-022-02622-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a prevalent malignancy of the gastrointestinal. Circular RNAs (circRNAs) act as important roles in CRC malignant progression. However, the role of circ_0039857 in CRC is still unclear. Therefore, this study aimed to explore the function and mechanism of hsa_circ_0039857 in the CRC. METHODS The mRNA and protein expression were measured via RT-qPCR. RNase R assay and Actinomycin D were employed to evaluate the stability of circ_0039857. Functional experiments, such as proliferation and apoptosis, were applied to study the function of circ_0039857 in CRC cells. The underlying mechanisms of circ_0039857 were then analyzed by bioinformatics, dual-luciferase reporter gene assay, RNA pull-down and rescue experiments. RESULTS We revealed that circ_0039857 was significantly enhanced in CRC. Circ_0039857 was stabler than linear RNA in cells and valuable for the disease diagnosis. In addition, circ_0039857 knockdown inhibited proliferation and promoted apoptosis. Mechanistically, circ_0039857 positively regulated the expression of RAB32 via sponging miR-338-3p. CONCLUSION This study demonstrated that circ_0039857 knockdown suppressed CRC malignant progression through miR-338-3p/RAB32 axis. Most importantly, this will help us to better understand the circRNA network in CRC, and may find potential biomarkers and targets for CRC clinical treatment.
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Affiliation(s)
- Pei Xu
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Siying Cheng
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Xianwei Wang
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Shuming Jiang
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Xiaoyan He
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Lina Tang
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Ning Wu
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
| | - Zhirong Yang
- Department of Pathology, People’s Hospital of De Yang City, No. 173, Section 1 of North Taishan Road, Jingyang District, Deyang, 618000 Sichuan China
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Zhang W, Jiang Z, Tang D. The value of exosome-derived noncoding RNAs in colorectal cancer proliferation, metastasis, and clinical applications. Clin Transl Oncol 2022; 24:2305-2318. [PMID: 35921060 DOI: 10.1007/s12094-022-02908-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 07/23/2022] [Indexed: 11/26/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer in the world today, and its incidence and mortality rates are increasing every year. The ease of proliferation and metastasis of CRC has long been an important reason for its high mortality rate. Exosomes serve as key mediators that mediate communication between tumor cells and various other cells. Non-coding RNAs (ncRNAs) have been shown to play a key role in apoptosis, immunosuppression and proliferation metastasis in cancer. ncRNAs are loaded on exosomes and initiate the onset of metastasis by promoting epithelial-mesenchymal transition (EMT) at the primary site of the tumor. Meanwhile, exosome-derived ncRNAs construct a pre-metastatic niche (PMN) for CRC metastasis by forming an inflammatory microenvironment in distant organs, immunosuppression, and promoting angiogenesis and remodeling of the extracellular matrix. Here, we summarize the specific mechanisms associated with exosome-derived ncRNAs promoting local invasion and metastasis in CRC. Finally, we focus on their value for clinical application in future CRC diagnosis and treatment.
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Affiliation(s)
- Wenjie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Zhengting Jiang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu Province Hospital, Yangzhou University, Yangzhou, 225001, China.
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Long F, Tian L, Chai Z, Li J, Tang Y, Liu M. Identification of stage-associated exosome miRNAs in colorectal cancer by improved robust and corroborative approach embedded miRNA-target network. Front Med (Lausanne) 2022; 9:881788. [PMID: 36237545 PMCID: PMC9551196 DOI: 10.3389/fmed.2022.881788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 09/09/2022] [Indexed: 12/24/2022] Open
Abstract
Background Colorectal cancer (CRC) is a common gastrointestinal tumor with high morbidity and mortality. At the molecular level, patients at different stages present considerable heterogeneity. Although the miRNA in exosome is an effective biomarker to reveal tumor progression, studies based on stage-associated exosome miRNA regulatory network analysis still lacking. This study aims to identify CRC stage-associated exosome miRNAs and reveal their potential function in tumor progression. Methods In this study, serum and cellular exosome miRNA expression microarrays associated with CRC were downloaded from GEO database. Stage-common (SC) and stage-specific (SS) differentially expressed miRNAs were extracted and their targets were identified based on 11 databases. Furthermore, miRNA SC and SS regulatory function networks were built based on the CRC phenotypic relevance of miRNA targets, and the corresponding transcription factors were identified. Concurrently, the potential stage-associated miRNAs were identified by receiver-operating characteristic (ROC) curve analysis, survival analysis, drug response analysis, ceRNA analysis, pathway analysis and a comprehensive investigation of 159 publications. Results Ten candidate stage-associated miRNAs were identified, with three SC (miR-146a-5p, miR-22-3p, miR-23b-3p) and seven SS (I: miR-301a-3p, miR-548i; IIIA: miR-23a-3p; IV: miR-194-3p, miR-33a-3p, miR-485-3p, miR-194-5p) miRNAs. Additionally, their targets were enriched in several vital cancer-associated pathways such as TGF-beta, p53, and hippo signaling pathways. Moreover, five key hotspot target genes (CCNA2, MAPK1, PTPRD, MET, and CDKN1A) were demonstrated to associated with better overall survival in CRC patients. Finally, miR-23b-3p, miR-301a-3p and miR-194-3p were validated being the most stably expressed stage-associated miRNAs in CRC serum exosomes, cell exosomes and tissues. Conclusions These CRC stage-associated exosome miRNAs aid to further mechanism research of tumor progression and provide support for better clinical management in patients with different stages.
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An electrochemical biosensor for exosome detection based on covalent organic frameworks conjugated with DNA and horseradish peroxidase. J Electroanal Chem (Lausanne) 2022. [DOI: 10.1016/j.jelechem.2022.116576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Ashekyan O, Abdallah S, Shoukari AA, Chamandi G, Choubassy H, Itani ARS, Alwan N, Nasr R. Spotlight on Exosomal Non-Coding RNAs in Breast Cancer: An In Silico Analysis to Identify Potential lncRNA/circRNA-miRNA-Target Axis. Int J Mol Sci 2022; 23:8351. [PMID: 35955480 PMCID: PMC9369058 DOI: 10.3390/ijms23158351] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 12/12/2022] Open
Abstract
Breast cancer (BC) has recently become the most common cancer type worldwide, with metastatic disease being the main reason for disease mortality. This has brought about strategies for early detection, especially the utilization of minimally invasive biomarkers found in various bodily fluids. Exosomes have been proposed as novel extracellular vesicles, readily detectable in bodily fluids, secreted from BC-cells or BC-tumor microenvironment cells, and capable of conferring cellular signals over long distances via various cargo molecules. This cargo is composed of different biomolecules, among which are the novel non-coding genome products, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and the recently discovered circular RNA (circRNA), all of which were found to be implicated in BC pathology. In this review, the diverse roles of the ncRNA cargo of BC-derived exosomes will be discussed, shedding light on their primarily oncogenic and additionally tumor suppressor roles at different levels of BC tumor progression, and drug sensitivity/resistance, along with presenting their diagnostic, prognostic, and predictive biomarker potential. Finally, benefiting from the miRNA sponging mechanism of action of lncRNAs and circRNAs, we established an experimentally validated breast cancer exosomal non-coding RNAs-regulated target gene axis from already published exosomal ncRNAs in BC. The resulting genes, pathways, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis could be a starting point to better understand BC and may pave the way for the development of novel diagnostic and prognostic biomarkers and therapeutics.
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Affiliation(s)
- Ohanes Ashekyan
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon;
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; (S.A.); (G.C.); (H.C.)
| | - Samira Abdallah
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; (S.A.); (G.C.); (H.C.)
| | - Ayman Al Shoukari
- Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon;
| | - Ghada Chamandi
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; (S.A.); (G.C.); (H.C.)
- INSERM U976, HIPI, Pathophysiology of Breast Cancer Team, Université de Paris, 75010 Paris, France
| | - Hayat Choubassy
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; (S.A.); (G.C.); (H.C.)
- Faculty of Sciences, Lebanese University, Beirut 11-0236, Lebanon
| | - Abdul Rahman S. Itani
- Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany;
- Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany
- Division of Inflammatory Stress in Stem Cells, Deutsches Krebsforschungszentrum (DKFZ) and DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
| | - Nisreen Alwan
- College of Health Sciences, Abu Dhabi University, Abu Dhabi 59911, United Arab Emirates
| | - Rihab Nasr
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 11-0236, Lebanon; (S.A.); (G.C.); (H.C.)
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Exosome-Derived Circ_0094343 Promotes Chemosensitivity of Colorectal Cancer Cells by Regulating Glycolysis via the miR-766-5p/TRIM67 Axis. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:2878557. [PMID: 35854778 PMCID: PMC9286929 DOI: 10.1155/2022/2878557] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/14/2022] [Accepted: 06/18/2022] [Indexed: 02/08/2023]
Abstract
Objective Currently, the role of circ_0094343 (circPTEN) on the chemosensitivity of CRC remains to be clarified. This study aimed to investigate the role and mechanism of exosome-delivered circ_0094343 in the proliferation, glycolysis, and chemosensitivity of colorectal cancer (CRC) cells. Methods Real-time quantitative polymerase chain reaction (qRT-PCR) was utilized to detect the expression level of circ_0094343, miR-766-5p, and TRIM67 (Tripartite motif-containing 67) in CRC clinical tissue samples and cells, transmission electron microscopy (TEM) to observe the morphology of exosomes, and nanoparticle tracking analysis (NTA) system to measure the diameter of exosomes. Besides, PKH67 fluorescent labeling was applied for assessing the level of exosome uptake by cells, MTT and cell clone formation assays for detecting cell proliferation and clone formation, respectively, and related kits for checking the glucose consumption, lactate production, and extracellular acidification rate (ECAR) in cells. Dual-luciferase reporter (DLR) gene assay was used for verifying the targeting relationship between circ_0094343 and miR-766-5p, miR-766-5p and TRIM67, RNA immunoprecipitation (RIP) experiment for the interaction between circ_0094343 and miR-766-5p, and Western blot for the protein level of exosome surface antigens (HSP70, CD63) and TRIM67 in cells in exosomes and cell lysates. Results circ_0094343 was significantly downregulated in CRC tissues, chemotherapy-resistant CRC tissues, and metastatic CRC tissues. Moreover, exosomes-carried circ_0094343 played an inhibitory role in the proliferation, clone formation and glycolysis of HCT116 cells. Meanwhile, it could also improve the chemosensitivity of HCT116 cells to 5-fluorouracil (5-FU), oxaliplatin (L-OHP), and doxorubicin (Dox). Additionally, circ_0094343 acted as a sponge for miR-766-5p, and miR-766-5p targeted and regulated TRIM67. In CRC tissues, miR-766-5p expression was negatively correlated with TRIM67 expression, while circ_0094343 was positively associated with TRIM67. Further, mechanistic validation also demonstrated that circ_0094343 could inhibit HCT116 cell proliferation, clone formation, glycolysis, and chemotherapy resistance via the miR-766-5p/TRIM67 axis. Conclusion circ_0094343 inhibited the proliferation, clone formation and glycolysis of CRC cells and improved their chemosensitivity to various chemotherapeutic drugs via the miR-766-5p/TRIM67 axis. This finding may provide new insights into the treatment of CRC.
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Keremu A, Aila P, Tusun A, Abulikemu M, Zou X. Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway. Eur J Histochem 2022; 66. [PMID: 35730574 PMCID: PMC9251612 DOI: 10.4081/ejh.2022.3394] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/27/2022] [Indexed: 11/23/2022] Open
Abstract
Osteosarcoma (OS) is a kind of malignant tumor originating from mesenchymal tissues. Bone mesenchymal stem cells-derived extracellular vesicles (BMSCs-EVs) can play important roles in OS. This study investigated the mechanism of BMSCs-EVs on OS. BMSC surface antigens and adipogenic and osteogenic differentiation were detected by flow cytometry, and oil red O and alizarin red staining. EVs were isolated from BMSCs by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot (WB). miR-206 and neurensin-2 (NRSN2) levels in human osteoblast hFOB 1.19 or OS cells (143B, MG-63, Saos2, HOS) were detected by RT-qPCR. Human OS cells with lower miR-206 levels were selected and treated with BMSCs-EVs or pSUPER-NRSN2. The uptake of EVs by 143B cells, cell proliferation, apoptosis, invasion, and migration were detected by immunofluorescence, 5-ethynyl-2’-deoxyuridine (EdU) and colony formation assays, flow cytometry, scratch test, and transwell assays. The binding sites between miR-206 and NRSN2 were predicted by Starbase database and verified by dual-luciferase assay. The OS xenograft model was established and treated with BMSCs-EVs. Tumor growth rate and volume, cell proliferation, and p-ERK1/2, ERK1/2, and Bcl-xL levels were detected by vernier caliper, immunohistochemistry, and WB. BMSCs-EVs were successfully extracted. miR-206 was diminished and NRSN2 was promoted in OS cells. BMSCs-EVs inhibited proliferation, migration, and invasion, and promoted apoptosis of OS cells. BMSCs-EVs carried miR-206 into OS cells. Inhibition of miR-206 in EVs partially reversed the inhibitory effect of EVs on malignant behaviors of OS cells. miR-206 targeted NRSN2. Overexpression of NRSN2 reversed the inhibitory effect of EVs on OS cells. NRSN2 activated the ERK1/2-Bcl-xL pathway. BMSC-EVs inhibited OS growth in vivo. In summary, BMSC-EVs targeted NRSN2 and inhibited the ERK1/2-Bcl-xL pathway by carrying miR-206 into OS cells, thus inhibiting OS progression.
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Affiliation(s)
- Alimu Keremu
- Orthopedic Center, First People's Hospital of Kashgar, Xinjiang.
| | - Pazila Aila
- Orthopedic Center, First People's Hospital of Kashgar, Xinjiang.
| | - Aikebaier Tusun
- Orthopedic Center, First People's Hospital of Kashgar, Xinjiang.
| | | | - Xiaoguang Zou
- Orthopedic Center, First People's Hospital of Kashgar, Xinjiang.
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The role of long non-coding RNAs in angiogenesis and anti-angiogenic therapy resistance in cancer. MOLECULAR THERAPY. NUCLEIC ACIDS 2022; 28:397-407. [PMID: 35505957 PMCID: PMC9038520 DOI: 10.1016/j.omtn.2022.03.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
It is well known that long non-coding RNAs (lncRNAs) play an important role in the regulation of tumor genesis and development. They can modulate gene expression of transcriptional regulation, epigenetic regulation of chromatin modification, and post-transcriptional regulation, thus influencing the biological behavior of tumors, such as cell proliferation, apoptosis, cell cycle, invasion, and migration. Tumor angiogenesis not only provides nutrients and helps excrete metabolites, but it also opens a pathway for tumor metastasis. Anti-angiogenic therapy has become one of the effective treatment methods for tumor. But its drug resistance leads to the limitation of clinical application. Recent studies have shown that lncRNAs are closely related to tumor angiogenesis and anti-angiogenic therapy resistance, which provides a new direction for tumor research. lncRNAs are expected to be new targets for tumor therapy. For the first time to our knowledge, this paper reviews advancement of lncRNAs in tumor angiogenesis and anti-angiogenic therapy resistance and further discusses their potential clinical application.
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Pirisinu M, Pham TC, Zhang DX, Hong TN, Nguyen LT, Le MT. Extracellular vesicles as natural therapeutic agents and innate drug delivery systems for cancer treatment: Recent advances, current obstacles, and challenges for clinical translation. Semin Cancer Biol 2022; 80:340-355. [PMID: 32977006 DOI: 10.1016/j.semcancer.2020.08.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 08/11/2020] [Accepted: 08/12/2020] [Indexed: 12/13/2022]
Abstract
As cancer poses a significant threat to the well-being of humans on a global scale, many researchers have embarked on the search for effective anticancer therapeutic agents. In recent years, many drugs have been shown to have extraordinary anticancer effects. However, in a lot of cases the treatment is accompanied by undesirable side effects due to some intrinsic properties linked to the therapeutic agents, such as poor targeting selectivity and short half-life in the circulation. In this regard, extracellular vesicles (EVs), a diverse family of natural cell-derived vesicles, steal the show as potential anticancer immunotherapy or delivery vectors of anticancer agents since they are an innate mechanism of intercellular communication. Here, we describe some of the most hotly-debated issues regarding the use of EVs as anticancer therapeutics. First, we review the biology of EVs providing the most up-to-date definition of EVs as well as highlighting their circulation kinetics and homing properties. Next, we share our views on popular methods reported for EV isolation, characterization, and functional analysis. Pioneering and innovative reports along with emerging challenges in the field of EV imaging and EV drug loading strategies are then discussed. Finally, we examine in detail the therapeutic application of EVs in cancer treatment, including their role in cancer immunotherapy and as natural delivery systems for anticancer agents including natural compounds such as paclitaxel and doxorubicin. We consider standardised protocols and proper analytical approaches to be crucial in improving the reproducibility and rigor in EV research and ensuring the successful translation of EVs as anticancer therapeutics.
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Affiliation(s)
- Marco Pirisinu
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR of China, China
| | - Tin Chanh Pham
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR of China, China
| | - Daniel Xin Zhang
- Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR of China, China; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
| | - Tran Nguyen Hong
- Department of Pharmacology and Biochemistry, Vietnam Institute of Medicinal Materials, Hanoi, Vietnam
| | - Lap Thi Nguyen
- Department of Biochemistry, Hanoi University of Pharmacy, Hanoi, Vietnam
| | - Minh Tn Le
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR of China, China.
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44
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Bakhsh T, Alhazmi S, Alburae NA, Farsi A, Alzahrani F, Choudhry H, Bahieldin A. Exosomal miRNAs as a Promising Source of Biomarkers in Colorectal Cancer Progression. Int J Mol Sci 2022; 23:ijms23094855. [PMID: 35563246 PMCID: PMC9103063 DOI: 10.3390/ijms23094855] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/24/2022] [Accepted: 04/26/2022] [Indexed: 01/27/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common type of cancer worldwide amongst males and females. CRC treatment is multidisciplinary, often including surgery, chemotherapy, and radiotherapy. Early diagnosis of CRC can lead to treatment initiation at an earlier stage. Blood biomarkers are currently used to detect CRC, but because of their low sensitivity and specificity, they are considered inadequate diagnostic tools and are used mainly for following up patients for recurrence. It is necessary to detect novel, noninvasive, specific, and sensitive biomarkers for the screening and diagnosis of CRC at earlier stages. The tumor microenvironment (TME) has an essential role in tumorigenesis; for example, extracellular vesicles (EVs) such as exosomes can play a crucial role in communication between cancer cells and different components of TME, thereby inducing tumor progression. The importance of miRNAs that are sorted into exosomes has recently attracted scientists’ attention. Some unique sequences of miRNAs are favorably packaged into exosomes, and it has been illustrated that particular miRNAs can be directed into exosomes by special mechanisms that occur inside the cells. This review illustrates and discusses the sorted and transported exosomal miRNAs in the CRC microenvironment and their impact on CRC progression as well as their potential use as biomarkers.
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Affiliation(s)
- Tahani Bakhsh
- Department of Biology, Faculty of Science, Jeddah University, Jeddah 21589, Saudi Arabia
- Correspondence:
| | - Safiah Alhazmi
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.A.); (A.B.)
| | - Najla Ali Alburae
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.A.); (A.B.)
| | - Ali Farsi
- Department of Surgry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Faisal Alzahrani
- King Fahd Medical Research Center, Embryonic Stem Cells Unit, Department of Biochemistry, Faculty of Science, King AbdulAziz University, Jeddah 21589, Saudi Arabia;
- Centre of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Hani Choudhry
- Centre of Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
- Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ahmed Bahieldin
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia; (S.A.); (N.A.A.); (A.B.)
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Lin K, Baenke F, Lai X, Schneider M, Helm D, Polster H, Rao VS, Ganig N, Wong FC, Seifert L, Seifert AM, Jahnke B, Kretschmann N, Ziemssen T, Klupp F, Schmidt T, Schneider M, Han Y, Weber TF, Plodeck V, Nebelung H, Schmitt N, Korell F, Köhler BC, Riediger C, Weitz J, Rahbari NN, Kahlert C. Comprehensive proteomic profiling of serum extracellular vesicles in patients with colorectal liver metastases identifies a signature for non-invasive risk stratification and early-response evaluation. Mol Cancer 2022; 21:91. [PMID: 35365178 PMCID: PMC8973547 DOI: 10.1186/s12943-022-01562-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 03/14/2022] [Indexed: 11/10/2022] Open
Affiliation(s)
- Kuailu Lin
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Franziska Baenke
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, Heidelberg, Germany
| | - Xixi Lai
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,Department of Respiratory and Critical Care Medicine, College of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Martin Schneider
- MS-Based Protein Analysis Unit, German Cancer Research Centre (DKFZ), Heidelberg, Germany
| | - Dominic Helm
- MS-Based Protein Analysis Unit, German Cancer Research Centre (DKFZ), Heidelberg, Germany
| | - Heike Polster
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Venkatesh S Rao
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Nicole Ganig
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, Heidelberg, Germany
| | - Fang Cheng Wong
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Lena Seifert
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, Heidelberg, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden, Heidelberg, Germany
| | - Adrian M Seifert
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, Heidelberg, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden, Heidelberg, Germany
| | - Beatrix Jahnke
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Nicole Kretschmann
- MS Center, Centre of Clinical Neuroscience, Department of Neurology, Carl Gustav Carus University Hospital Dresden, Dresden, Germany
| | - Tjalf Ziemssen
- MS Center, Centre of Clinical Neuroscience, Department of Neurology, Carl Gustav Carus University Hospital Dresden, Dresden, Germany
| | - Fee Klupp
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Klinik Für Allgemein, Viszeral-, Tumor- Und Transplantationschirurgie, Universitätklinikum Köln, Kerpener Str. 62, 50937, Köln, Germany
| | - Martin Schneider
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Yi Han
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Tim F Weber
- Diagnostic and Interventional Radiology (DiR), Heidelberg University Hospital, Im Neuenheimer Feld 420, 69120, Heidelberg, Germany
| | - Verena Plodeck
- Department of Diagnostic and Interventional Radiology, Carl Gustav Carus University Hospital Dresden, Dresden, Germany
| | - Heiner Nebelung
- Department of Diagnostic and Interventional Radiology, Carl Gustav Carus University Hospital Dresden, Dresden, Germany
| | - Nathalie Schmitt
- Department of Medical Oncology, National Center for Tumour Diseases, Liver Cancer Centre Heidelberg, University Hospital Heidelberg, University Hospital Heidelberg, Heidelberg, Germany
| | - Felix Korell
- Department of Medical Oncology, National Center for Tumour Diseases, Liver Cancer Centre Heidelberg, University Hospital Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.,Department of Medicine V, University of Heidelberg, Heidelberg, Germany
| | - Bruno C Köhler
- Department of Medical Oncology, National Center for Tumour Diseases, Liver Cancer Centre Heidelberg, University Hospital Heidelberg, University Hospital Heidelberg, Heidelberg, Germany.,German Cancer Consortium (DKTK), 69120, Heidelberg, Germany
| | - Carina Riediger
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.,German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, Heidelberg, Germany.,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden, Heidelberg, Germany
| | - Nuh N Rahbari
- Department of Surgery, Medical Faculty Mannheim, University Medicine Mannheim, University of Heidelberg, 68167, Mannheim, Germany.
| | - Christoph Kahlert
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital Dresden, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany. .,German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Partner Site Dresden, Heidelberg, Germany. .,National Center for Tumor Diseases (NCT/UCC), Partner Site Dresden, Heidelberg, Germany.
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Xu T, He B, Sun H, Xiong M, Nie J, Wang S, Pan Y. Novel insights into the interaction between N6-methyladenosine modification and circular RNA. MOLECULAR THERAPY. NUCLEIC ACIDS 2022; 27:824-837. [PMID: 35141044 PMCID: PMC8807973 DOI: 10.1016/j.omtn.2022.01.007] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
As the most prevalent type of RNA modification in eukaryotes, N6-methyladenosine (m6A) can modulate RNA fates such as processing, splicing, maturation, export, stability, translation, and degradation. Circular RNAs (circRNAs), a novel type of non-coding RNA (ncRNAs) characterized by a covalently closed loop structure, play an essential role in various physiological and pathological processes. Extensive studies have revealed that m6A modification is widespread in circRNAs and influences their biogenesis and functions. Intriguingly, circRNAs can affect m6A modification by regulating m6A regulatory proteins. In this review, we summarize the characteristics and biological functions of m6A and circRNAs and focus on recent advances in the interaction of m6A modification and circRNAs. In addition, the potential clinical applications of m6A modification and circRNAs in diagnosis and therapeutic targets are discussed.
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Affiliation(s)
- Tao Xu
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Huiling Sun
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Mengqiu Xiong
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Junjie Nie
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Shukui Wang
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
| | - Yuqin Pan
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
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Preethi KA, Selvakumar SC, Ross K, Jayaraman S, Tusubira D, Sekar D. Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer. Mol Cancer 2022; 21:54. [PMID: 35172817 PMCID: PMC8848669 DOI: 10.1186/s12943-022-01525-9] [Citation(s) in RCA: 112] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/26/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.
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Affiliation(s)
- K. Auxzilia Preethi
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu 600077 India
| | - Sushmaa Chandralekha Selvakumar
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu 600077 India
| | - Kehinde Ross
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
| | - Selvaraj Jayaraman
- Department of Biochemistry, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, 600077 India
| | - Deusdedit Tusubira
- Biochemistry Department, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Durairaj Sekar
- Centre for Cellular and Molecular Research, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu 600077 India
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Zhang X, Li T, Niu Q, Qin CJ, Zhang M, Wu GM, Li HZ, Li Y, Wang C, Du WF, Wang CY, Zhao Q, Zhao XD, Wang XL, Zhu JB. Genome-wide analysis of cell-Free DNA methylation profiling with MeDIP-seq identified potential biomarkers for colorectal cancer. World J Surg Oncol 2022; 20:21. [PMID: 35065650 PMCID: PMC8783473 DOI: 10.1186/s12957-022-02487-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 12/30/2021] [Indexed: 11/15/2022] Open
Abstract
Background Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. Methods Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. Results Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. Conclusions MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02487-4.
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Affiliation(s)
- Xin Zhang
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, No. 1158 Gongyuan East Road, Qingpu District, Shanghai, 201700, China
| | - Tao Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200025, China
| | - Qiang Niu
- Department of General Surgery, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, 200433, China
| | - Chang-Jiang Qin
- Department of Gastrointestinal Surgery, Huaihe Hospital of Henan University, Kaifeng, 475000, Henan, China
| | - Ming Zhang
- General Surgery, The People's Hospital of Wuhai, Wuhai, 010600, Inner Mongolia, China
| | - Guang-Ming Wu
- General Surgery, The People's Hospital of Wuhai, Wuhai, 010600, Inner Mongolia, China
| | - Hua-Zhong Li
- General Surgery, The People's Hospital of Wuhai, Wuhai, 010600, Inner Mongolia, China
| | - Yan Li
- Digestive Internal, The People's Hospital of Wuhai, No. 29 Huanghe East Street, Haibowan District, Wuhai, 010600, Inner Mongolia, China
| | - Chen Wang
- Digestive Internal, The People's Hospital of Wuhai, No. 29 Huanghe East Street, Haibowan District, Wuhai, 010600, Inner Mongolia, China
| | - Wen-Fei Du
- Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Chen-Yang Wang
- Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Qiang Zhao
- Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Xiao-Dong Zhao
- Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Xiao-Liang Wang
- Department of General Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, No. 1158 Gongyuan East Road, Qingpu District, Shanghai, 201700, China. .,Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China.
| | - Jian-Bin Zhu
- Digestive Internal, The People's Hospital of Wuhai, No. 29 Huanghe East Street, Haibowan District, Wuhai, 010600, Inner Mongolia, China.
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Cheng Z, Jiang S, Tao R, Ge H, Qin J. Activating transcription factor 3-activated long noncoding RNA forkhead box P4-antisense RNA 1 aggravates colorectal cancer progression by regulating microRNA-423-5p/nucleus accumbens associated 1 axis. Bioengineered 2022; 13:2114-2129. [PMID: 35034547 PMCID: PMC8973600 DOI: 10.1080/21655979.2021.2023798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) have vital roles in the progression of colorectal cancer (CRC). Forkhead box P4-antisense RNA 1 (FOXP4-AS1) showed a potential unfavorable prognostic factor for CRC, while its underlying mechanism remains elusive. Thus, the goal of this research is to determine mechanism of FOXP4-AS1 in CRC occurrence and development. Herein, a Dual-luciferase reporter assay was performed to assess the regulation of miR-423-5p to nucleus accumbens-associated protein 1 (NACC1) and activating transcription factor 3 (ATF3) to FOXP4-AS1 promoter. Hematoxylin-eosin (H&E) staining was performed to detect the pathological changes of tumor tissues. Flow cytometry, cell counting kit 8, Transwell, and wound healing assays were conducted to assess apoptosis, proliferation, migration, and invasion of CRC cells, respectively. The results showed that FOXP4-AS1 was highly expressed in CRC cell lines and tissues. CRC progression was promoted by the overexpression of FOXP4-AS1 in HTC116 cells and animal models. Furthermore, FOXP4-AS1 served as a molecular sponge for miR-423-5p, and NACC1 is a direct target of miR-423-5p. MiR-423-5p silencing or overexpression of NACC1 increased proliferation, migration, and invasion of HCT116 cells while suppressing apoptosis. We also found that the upregulation of FOXP4-AS1 was activated by ATF3 in CRC cells. Collectively, our results demonstrated that ATF3-activated FOXP4-AS1 aggravates CRC progression by regulating miR-423-5p/NACC1 axis, indicating a new target for CRC treatment.
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Affiliation(s)
- Zhouyang Cheng
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, JS, China
| | - Song Jiang
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, JS, China
| | - Ran Tao
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, JS, China
| | - Haipeng Ge
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, JS, China
| | - Jun Qin
- Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, JS, China
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50
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Ren L, Zeng F, Deng J, Bai Y, Chen K, Chen L, Sun L. Inflammatory osteoclasts-derived exosomes promote bone formation by selectively transferring lncRNA LIOCE into osteoblasts to interact with and stabilize Osterix. FASEB J 2022; 36:e22115. [PMID: 35032415 DOI: 10.1096/fj.202101106rr] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 11/26/2021] [Accepted: 12/08/2021] [Indexed: 01/08/2023]
Abstract
Bone loss is a hallmark of inflammatory bone diseases caused by aberrantly activated osteoclasts (OCLs). Studies have shown that OCLs exhibit various phenotypes and functions due to variations in the source(s) of precursor cells, cytokine expressions, and microenvironment-dependent factors. During these conditions, inflammatory osteoclasts (iOCLs) lose their immune-suppressive effect relative to OCLs under physiological conditions. This induces TNF α-producing CD4+ T cells in an antigen-dependent manner and finally leads to cascade amplification of iOCLs. OCL-derived exosomes have been reported to regulate OCL formation and inhibit the osteoblast activity. However, the specific function and mechanism of iOCL-derived exosomes on osteoblast have not been studied yet. In the present study, we compare the osteoblast promoting activities of iOCL-derived exosomes and OCL-derived exosomes. We found that iOCLs exosomes specifically target osteoblasts through ephrinA2/EphA2. Mechanistically, the lncRNA LIOCE is enriched in iOCL exosomes and promotes the osteoblast activity after being incorporated into osteoblasts. Furthermore, our results revealed that exosomal lncRNA LIOCE stabilizes osteogenic transcription factor Osterix by interacting and reducing the ubiquitination level of Osterix. This study demonstrated that the bone loss is alleviated in the inflammatory osteolysis mice model after injection of iOCL exosomes encapsulating lncRNA LIOCE. The role of exosomes encapsulating lncRNA LIOCE in promoting bone formation was well established in the rat bone repair model. Our results indicate that iOCL-derived exosomal lncRNA LIOCE promotes bone formation by upregulating Osx expression, and thus, the exosomes encapsulating lncRNA LIOCE may be an effective strategy to increase bone formation in osteoporosis and other bone metabolic disorders.
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Affiliation(s)
- Lingyan Ren
- Medical College, Guizhou University, Guiyang, China.,Department of Orthopedics, Guizhou Provincial People's Hospital, Guiyang, China.,Antenatal Diagnosis Centre, Guizhou Provincial People's Hospital, Guiyang, China
| | - Fanchun Zeng
- Bioengineering College, Chongqing University, Chongqing, China
| | - Jiezhong Deng
- Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yun Bai
- Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Kun Chen
- Center Lab, Guizhou Provincial People's Hospital, Guiyang, China
| | - Long Chen
- Department of Orthopedics, Guizhou Provincial People's Hospital, Guiyang, China
| | - Li Sun
- Medical College, Guizhou University, Guiyang, China.,Department of Orthopedics, Guizhou Provincial People's Hospital, Guiyang, China
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