|
1
|
Zhang B, Ma X, Zhou Y, Zhu B, Yu J, Liu H, Ma Y, Luan Y, Chen M. Diagnostic Value of Circulating microRNAs for Hepatocellular Carcinoma: Results of a Meta-analysis and Validation. Biochem Genet 2025:10.1007/s10528-024-11001-2. [PMID: 39751721 DOI: 10.1007/s10528-024-11001-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/09/2024] [Indexed: 01/04/2025]
Abstract
Mounting evidence suggests that circulating microRNAs (miRNAs) hold diagnostic value in various malignancies. To identify circulating miRNAs for the early diagnosis of hepatocellular carcinoma (HCC), we conducted a meta-analysis to evaluate the diagnostic utility of miRNAs in HCC and further validated the results of the meta-analysis. English articles published prior to December 2023 were retrieved from databases including PubMed, Embase, and Web of Science. A random-effects or fixed-effects model was applied depending on the heterogeneity among studies. The pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve (AUC) were calculated to assess diagnostic accuracy. Additionally, RT-qPCR and receiver operating characteristic (ROC) analyses were employed to further validate the findings. A total of 36 studies were included, involving 3362 patients with HCC and 2150 patients with chronic hepatitis. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.79 (95% CI 0.75-0.82), 0.79 (95% CI 0.73-0.84), and 14 (95% CI 9-22), respectively; the positive and negative likelihood ratios were 4.0 and 0.27, respectively; the area under the curve (AUC) in the summary receiver operating characteristic (ROC) was 0.85 (95% CI 0.82-0.88). Validation indicated a significant upregulation of miR-1246, miR-21, and miR-221 in HCC patients compared to those with chronic hepatitis (P < 0.01), while miR-122 and miR-26a were significantly downregulated (P < 0.01). Moreover, the validation results also demonstrated that serum levels of miR-21, miR-26a, miR-122, miR-221, and miR-1246 exhibit high sensitivity and specificity in the diagnosis of HCC. Circulating miRNAs may be promising biomarkers for HCC diagnosis.
Collapse
Affiliation(s)
- Bingqiang Zhang
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Xiaoyan Ma
- Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266111, Shandong, People's Republic of China
| | - Yang Zhou
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Boyang Zhu
- School of Clinical and Basic Medical Sciences, Shandong First Medical, University& Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, People's Republic of China
| | - Junmei Yu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - He Liu
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China
| | - Yongchao Ma
- College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266111, Shandong, People's Republic of China
| | - Yansong Luan
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China.
| | - Mengmeng Chen
- Qingdao Ruiside Medical Laboratory Co., LTD, Qingdao, 266111, Shandong, People's Republic of China.
| |
Collapse
|
|
2
|
Solhi R, Pourhamzeh M, Zarrabi A, Hassan M, Mirzaei H, Vosough M. Novel biomarkers for monitoring and management of hepatocellular carcinoma. Cancer Cell Int 2024; 24:428. [PMID: 39719624 DOI: 10.1186/s12935-024-03600-1] [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: 01/28/2024] [Accepted: 12/05/2024] [Indexed: 12/26/2024] Open
Abstract
Due to current challenges in the early detection, less than 40% of individuals diagnosed with hepatocellular carcinoma (HCC) are viable candidates for surgical intervention. Therefore, validating and launching of a novel precise diagnostic approach is essential for early diagnosis. Based on developing evidence using circulating tumor cells and their derivatives, circulating miRNAs, and extracellular vesicles (EVs), liquid biopsy may offer a reliable platform for the HCC's early diagnosis. Each liquid biopsy analyte may provide significant areas for diagnosis, prognostic assessment, and treatment monitoring of HCC patients depending on its kind, sensitivity, and specificity. The current review addresses potential clinical applications, current research, and future developments for liquid biopsy in HCC management.
Collapse
Affiliation(s)
- Roya Solhi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Mahsa Pourhamzeh
- Departments of Pathology and Medicine, UC San Diego, La Jolla, CA, USA
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey
| | - Moustapha Hassan
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
- Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
| |
Collapse
|
|
3
|
Yadav S, Maity P, Kapat K. The Opportunities and Challenges of Mesenchymal Stem Cells-Derived Exosomes in Theranostics and Regenerative Medicine. Cells 2024; 13:1956. [PMID: 39682706 DOI: 10.3390/cells13231956] [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: 10/25/2024] [Revised: 11/19/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Cell-secreted nanovesicles of endosomal origin, called exosomes, are vital for mediating intracellular communication. As local or distal transporters of intracellular cargo, they reflect the unique characteristics of secretory cells and establish cell-specific interactions via characteristic surface proteins and receptors. With the advent of rapid isolation, purification, and identification techniques, exosomes have become an attractive choice for disease diagnosis (exosomal content as biomarkers), cell-free therapy, and tissue regeneration. Mesenchymal stem cell (MSC)-derived exosomes (MSC-exosomes) display angiogenic, immune-modulatory, and other therapeutic effects crucial for cytoprotection, ischemic wound repair, myocardial regeneration, etc. The primary focus of this review is to highlight the widespread application of MSC-exosomes in therapeutics, theranostics, and tissue regeneration. After a brief introduction of exosome properties, biogenesis, isolation, and functions, recent studies on therapeutic and regenerative applications of MSC-exosomes are described, focusing on bone, cartilage, periodontal, cardiovascular, skin, and nerve regeneration. Finally, the review highlights the theranostic potential of exosomes followed by challenges, summary, and outlook.
Collapse
Affiliation(s)
- Sachin Yadav
- Department of Medical Devices, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kankurgachi, Kolkata 700054, West Bengal, India
| | - Pritiprasanna Maity
- School of Medicine, University of California Riverside, Riverside, CA 92525, USA
| | - Kausik Kapat
- Department of Medical Devices, National Institute of Pharmaceutical Education and Research Kolkata, 168, Maniktala Main Road, Kankurgachi, Kolkata 700054, West Bengal, India
| |
Collapse
|
|
4
|
Kouroumalis E, Tsomidis I, Voumvouraki A. Extracellular Vesicles in Viral Liver Diseases. Viruses 2024; 16:1785. [PMID: 39599900 PMCID: PMC11598962 DOI: 10.3390/v16111785] [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: 09/30/2024] [Revised: 11/12/2024] [Accepted: 11/15/2024] [Indexed: 11/29/2024] Open
Abstract
Extracellular vesicles (EVs) are bilayer vesicles released by cells in the microenvironment of the liver including parenchymal and non-parenchymal cells. They are the third important mechanism in the communications between cells, besides the secretion of cytokines and chemokines and the direct cell-to-cell contact. The aim of this review is to discuss the important role of EVs in viral liver disease, as there is increasing evidence that the transportation of viral proteins, all types of RNA, and viral particles including complete virions is implicated in the pathogenesis of both viral cirrhosis and viral-related hepatocellular carcinoma. The biogenesis of EVs is discussed and their role in the pathogenesis of viral liver diseases is presented. Their use as diagnostic and prognostic biomarkers is also analyzed. Most importantly, the significance of possible novel treatment strategies for liver fibrosis and hepatocellular carcinoma is presented, although available data are based on experimental evidence and clinical trials have not been reported.
Collapse
Affiliation(s)
- Elias Kouroumalis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Greece;
| | - Ioannis Tsomidis
- Laboratory of Gastroenterology and Hepatology, University of Crete Medical School, 71500 Heraklion, Greece;
| | - Argyro Voumvouraki
- 1st Department of Internal Medicine, AHEPA University Hospital, 54621 Thessaloniki, Greece;
| |
Collapse
|
|
5
|
Batista IA, Machado JC, Melo SA. Advances in exosomes utilization for clinical applications in cancer. Trends Cancer 2024; 10:947-968. [PMID: 39168775 DOI: 10.1016/j.trecan.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 07/04/2024] [Accepted: 07/25/2024] [Indexed: 08/23/2024]
Abstract
Exosomes are regarded as having transformative potential for clinical applications. Exosome-based liquid biopsies offer a noninvasive method for early cancer detection and real-time disease monitoring. Clinical trials are underway to validate the efficacy of exosomal biomarkers for enhancing diagnostic accuracy and predicting treatment responses. Additionally, engineered exosomes are being developed as targeted drug delivery systems that can navigate the bloodstream to deliver therapeutic agents to tumor sites, thus enhancing treatment efficacy while minimizing systemic toxicity. Exosomes also exhibit immunomodulatory properties, which are being harnessed to boost antitumor immune responses. In this review, we detail the latest advances in clinical trials and research studies, underscoring the potential of exosomes to revolutionize cancer care.
Collapse
Affiliation(s)
- Inês A Batista
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal
| | - José C Machado
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Departamento de Patologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; P.CCC Porto Comprehensive Cancer Centre, Raquel Seruca, Portugal
| | - Sonia A Melo
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Departamento de Patologia, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; P.CCC Porto Comprehensive Cancer Centre, Raquel Seruca, Portugal.
| |
Collapse
|
|
6
|
Takeda Y, Yamada D, Kobayashi S, Sasaki K, Iwagami Y, Tomimaru Y, Noda T, Takahashi H, Asaoka T, Shimizu J, Doki Y, Eguchi H. MicroRNA-26a-5p is a reliable biomarker in the adjuvant setting for pancreatic ductal adenocarcinoma. PLoS One 2024; 19:e0310328. [PMID: 39288140 PMCID: PMC11407630 DOI: 10.1371/journal.pone.0310328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/28/2024] [Indexed: 09/19/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after radical resection because of subclinical tumors. To manage them, a reliable biomarker that can indicate the presence of subclinical tumors and predict their chemosensitivity is required. This study aimed to identify a miRNA as a biomarker that can be used to individualize postoperative adjuvant chemotherapy using postoperative peripheral blood samples. Integrating miRNA microarray data from the blood of 18 patients with PDAC and the in vitro results regarding the phenotypes of chemoresistant PDAC cells, a candidate miRNA was identified. The relationships between candidate miRNA expression and chemosensitivity were examined in vitro and in clinical samples from other cohorts of 33 patients with recurrence. Comprehensive analyses of blood samples detected 5 candidate miRNAs. Of these, miR-26a-5p was considered a candidate biomarker of chemosensitive phenotypes. In validation experiments, chemosensitivity was inversely correlated with miR-26a-5p expression in vitro. Moreover, the ability of miR-26a-5p to predict chemosensitivity was clinically evaluated using blood samples. Patients with high miR-26a-5p expression in the blood after radical resection exhibited a significantly longer survival time after recurrence. Thus, we concluded that miR-26a-5p is a potentially useful biomarker for managing patients with PDAC, especially those undergoing adjuvant chemotherapy.
Collapse
Affiliation(s)
- Yu Takeda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Daisaku Yamada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Kazuki Sasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Surgery, Osaka Police Hospital, Osaka, Japan
| | - Junzo Shimizu
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| |
Collapse
|
|
7
|
Shetti D, Mallela VR, Ye W, Sharif M, Ambrozkiewicz F, Trailin A, Liška V, Hemminki K. Emerging role of circulating cell-free RNA as a non-invasive biomarker for hepatocellular carcinoma. Crit Rev Oncol Hematol 2024; 200:104391. [PMID: 38795877 DOI: 10.1016/j.critrevonc.2024.104391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 04/30/2024] [Accepted: 05/19/2024] [Indexed: 05/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a severe neoplastic disease associated with high morbidity and mortality rates. HCC is often detected at advanced stages leading to ineffective curative treatments. Recently, liquid biopsy has emerged as a non-invasive method to identify highly specific HCC biomarkers in bodily fluids such as blood, serum, urine, and saliva. Circulating cell-free nucleic acids (cfNAs), particularly cell-free DNA (cfDNA) and cell-free RNA (cfRNA), have become promising candidates for biomarkers in liquid biopsy applications. While cfDNA presented significant challenges, researchers have turned their attention to cfRNA, which can be efficiently identified through various methods and is considered a potential biomarker for cancer diagnosis and prognosis. This review primarily focuses on studies related to detecting various cfRNA in body fluids as biomarkers. The aim is to provide a summary of available information to assist researchers in their investigations and the development of new diagnostic and prognostic tools.
Collapse
Affiliation(s)
- Dattatrya Shetti
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic.
| | - Venkata Ramana Mallela
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Wenjing Ye
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Mahyar Sharif
- Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University,Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Filip Ambrozkiewicz
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Andriy Trailin
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic
| | - Václav Liška
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic; Department of Surgery, University Hospital in Pilsen and Faculty of Medicine in Pilsen, Charles University, Alej Svobody 80, Pilsen 323 00, Czech Republic
| | - Kari Hemminki
- Laboratory of Translational Cancer Genomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1665/76, Pilsen 323 00, Czech Republic; Department of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany
| |
Collapse
|
|
8
|
Fekry B, Ugartemendia L, Esnaola NF, Goetzl L. Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:2552. [PMID: 39061191 PMCID: PMC11274441 DOI: 10.3390/cancers16142552] [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: 06/20/2024] [Revised: 07/12/2024] [Accepted: 07/14/2024] [Indexed: 07/28/2024] Open
Abstract
This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles of ECVs. A unique aspect of this review is the emphasis on the circadian-controlled release and composition of exosomes, highlighting their potential as biomarkers for early cancer detection and monitoring metastasis. We also discuss how circadian rhythms affect multiple cancer-related pathways, proposing that disruptions in the circadian clock can alter tumor development and treatment response. Additionally, this review delves into the influence of circadian clock components on ECV biogenesis and their impact on reshaping the tumor microenvironment, a key component driving HCC progression. Finally, we address the potential clinical applications of ECVs, particularly their use as diagnostic tools and drug delivery vehicles, while considering the challenges associated with clinical implementation.
Collapse
Affiliation(s)
- Baharan Fekry
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.U.); (L.G.)
| | - Lierni Ugartemendia
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.U.); (L.G.)
| | - Nestor F. Esnaola
- Division of Surgical Oncology and Gastrointestinal Surgery, Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA;
| | - Laura Goetzl
- McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; (L.U.); (L.G.)
| |
Collapse
|
|
9
|
Luo X, Jiao L, Guo Q, Chen Y, Wang N, Wen Y, Song J, Chen H, Zhou J, Song X. Diagnostic model for hepatocellular carcinoma using small extracellular vesicle-propagated miRNA signatures. Front Mol Biosci 2024; 11:1419093. [PMID: 39006969 PMCID: PMC11239443 DOI: 10.3389/fmolb.2024.1419093] [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: 04/22/2024] [Accepted: 05/23/2024] [Indexed: 07/16/2024] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Small extracellular vesicles (sEVs) are bilayer lipid membrane vesicles containing RNA that exhibit promising diagnostic and prognostic potential as cancer biomarkers. Aims To establish a miRNA panel from peripheral blood for use as a noninvasive biomarker for the diagnosis of HCC. Methods sEVs obtained from plasma were profiled using high-throughput sequencing. The identified differential miRNA expression patterns were subsequently validated using quantitative real-time polymerase chain reaction analysis. Results The random forest method identified ten distinct miRNAs distinguishing HCC plasma from non-HCC plasma. During validation, miR-140-3p (p = 0.0001) and miR-3200-3p (p = 0.0017) exhibited significant downregulation. Enrichment analysis uncovered a notable correlation between the target genes of these miRNAs and cancer development. Utilizing logistic regression, we developed a diagnostic model incorporating these validated miRNAs. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.951, with a sensitivity of 90.1% and specificity of 87.8%. Conclusion These aberrantly expressed miRNAs delivered by sEVs potentially contribute to HCC pathology and may serve as diagnostic biomarkers for HCC.
Collapse
Affiliation(s)
- Xinyi Luo
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lin Jiao
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qin Guo
- Department of Laboratory Medicine, the First People's Hospital of Ziyang, Ziyang, China
| | - Yi Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Nian Wang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yang Wen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - JiaJia Song
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Hao Chen
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Juan Zhou
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xingbo Song
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
10
|
Tian Z, Zhang C, Wu M, Luo J, Zhou H, Duan Y, Li Y. Flexible-Arranged Biomimetic Array Integrated with Parallel Entropy-Driven Circuits for Ultrasensitive, Multiple, and Reliable Detection of Cancer-Related MicroRNAs. ACS Sens 2024; 9:1290-1300. [PMID: 38478991 DOI: 10.1021/acssensors.3c02183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/23/2024]
Abstract
With the emergence of microRNA (miRNA) as a promising biomarker in cancer diagnosis, it is significant to develop multiple analyses of miRNAs. However, it still faces difficulties in ensuring the sensitivity and accuracy during multiplex detection owing to the low abundance and experimental deviation of miRNAs. In this work, a flexible-arranged biomimetic array integrated with parallel entropy-driven circuits (EDCs) was developed for ultrasensitive, multiplex, reliable, and high-throughput detection of miRNAs. The biomimetic array was fabricated by arrangement of various photonic crystals (PCs) for adjustable photonic band gaps (PBGs) and specific fluorescence enhancement. Meanwhile, two cancer-related miRNAs and one reference miRNA were introduced as multiple analytes as a proof-of-concept. The parallel EDCs with negligible crosstalk were designed based on the modular property. Because of the one-to-one match between the emitted fluorescence of parallel EDCs and the PBGs of the flexible-arranged biomimetic array, the generated fluorescence signal triggered by target miRNAs can be enhanced on the corresponding domain of the array. Furthermore, the amplified signal of the array was detected with high-throughput scanning, which could reveal specific information on cancer-related miRNAs as well as reference miRNA, enhancing the abundance and reliability of the analysis. The proposed array has the merits of a modular design, flexible deployment, simple operation (nonenzymatic and isothermal), improved accuracy, high sensitivity, and multiplex analysis, showing potential in disease diagnosis.
Collapse
Affiliation(s)
- Ziyi Tian
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China
| | - Chuyan Zhang
- Precision Medicine Center, Medical Equipment Innovation Research Center, Med-X Center for Manufacturing, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China
| | - Mengfan Wu
- Research Center of Analytical Instrumentation, School of Mechanical Engineering, Sichuan University, Chengdu, Sichuan 610065, P. R. China
| | - Jie Luo
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China
| | - Huiling Zhou
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China
| | - Yixiang Duan
- Research Center of Analytical Instrumentation, School of Mechanical Engineering, Sichuan University, Chengdu, Sichuan 610065, P. R. China
| | - Yongxin Li
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China
| |
Collapse
|
|
11
|
Yoo JS, Kang MK. Clinical significance of exosomal noncoding RNAs in hepatocellular carcinoma: a narrative review. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2024; 42:4. [PMID: 38325815 PMCID: PMC11812098 DOI: 10.12701/jyms.2023.01186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/20/2023] [Accepted: 12/30/2023] [Indexed: 02/09/2024]
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, with poor prognosis owing to its high frequency of recurrence and metastasis. Moreover, most patients are diagnosed at an advanced stage owing to a lack of early detection markers. Exosomes, which are characterized by their cargos of stable intracellular messengers, such as DNA, RNA, proteins, and lipids, play a crucial role in regulating cell differentiation and HCC development. Recently, exosomal noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, have become increasingly important diagnostic, prognostic, and predictive markers of HCC. Herein, we discuss the clinical implications of exosomal ncRNAs, specifically those within the HCC regulatory network.
Collapse
Affiliation(s)
- Jae Sung Yoo
- Department of Gastroenterology and Hepatology, The Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, Korea
| | - Min Kyu Kang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| |
Collapse
|
|
12
|
Li Y, Sui S, Goel A. Extracellular vesicles associated microRNAs: Their biology and clinical significance as biomarkers in gastrointestinal cancers. Semin Cancer Biol 2024; 99:5-23. [PMID: 38341121 PMCID: PMC11774199 DOI: 10.1016/j.semcancer.2024.02.001] [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: 10/13/2023] [Revised: 01/26/2024] [Accepted: 02/04/2024] [Indexed: 02/12/2024]
Abstract
Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver, are associated with high mortality and morbidity rates worldwide. One of the underlying reasons for the poor survival outcomes in patients with these malignancies is late disease detection, typically when the tumor has already advanced and potentially spread to distant organs. Increasing evidence indicates that earlier detection of these cancers is associated with improved survival outcomes and, in some cases, allows curative treatments. Consequently, there is a growing interest in the development of molecular biomarkers that offer promise for screening, diagnosis, treatment selection, response assessment, and predicting the prognosis of these cancers. Extracellular vesicles (EVs) are membranous vesicles released from cells containing a repertoire of biological molecules, including nucleic acids, proteins, lipids, and carbohydrates. MicroRNAs (miRNAs) are the most extensively studied non-coding RNAs, and the deregulation of miRNA levels is a feature of cancer cells. EVs miRNAs can serve as messengers for facilitating interactions between tumor cells and the cellular milieu, including immune cells, endothelial cells, and other tumor cells. Furthermore, recent years have witnessed considerable technological advances that have permitted in-depth sequence profiling of these small non-coding RNAs within EVs for their development as promising cancer biomarkers -particularly non-invasive, liquid biopsy markers in various cancers, including GI cancers. Herein, we summarize and discuss the roles of EV-associated miRNAs as they play a seminal role in GI cancer progression, as well as their promising translational and clinical potential as cancer biomarkers as we usher into the area of precision oncology.
Collapse
Affiliation(s)
- Yuan Li
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA, USA; Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Silei Sui
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA, USA; Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA, USA.
| |
Collapse
|
|
13
|
Guo J, Kong S, Lian Y, Zhao M. Recent bio-applications of covalent organic framework-based nanomaterials. Chem Commun (Camb) 2024; 60:918-934. [PMID: 38168699 DOI: 10.1039/d3cc04368a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Appearing as a new class of functional organic materials, covalent organic frameworks (COFs) have aroused a huge wave of interest in versatile fields ever since they were first proposed in 2005. Thanks to but not limited to their ultralight weights, high surface areas, ordered channels, variable functional groups and well-defined crystal structures, the applications of COF-based biomaterials in the fields of drug loading and delivery, photodynamic therapy, photothermal therapy, bioimaging, etc. are comprehensively summarized and introduced. The existing challenges and future prospects for this emerging but hot research direction are also discussed. It is hoped that this review will serve as a guidance for future research on COFs as multifunctional bioplatforms.
Collapse
Affiliation(s)
- Jun Guo
- State Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, China.
| | - Shuyue Kong
- State Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, China.
- Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Institute of Molecular Aggregation Science, Tianjin University, Tianjin 300072, China.
| | - Ye Lian
- State Key Laboratory of Separation Membranes and Membrane Processes, School of Chemistry, Tiangong University, Tianjin 300387, China.
| | - Meiting Zhao
- Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Institute of Molecular Aggregation Science, Tianjin University, Tianjin 300072, China.
| |
Collapse
|
|
14
|
Moeinafshar A, Nouri M, Shokrollahi N, Masrour M, Behnam A, Tehrani Fateh S, Sadeghi H, Miryounesi M, Ghasemi MR. Non-coding RNAs as potential therapeutic targets for receptor tyrosine kinase signaling in solid tumors: current status and future directions. Cancer Cell Int 2024; 24:26. [PMID: 38200584 PMCID: PMC10782702 DOI: 10.1186/s12935-023-03203-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 12/27/2023] [Indexed: 01/12/2024] Open
Abstract
This review article presents an in-depth analysis of the current state of research on receptor tyrosine kinase regulatory non-coding RNAs (RTK-RNAs) in solid tumors. RTK-RNAs belong to a class of non-coding RNAs (nc-RNAs) responsible for regulating the expression and activity of receptor tyrosine kinases (RTKs), which play a critical role in cancer development and progression. The article explores the molecular mechanisms through which RTK-RNAs modulate RTK signaling pathways and highlights recent advancements in the field. This include the identification of potential new RTK-RNAs and development of therapeutic strategies targeting RTK-RNAs. While the review discusses promising results from a variety of studies, encompassing in vitro, in vivo, and clinical investigations, it is important to acknowledge the challenges and limitations associated with targeting RTK-RNAs for therapeutic applications. Further studies involving various cancer cell lines, animal models, and ultimately, patients are necessary to validate the efficacy of targeting RTK-RNAs. The specificity of ncRNAs in targeting cellular pathways grants them tremendous potential, but careful consideration is required to minimize off-target effects, the article additionally discusses the potential clinical applications of RTK-RNAs as biomarkers for cancer diagnosis, prognosis, and treatment. In essence, by providing a comprehensive overview of the current understanding of RTK-RNAs in solid tumors, this review emphasizes their potential as therapeutic targets for cancer while acknowledging the associated challenges and limitations.
Collapse
Affiliation(s)
- Aysan Moeinafshar
- Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Nouri
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nima Shokrollahi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Masrour
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Center for Orthopedic Trans-Disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirmohammad Behnam
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahand Tehrani Fateh
- Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Sadeghi
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Miryounesi
- Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad-Reza Ghasemi
- Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
15
|
Tsoneva DK, Ivanov MN, Vinciguerra M. Liquid Liver Biopsy for Disease Diagnosis and Prognosis. J Clin Transl Hepatol 2023; 11:1520-1541. [PMID: 38161500 PMCID: PMC10752811 DOI: 10.14218/jcth.2023.00040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 05/24/2023] [Accepted: 06/07/2023] [Indexed: 01/03/2024] Open
Abstract
Liver diseases are a major burden worldwide, the scope of which is expected to further grow in the upcoming years. Clinically relevant liver dysfunction-related blood markers such as alanine aminotransferase and aspartate aminotransferase have limited accuracy. Nowadays, liver biopsy remains the gold standard for several liver-related pathologies, posing a risk of complication due to its invasive nature. Liquid biopsy is a minimally invasive approach, which has shown substantial potential in the diagnosis, prognosis, and monitoring of liver diseases by detecting disease-associated particles such as proteins and RNA molecules in biological fluids. Histones are the core components of the nucleosomes, regulating essential cellular processes, including gene expression and DNA repair. Following cell death or activation of immune cells, histones are released in the extracellular space and can be detected in circulation. Histones are stable in circulation, have a long half-life, and retain their post-translational modifications. Here, we provide an overview of the current research on histone-mediated liquid biopsy methods for liver diseases, with a focus on the most common detection methods.
Collapse
Affiliation(s)
- Desislava K. Tsoneva
- Department of Medical Genetics, Medical University of Varna, Varna, Bulgaria
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
| | - Martin N. Ivanov
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
- Department of Anatomy and Cell Biology, Research Institute, Medical University of Varna, Varna, Bulgaria
| | - Manlio Vinciguerra
- Department of Stem Cell Biology and Transplantology, Research Institute, Medical University of Varna, Varna, Bulgaria
- Faculty of Health, Liverpool John Moores University, Liverpool, United Kingdom
| |
Collapse
|
|
16
|
Manea I, Iacob R, Iacob S, Cerban R, Dima S, Oniscu G, Popescu I, Gheorghe L. Liquid biopsy for early detection of hepatocellular carcinoma. Front Med (Lausanne) 2023; 10:1218705. [PMID: 37809326 PMCID: PMC10556479 DOI: 10.3389/fmed.2023.1218705] [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: 05/08/2023] [Accepted: 08/30/2023] [Indexed: 10/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients' stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.
Collapse
Affiliation(s)
- Ioana Manea
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Speranta Iacob
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Razvan Cerban
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Simona Dima
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Gabriel Oniscu
- Transplant Division, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden
| | - Irinel Popescu
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Liliana Gheorghe
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, Romania
| |
Collapse
|
|
17
|
Ugonabo O, Udoh UAS, Rajan PK, Reeves H, Arcand C, Nakafuku Y, Joshi T, Finley R, Pierre SV, Sanabria JR. The Current Status of the Liver Liquid Biopsy in MASH Related HCC: Overview and Future Directions. Biomolecules 2023; 13:1369. [PMID: 37759769 PMCID: PMC10526956 DOI: 10.3390/biom13091369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/03/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is one of the major risk factors for chronic liver disease and hepatocellular carcinoma (HCC). The incidence of MASH in Western countries continues to rise, driving HCC as the third cause of cancer-related death worldwide. HCC has become a major global health challenge, partly from the obesity epidemic promoting metabolic cellular disturbances but also from the paucity of biomarkers for its early detection. Over 50% of HCC cases are clinically present at a late stage, where curative measures are no longer beneficial. Currently, there is a paucity of both specific and sensitive biological markers for the early-stage detection of HCC. The search for biological markers in the diagnosis of early HCC in high-risk populations is intense. We described the potential role of surrogates for a liver biopsy in the screening and monitoring of patients at risk for nesting HCC.
Collapse
Affiliation(s)
- Onyinye Ugonabo
- Department of Medicine, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (O.U.); (T.J.)
| | - Utibe-Abasi Sunday Udoh
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Pradeep Kumar Rajan
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Heather Reeves
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Christina Arcand
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Yuto Nakafuku
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Tejas Joshi
- Department of Medicine, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (O.U.); (T.J.)
| | - Rob Finley
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
| | - Sandrine V. Pierre
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
| | - Juan Ramon Sanabria
- Marshall Institute for Interdisciplinary Research, Marshall University School of Medicine, Huntington, WV 25703, USA; (U.-A.S.U.); (P.K.R.); (Y.N.); (S.V.P.)
- Department of Surgery, Marshall University School of Medicine, Marshall University, Huntington, WV 25701, USA; (H.R.); (C.A.); (R.F.)
- Department of Nutrition and Metabolomic Core Facility, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| |
Collapse
|
|
18
|
Yan R, Chen H, Selaru FM. Extracellular Vesicles in Hepatocellular Carcinoma: Progress and Challenges in the Translation from the Laboratory to Clinic. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1599. [PMID: 37763719 PMCID: PMC10534795 DOI: 10.3390/medicina59091599] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Revised: 08/27/2023] [Accepted: 08/31/2023] [Indexed: 09/29/2023]
Abstract
Extracellular vesicles (EVs) play critical roles in intercellular communication by transporting bioactive cargo to recipient cells. EVs have been implicated in a range of physiological and pathological processes, including tumor progression, metastasis, immune modulation, and drug resistance. The objective of this review is to present a thorough overview of recent studies focusing on EVs in hepatocellular carcinoma (HCC), with an emphasis on their potential utility as diagnostic biomarkers as well as therapeutic agents. Initially, we explore the utility of EVs as diagnostic biomarkers for HCC, followed by a discussion of their potential as carriers of therapeutic payloads. Additionally, we delve into the emerging field of therapeutic EVs for modulating tumor immune responses. Through this review, our ultimate aim is to provide a comprehensive understanding of the opportunities and challenges in the clinical translation of EV research in the domain of HCC.
Collapse
Affiliation(s)
- Rong Yan
- Department of Surgical Oncology, the First Affiliated Hospital, Xi’an Jiaotong University College of Medicine, Xi’an 710061, China
| | - Haiming Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
| | - Florin M. Selaru
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA;
- Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD 21224, USA
- The Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD 21231, USA
| |
Collapse
|
|
19
|
Peng Y, Gao Z, Qiao B, Li D, Pang H, Lai X, Pu Q, Zhang R, Zhao X, Zhao G, Xu D, Wang Y, Ji Y, Pei H, Wu Q. Size-Controlled DNA Tile Self-Assembly Nanostructures Through Caveolae-Mediated Endocytosis for Signal-Amplified Imaging of MicroRNAs in Living Cells. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2300614. [PMID: 37189216 PMCID: PMC10375201 DOI: 10.1002/advs.202300614] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 04/30/2023] [Indexed: 05/17/2023]
Abstract
Signal-amplified imaging of microRNAs (miRNAs) is a promising strategy at the single-cell level because liquid biopsy fails to reflect real-time dynamic miRNA levels. However, the internalization pathways for available conventional vectors predominantly involve endo-lysosomes, showing nonideal cytoplasmic delivery efficiency. In this study, size-controlled 9-tile nanoarrays are designed and constructed by integrating catalytic hairpin assembly (CHA) with DNA tile self-assembly technology to achieve caveolae-mediated endocytosis for the amplified imaging of miRNAs in a complex intracellular environment. Compared with classical CHA, the 9-tile nanoarrays possess high sensitivity and specificity for miRNAs, achieve excellent internalization efficiency by caveolar endocytosis, bypassing lysosomal traps, and exhibit more powerful signal-amplified imaging of intracellular miRNAs. Because of their excellent safety, physiological stability, and highly efficient cytoplasmic delivery, the 9-tile nanoarrays can realize real-time amplified monitoring of miRNAs in various tumor and identical cells of different periods, and imaging effects are consistent with the actual expression levels of miRNAs, ultimately demonstrating their feasibility and capacity. This strategy provides a high-potential delivery pathway for cell imaging and targeted delivery, simultaneously offering a meaningful reference for the application of DNA tile self-assembly technology in relevant fundamental research and medical diagnostics.
Collapse
Affiliation(s)
- Yanan Peng
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Zhijun Gao
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Bin Qiao
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
- Key Laboratory of Emergency and Trauma of Ministry of EducationResearch Unit of Island Emergency MedicineChinese Academy of Medical Sciences (No. 2019RU013)Hainan Medical UniversityHaikou571199P. R. China
| | - Dongxia Li
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Huajie Pang
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Xiangde Lai
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Qiumei Pu
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Rui Zhang
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Xuan Zhao
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Guangyuan Zhao
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Dan Xu
- Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of PharmacyHainan Medical UniversityHaikou571199P. R. China
| | - Yuanyuan Wang
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
- Key Laboratory of Emergency and Trauma of Ministry of EducationResearch Unit of Island Emergency MedicineChinese Academy of Medical Sciences (No. 2019RU013)Hainan Medical UniversityHaikou571199P. R. China
| | - Yuxiang Ji
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Hua Pei
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
| | - Qiang Wu
- The Second Affiliated HospitalSchool of Tropical MedicineHainan Medical UniversityHaikou571199P. R. China
- Key Laboratory of Emergency and Trauma of Ministry of EducationResearch Unit of Island Emergency MedicineChinese Academy of Medical Sciences (No. 2019RU013)Hainan Medical UniversityHaikou571199P. R. China
| |
Collapse
|
|
20
|
Huffman AM, Syed M, Rezq S, Anderson CD, Yanes Cardozo LL, Romero DG. Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice. Arch Toxicol 2023; 97:1907-1925. [PMID: 37179516 PMCID: PMC10919897 DOI: 10.1007/s00204-023-03499-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 04/17/2023] [Indexed: 05/15/2023]
Abstract
Acetaminophen (APAP)-induced Acute Liver Failure (ALF) is recognized as the most common cause of ALF in Western societies. APAP-induced ALF is characterized by coagulopathy, hepatic encephalopathy, multi-organ failure, and death. MicroRNAs are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. MicroRNA-21 (miR-21) is dynamically expressed in the liver and is involved in the pathophysiology of both acute and chronic liver injury models. We hypothesize that miR-21genetic ablation attenuates hepatotoxicity following acetaminophen intoxication. Eight-week old miR-21knockout (miR21KO) or wild-type (WT) C57BL/6N male mice were injected with acetaminophen (APAP, 300 mg/kg BW) or saline. Mice were sacrificed 6 or 24 h post-injection. MiR21KO mice presented attenuation of liver enzymes ALT, AST, LDH compared with WT mice 24 h post-APAP treatment. Moreover, miR21KO mice had decreased hepatic DNA fragmentation and necrosis than WT mice after 24 h of APAP treatment. APAP-treated miR21KO mice showed increased levels of cell cycle regulators CYCLIN D1 and PCNA, increased autophagy markers expression (Map1LC3a, Sqstm1) and protein (LC3AB II/I, p62), and an attenuation of the APAP-induced hypofibrinolytic state via (PAI-1) compared with WT mice 24 post-APAP treatment. MiR-21 inhibition could be a novel therapeutic approach to mitigate APAP-induced hepatotoxicity and enhance survival during the regenerative phase, particularly to alter regeneration, autophagy, and fibrinolysis. Specifically, miR-21 inhibition could be particularly useful when APAP intoxication is detected at its late stages and the only available therapy is minimally effective.
Collapse
Affiliation(s)
- Alexandra M Huffman
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA.
- Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
- Women's Health Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
- Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
| | - Maryam Syed
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA
- Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Women's Health Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Samar Rezq
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA
- Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Women's Health Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Christopher D Anderson
- Department of Surgery, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Licy L Yanes Cardozo
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Women's Health Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA
- Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA
| | - Damian G Romero
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA.
- Mississippi Center of Excellence in Perinatal Research, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
- Women's Health Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
- Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
| |
Collapse
|
|
21
|
Omar MA, Omran MM, Farid K, Tabll AA, Shahein YE, Emran TM, Petrovic A, Lucic NR, Smolic R, Kovac T, Smolic M. Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis. Biomedicines 2023; 11:1852. [PMID: 37509493 PMCID: PMC10377276 DOI: 10.3390/biomedicines11071852] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/15/2023] [Accepted: 06/21/2023] [Indexed: 07/30/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.
Collapse
Affiliation(s)
- Mona A. Omar
- Chemistry Department, Faculty of Science, Damietta University, New Damietta 34517, Egypt;
| | - Mohamed M. Omran
- Chemistry Department, Faculty of Science, Helwan University, Cairo 11795, Egypt;
| | - Khaled Farid
- Tropical Medicine Department, Faculty of Medicine, Mansoura University, Mansoura 35524, Egypt;
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, National Research Centre, Cairo 12622, Egypt
- Immunology Department, Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt
| | - Yasser E. Shahein
- Molecular Biology Department, National Research Centre, Cairo 12622, Egypt
| | - Tarek M. Emran
- Clinical Pathology Department, Faculty of Medicine, Al-Azhar University, New Damietta 34517, Egypt;
| | - Ana Petrovic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia; (A.P.); (N.R.L.); (R.S.); (T.K.)
| | - Nikola R. Lucic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia; (A.P.); (N.R.L.); (R.S.); (T.K.)
| | - Robert Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia; (A.P.); (N.R.L.); (R.S.); (T.K.)
| | - Tanja Kovac
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia; (A.P.); (N.R.L.); (R.S.); (T.K.)
| | - Martina Smolic
- Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia; (A.P.); (N.R.L.); (R.S.); (T.K.)
| |
Collapse
|
|
22
|
Lucarini V, Nardozi D, Angiolini V, Benvenuto M, Focaccetti C, Carrano R, Besharat ZM, Bei R, Masuelli L. Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion. Biomedicines 2023; 11:1761. [PMID: 37371856 DOI: 10.3390/biomedicines11061761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
Gastrointestinal (GI) cancers are the most frequent neoplasm, responsible for half of all cancer-related deaths. Metastasis is the leading cause of death from GI cancer; thus, studying the processes that regulate cancer cell migration is of paramount importance for the development of new therapeutic strategies. In this review, we summarize the mechanisms adopted by cancer cells to promote cell migration and the subsequent metastasis formation by highlighting the key role that tumor microenvironment components play in deregulating cellular pathways involved in these processes. We, therefore, provide an overview of the role of different microRNAs in promoting tumor metastasis and their role as potential biomarkers for the prognosis, monitoring, and diagnosis of GI cancer patients. Finally, we relate the possible use of nutraceuticals as a new strategy for targeting numerous microRNAs and different pathways involved in GI tumor invasiveness.
Collapse
Affiliation(s)
- Valeria Lucarini
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Daniela Nardozi
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Valentina Angiolini
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Monica Benvenuto
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
- Departmental Faculty of Medicine and Surgery, Saint Camillus International University of Health and Medical Sciences, via di Sant'Alessandro 8, 00131 Rome, Italy
| | - Chiara Focaccetti
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Raffaele Carrano
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Zein Mersini Besharat
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| | - Roberto Bei
- Department of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Laura Masuelli
- Department of Experimental Medicine, University of Rome "Sapienza", Viale Regina Elena 324, 00161 Rome, Italy
| |
Collapse
|
|
23
|
Cao X, Dong J, Sun R, Zhang X, Chen C, Zhu Q. A DNAzyme-enhanced nonlinear hybridization chain reaction for sensitive detection of microRNA. J Biol Chem 2023; 299:104751. [PMID: 37100287 DOI: 10.1016/j.jbc.2023.104751] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 04/17/2023] [Accepted: 04/20/2023] [Indexed: 04/28/2023] Open
Abstract
As a typical biomarker, the expression of microRNA is closely related to the occurrence of cancer. However, in recent years, the detection methods have had some limitations in the research and application of microRNAs. In this paper, an autocatalytic platform was constructed through the combination of a nonlinear hybridization chain reaction and DNAzyme to achieve efficient detection of microRNA-21. Fluorescently labeled fuel probes can form branched nanostructures and new DNAzyme under the action of the target, and the newly formed DNAzyme can trigger a new round of reactions, resulting in enhanced fluorescence signals. This platform is a simple, efficient, fast, low-cost, and selective method for the detection of microRNA-21, which can detect microRNA-21 at concentrations as low as 0.004 nM and can distinguish sequence differences by single-base differences. In tissue samples from liver cancer patients, the platform shows the same detection accuracy as real-time PCR but with better reproducibility. In addition, through the flexible design of the trigger chain, our method could be adapted to detect other nucleic acids biomarkers.
Collapse
Affiliation(s)
- Xiuen Cao
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
| | - Jiani Dong
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China
| | - Ruowei Sun
- Hunan Zaochen Nanorobot Co. Ltd, Liuyang 410300, Hunan, China
| | - Xun Zhang
- Hunan Zaochen Nanorobot Co. Ltd, Liuyang 410300, Hunan, China
| | - Chuanpin Chen
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China.
| | - Qubo Zhu
- Xiangya School of Pharmaceutical Sciences in Central South University, Changsha 410013, Hunan, China.
| |
Collapse
|
|
24
|
Wu ZQ, Zhu YX, Jin Y, Zhan YC. Exosomal miRNA in early-stage hepatocellular carcinoma. World J Clin Cases 2023; 11:528-533. [PMID: 36793641 PMCID: PMC9923864 DOI: 10.12998/wjcc.v11.i3.528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/26/2022] [Accepted: 01/05/2023] [Indexed: 01/23/2023] Open
Abstract
The incidence and mortality of hepatic carcinoma (HCC) remain high, and early diagnosis of HCC is seen as a key approach in improving clinical outcomes. However, the sensitivity and specificity of current early screening methods for HCC are not satisfactory. In recent years, research around exosomal miRNA has gradually increased, and these molecules have emerged as attractive candidates for early diagnosis and treatment of HCC. This review summarizes the feasibility of using miRNAs in peripheral blood exosomes as early diagnostic tools for HCC.
Collapse
Affiliation(s)
- Zhi-Qiang Wu
- Department of Surgery, The Second People's Hosptal of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Yi-Xin Zhu
- Department of Surgery, The Second People's Hosptal of Quzhou, Quzhou 324000, Zhejiang Province, China
| | - Yun Jin
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Yin-Chu Zhan
- Department of Surgery, The Second People's Hosptal of Quzhou, Quzhou 324000, Zhejiang Province, China
| |
Collapse
|
|
25
|
Rana M, Saini M, Das R, Gupta S, Joshi T, Mehta DK. Circulating MicroRNAs: Diagnostic Value as Biomarkers in the Detection of Non-alcoholic Fatty Liver Diseases and Hepatocellular Carcinoma. Microrna 2023; 12:99-113. [PMID: 37005546 DOI: 10.2174/2211536612666230330083146] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 01/09/2023] [Accepted: 01/20/2023] [Indexed: 04/04/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD), a metabolic-related disorder, is the most common cause of chronic liver disease which, if left untreated, can progress from simple steatosis to advanced fibrosis and eventually cirrhosis or hepatocellular carcinoma, which is the leading cause of hepatic damage globally. Currently available diagnostic modalities for NAFLD and hepatocellular carcinoma are mostly invasive and of limited precision. A liver biopsy is the most widely used diagnostic tool for hepatic disease. But due to its invasive procedure, it is not practicable for mass screening. Thus, noninvasive biomarkers are needed to diagnose NAFLD and HCC, monitor disease progression, and determine treatment response. Various studies indicated that serum miRNAs could serve as noninvasive biomarkers for both NAFLD and HCC diagnosis because of their association with different histological features of the disease. Although microRNAs are promising and clinically useful biomarkers for hepatic diseases, larger standardization procedures and studies are still required.
Collapse
Affiliation(s)
- Minakshi Rana
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Manisha Saini
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Rina Das
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Sumeet Gupta
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Tanishq Joshi
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| | - Dinesh Kumar Mehta
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala, HR, India
| |
Collapse
|
|
26
|
El-Daly SM, Gouhar SA, Abd Elmageed ZY. Circulating microRNAs as Reliable Tumor Biomarkers: Opportunities and Challenges Facing Clinical Application. J Pharmacol Exp Ther 2023; 384:35-51. [PMID: 35809898 PMCID: PMC9827506 DOI: 10.1124/jpet.121.000896] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 06/23/2022] [Accepted: 06/24/2022] [Indexed: 01/13/2023] Open
Abstract
MicroRNAs (miRNAs) are involved in the development of human malignancies, and cells have the ability to secrete these molecules into extracellular compartments. Thus, cell-free miRNAs (circulating miRNAs) can potentially be used as biomarkers to evaluate pathophysiological changes. Although circulating miRNAs have been proposed as potential noninvasive tumor biomarkers for diagnosis, prognosis, and response to therapy, their routine application in the clinic is far from being achieved. This review focuses on the recent progress regarding the value of circulating miRNAs as noninvasive biomarkers, with specific consideration of their relevant clinical applications. In addition, we provide an in-depth analysis of the technical challenges that impact the assessment of circulating miRNAs. We also highlight the significance of integrating circulating miRNAs with the standard laboratory biomarkers to boost sensitivity and specificity. The current status of circulating miRNAs in clinical trials as tumor biomarkers is also covered. These insights and general guidelines will assist researchers in experimental practice to ensure quality standards and repeatability, thus improving future studies on circulating miRNAs. SIGNIFICANCE STATEMENT: Our review will boost the knowledge behind the inconsistencies and contradictory results observed among studies investigating circulating miRNAs. It will also provide a solid platform for better-planned strategies and standardized techniques to optimize the assessment of circulating cell-free miRNAs.
Collapse
Affiliation(s)
- Sherien M El-Daly
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Cairo, Egypt (S.M.E-D., S.A.G.); Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt (S.M.E-D.); and Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana-Monroe, Monroe, Louisiana (Z.Y.A.)
| | - Shaimaa A Gouhar
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Cairo, Egypt (S.M.E-D., S.A.G.); Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt (S.M.E-D.); and Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana-Monroe, Monroe, Louisiana (Z.Y.A.)
| | - Zakaria Y Abd Elmageed
- Medical Biochemistry Department, Medicine and Clinical Studies Research Institute, National Research Centre, Dokki, Cairo, Egypt (S.M.E-D., S.A.G.); Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Cairo, Egypt (S.M.E-D.); and Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana-Monroe, Monroe, Louisiana (Z.Y.A.)
| |
Collapse
|
|
27
|
Abdel Halim AS, Rudayni HA, Chaudhary AA, Ali MAM. MicroRNAs: Small molecules with big impacts in liver injury. J Cell Physiol 2023; 238:32-69. [PMID: 36317692 DOI: 10.1002/jcp.30908] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/30/2022] [Accepted: 10/14/2022] [Indexed: 11/07/2022]
Abstract
A type of small noncoding RNAs known as microRNAs (miRNAs) fine-tune gene expression posttranscriptionally by binding to certain messenger RNA targets. Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells. The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNA-mediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver-specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.
Collapse
Affiliation(s)
- Alyaa S Abdel Halim
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hassan Ahmed Rudayni
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Anis Ahmad Chaudhary
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Mohamed A M Ali
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.,Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| |
Collapse
|
|
28
|
Hussein MA, Radwan AFM, Fawzi MM, Rashed LA, Saad EHAI. MicroRNA 21as a novel biomarker in hepatitis C virus-related hepatocellular carcinoma. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00136-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Hepatocellular carcinoma is considered one of the most common cancers occurring in human population all over the world. It became an increasingly threatening malignancy due to both morbidity and mortality. Chronic viral hepatitis B and hepatitis C are two risk factors, which account for 80–90% of all HCC cases worldwide. Alfa Feto protien is used as a tumor marker for HCC diagnosis and prognosis prediction; however, its false negative rate when used alone is as high as 40% for patients with early-stage HCC. AFP levels remain normal in 15–30% of all the patients, even patients with advanced HCC. It has been demonstrated that miRNAs (MicroRNAs) are an important class of non-coding RNAs. They act as tumor oncogenes or suppressors and are involved in the HCC development. MiRNAs are endogenous nucleotides that can be found in intra- and extracellular spaces, such as the blood, urine, and saliva.
The study evaluated the miRNA 21 as a novel biomarker in patients with HCV related hepatocellular carcinoma.
Results
The study was conducted on three groups. Group (1) included 25 patients with liver cirrhosis due to hepatitis C virus infection. Group (2) included 25 patients with hepatocellular carcinoma (HCC) on top of liver cirrhosis due to hepatitis C virus infection. Group (3) included 10 normal control subjects. There was a significant difference in the mean level of miRNA between the three groups with p value < 0.001 with the highest value in group 2 ( 8.28 ± 2.55), then in group1 (5.04 ± 2.11) and the lowest in group 3 (control) (1.02 ± 0.07). MiRNA 21 has a sensitivity of 68% and a specificity of 96%, to differentiate between the liver cirrhosis group and HCC group.
Conclusion
miRNA 21 can be a promising marker for detection of patients with HCV-related hepatocellular carcinoma, with higher specificity compared to α feto protein; however, its cost is higher.
Collapse
|
|
29
|
da Silva Freire AK, Furtado de Mendonça Belmont T, Pinto Santiago EJ, Cristina Cordeiro Farias I, Palmeira do Ó K, Soares da Silva A, Richardson Silva Vasconcelos L. Potential role of circulating miR-21 in the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Expert Rev Mol Diagn 2022; 22:1037-1052. [PMID: 36348568 DOI: 10.1080/14737159.2022.2145189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Identify original articles that analyzed the diagnostic value of miR-21 in hepatocellular carcinoma without language restriction or publication date. METHODOLOGY We performed structured searches on PubMed, Web of Science, VHL, and EMBASE. The Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields was used to assess the quality of each study. Random effect models were used to study heterogeneity, evaluated based on the Higgins I2 statistic. RESULTS 12 articles were evaluated and contained raw data from 1,329 individuals, of which 617 had HCC, 473 were healthy, and 239 had Chronic liver disease. The combined sensitivity and combined specificity of miR-21 for diagnosing HCC were, respectively, 0.83(95% CI:0.78-0.89) and 0.85(95% CI:0.80-0.90). The sensitivity and specificity, in that order, by type of control were 0.81 (95% CI: 0.71-0.91) and 0.88 (95% CI: 0.82-0.93) for CLDs and 0.86(95% CI: 0.81-0.91) and 0.83(95% CI:0.74-0.91) for Healthy controls. CONCLUSION miR-21 has a moderate overall performance in diagnosing HCC and may serve as a potential non-invasive marker for this early-stage disease. Thus, it may contribute to complementing the results of alpha-fetoprotein in the diagnosis and help to detect HCC at an earlier stage, increasing the survival chances of these patients.
Collapse
Affiliation(s)
| | - Taciana Furtado de Mendonça Belmont
- Postgraduate Program in Health Sciences, University of Pernambuco (UPE), Recife, Brazil.,Department of Parasitology, Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz (FIOCRUZ), Recife, Brazil
| | - Edgo Jackson Pinto Santiago
- Postgraduate Program in Biometrics and Applied Statistics, University Federal Rural de Pernambuco (UFRPE), Recife, Brazil
| | | | - Kleyton Palmeira do Ó
- Department of Parasitology, Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz (FIOCRUZ), Recife, Brazil
| | - Andreia Soares da Silva
- Department of Parasitology, Institute Aggeu Magalhães (IAM), Foundation Oswaldo Cruz (FIOCRUZ), Recife, Brazil
| | | |
Collapse
|
|
30
|
Combination of Circulating miR-125a-5p, miR-223-3p and D-dimer as a Novel Biomarker for Deep Vein Thrombosis. Am J Med Sci 2022; 364:601-611. [PMID: 35588895 DOI: 10.1016/j.amjms.2022.04.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 11/19/2021] [Accepted: 04/08/2022] [Indexed: 01/25/2023]
Abstract
BACKGROUND Deep venous thrombosis (DVT) is a thrombus formed in the deep venous cavity and can cause a fatal pulmonary embolism. Since circulating miRNAs are used as molecular markers for the early warning and diagnosis of various diseases, such as tumors and cardiovascular diseases, the purpose of the present study was initially to identify differential expression circulating miRNAs in plasma, and then explore potential biomarkers for DVT. METHODS The plasma of 30 patients with DVT before and after DVT-related endovascular interventions constituted 6 sample pools for miRNA sequencing, and the levels of 22 plasma miRNAs were significantly changed. Then, various bioinformatics tools were utilized to screen out 8 miRNAs with potential DVT diagnostic value. Furthermore, their diagnostic values were evaluated in 120 patients with DVT and 120 healthy individuals. RESULTS The levels of 22 circulating plasma miRNAs (12 up-regulated, 10 down-regulated) were significantly changed in patients with DVT before and after endovascular interventions, especially miR-125a-5p (up-regulation) and miR-223-3p (down-regulation). The values of area under the ROC curve (AUC) of miR-125a-5p and miR-223-3p were both >0.8, indicating that they were valuable in diagnosing DVT. The combination of miR-125a-5p and miR-223-3p with D-dimer significantly improved the efficiency of diagnosing DVT, (AUC >0.97, the sensitivity and specificity >95%), and was better than those of D-dimer alone. CONCLUSIONS The levels of miR-125a-5p and miR-223-3p were the most significantly changed in patients with DVT before and after endovascular interventions; together with the classic biomarker D-dimer, they can be used as a potential biomarker for diagnostic and therapeutic process of DVT.
Collapse
|
|
31
|
Han Q, Wang M, Dong X, Wei F, Luo Y, Sun X. Non-coding RNAs in hepatocellular carcinoma: Insights into regulatory mechanisms, clinical significance, and therapeutic potential. Front Immunol 2022; 13:985815. [PMID: 36300115 PMCID: PMC9590653 DOI: 10.3389/fimmu.2022.985815] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a complex and heterogeneous malignancy with high incidence and poor prognosis. In addition, owing to the lack of diagnostic and prognostic markers, current multimodal treatment options fail to achieve satisfactory outcomes. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transition (EMT), invasion, metastasis, metabolism, and drug resistance are important factors influencing tumor development and therapy. The intercellular communication of these important processes is mediated by a variety of bioactive molecules to regulate pathophysiological processes in recipient cells. Among these bioactive molecules, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), account for a large part of the human transcriptome, and their dysregulation affects the progression of HCC. The purpose of this review is to evaluate the potential regulatory mechanisms of ncRNAs in HCC, summarize novel biomarkers from somatic fluids (plasma/serum/urine), and explore the potential of some small-molecule modulators as drugs. Thus, through this review, we aim to contribute to a deeper understanding of the regulatory mechanisms, early diagnosis, prognosis, and precise treatment of HCC.
Collapse
Affiliation(s)
- Qin Han
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory for Research and Evaluation of Pharmacovigilance, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Mengchen Wang
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory for Research and Evaluation of Pharmacovigilance, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xi Dong
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory for Research and Evaluation of Pharmacovigilance, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Fei Wei
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory for Research and Evaluation of Pharmacovigilance, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yun Luo
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory for Research and Evaluation of Pharmacovigilance, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Yun Luo, ; Xiaobo Sun,
| | - Xiaobo Sun
- Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory for Research and Evaluation of Pharmacovigilance, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Yun Luo, ; Xiaobo Sun,
| |
Collapse
|
|
32
|
Chen T. Circulating Non-Coding RNAs as Potential Diagnostic Biomarkers in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:1029-1040. [PMID: 36132427 PMCID: PMC9484560 DOI: 10.2147/jhc.s380237] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/06/2022] [Indexed: 11/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is currently the second leading cause of cancer-related deaths worldwide, with high morbidity and mortality. The clinical diagnosis of HCC mainly depends on imaging technology, such as ultrasound and computed tomography, and serum biomarkers, such as alpha-fetoprotein (AFP). However, HCC is still hard to diagnose at an early stage due to the low sensitivity of the above mentioned traditional methods. Typically, HCC is diagnosed at an advanced stage when limited treatment options are available. It is urgent to identify effective biomarkers for the early diagnosis of HCC. Increasing evidence uncovered ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), could be used in HCC diagnosis. The aim of this review is to summarize our understanding of circulating miRNAs, lncRNAs and circRNAs as fluid-based non-invasive biomarkers, and aiming at providing new insights into the diagnosis of HCC.
Collapse
Affiliation(s)
- Tingsong Chen
- The Second Department of Oncology, the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
| |
Collapse
|
|
33
|
Exosomes and cancer - Diagnostic and prognostic biomarkers and therapeutic vehicle. Oncogenesis 2022; 11:54. [PMID: 36109501 PMCID: PMC9477829 DOI: 10.1038/s41389-022-00431-5] [Citation(s) in RCA: 112] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 08/24/2022] [Accepted: 08/26/2022] [Indexed: 11/08/2022] Open
Abstract
AbstractExosomes belong to a subpopulation of extracellular vesicles secreted by the dynamic multistep endocytosis process and carry diverse functional molecular cargoes, including proteins, lipids, nucleic acids (DNA, messenger and noncoding RNA), and metabolites to promote intercellular communication. Proteins and noncoding RNA are among the most abundant contents in exosomes; they have biological functions and are selectively packaged into exosomes. Exosomes derived from tumor, stromal and immune cells contribute to the multiple stages of cancer progression as well as resistance to therapy. In this review, we will discuss the biogenesis of exosomes and their roles in cancer development. Since specific contents within exosomes originate from their cells of origin, this property allows exosomes to function as valuable biomarkers. We will also discuss the potential use of exosomes as diagnostic and prognostic biomarkers or predictors for different therapeutic strategies for multiple cancers. Furthermore, the applications of exosomes as direct therapeutic targets or engineered vehicles for drugs are an important field of exosome study. Better understanding of exosome biology may pave the way to promising exosome-based clinical applications.
Collapse
|
|
34
|
Rhim J, Baek W, Seo Y, Kim JH. From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells 2022; 11:cells11182791. [PMID: 36139366 PMCID: PMC9497241 DOI: 10.3390/cells11182791] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/29/2022] Open
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in regulating gene expression at a posttranscriptional level. As one of the first discovered oncogenic miRNAs, microRNA-21 (miR-21) has been highlighted for its critical role in cancers, such as glioblastoma, pancreatic adenocarcinoma, non-small cell lung cancer, and many others. MiR-21 targets many vital components in a wide range of cancers and acts on various cellular processes ranging from cancer stemness to cell death. Expression of miR-21 is elevated within cancer tissues and circulating miR-21 is readily detectable in biofluids, making it valuable as a cancer biomarker with significant potential for use in diagnosis and prognosis. Advances in RNA-based therapeutics have revealed additional avenues by which miR-21 can be utilized as a promising target in cancer. The purpose of this review is to outline the roles of miR-21 as a key modulator in various cancers and its potential as a therapeutic target.
Collapse
Affiliation(s)
- Jiho Rhim
- Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Korea
- Department of Cancer Biomedical Science, National Cancer Center, Graduate School of Cancer Science and Policy, Goyang 10408, Korea
| | - Woosun Baek
- Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Korea
- Department of Cancer Biomedical Science, National Cancer Center, Graduate School of Cancer Science and Policy, Goyang 10408, Korea
| | - Yoona Seo
- Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Korea
- Department of Cancer Biomedical Science, National Cancer Center, Graduate School of Cancer Science and Policy, Goyang 10408, Korea
| | - Jong Heon Kim
- Cancer Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Korea
- Department of Cancer Biomedical Science, National Cancer Center, Graduate School of Cancer Science and Policy, Goyang 10408, Korea
- Correspondence: ; Tel.: +82-31-920-2204
| |
Collapse
|
|
35
|
Target-initiated DNA release-directed catalytic hairpin assembly-based ultrasensitive cyclic amplification sensor detection of serum miRNA. Anal Chim Acta 2022; 1232:340437. [DOI: 10.1016/j.aca.2022.340437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 09/12/2022] [Accepted: 09/22/2022] [Indexed: 11/18/2022]
|
|
36
|
Aksoy F, Ak Aksoy S, Dundar HZ, Tunca B, Ercelik M, Tekin Ç, Kıyıcı M, Selimoglu K, Kaya E. Blood-Based Biomarkers in Afp Normal/Stable Hepatocellular Carcinoma: Diagnostic and Prognostic Relevance of Mir-10b for Patients on Liver Transplant List. Transplant Proc 2022; 54:1826-1833. [PMID: 35987859 DOI: 10.1016/j.transproceed.2022.05.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 03/22/2022] [Accepted: 05/22/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND As a diagnostic criteria of hepatocellular carcinoma (HCC), the exact threshold of alpha-fetoprotein (AFP) is controversial. In additional, not all HCC tumors are AFP positive or secrete elevated amounts of AFP into the serum. However, the diagnosis of HCC is quite important on the liver transplant list. Therefore, the purpose of this study was to investigate the expression of circulating micro RNAs (miRNAs) in AFP-stable HCC patients. Thus, we aimed to determine a diagnostic biomarker in these patients. METHODS Sixteen miRNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction system in AFP-stable HCC and AFP-trending HCC patients. RESULTS In our study, 46.7% (n = 28) of the patients diagnosed with HCC had stable/normal AFP levels. We detected that high expression of miR-24, miR-10b and the low expression of miR-143 were independently and significantly associated with HCC in AFP-stable compared with AFP trending (P < .05). Additionally, we demonstrated that the overexpression of miR-10b was associated with poor disease-free survival in HCC (P = 0.001). CONCLUSIONS Although more clinical validations are needed for the diagnosis of HCC, our current results indicate that the coexistence of high expression of miR-10b and miR-24 may help clinicians adjust in the diagnosis of HCC in patients who are on the liver transplant list but awaiting biopsy for the diagnosis of HCC.
Collapse
Affiliation(s)
- Fuat Aksoy
- Organ Transplantation Center, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| | - Secil Ak Aksoy
- Inegol Vocation School, Bursa Uludag University, Inegol, Bursa, Turkey
| | - Halit Ziya Dundar
- Organ Transplantation Center, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.
| | - Berrin Tunca
- Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| | - Melis Ercelik
- Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| | - Çagla Tekin
- Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| | - Murat Kıyıcı
- Department of Gastroenterology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| | - Kerem Selimoglu
- Organ Transplantation Center, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| | - Ekrem Kaya
- Organ Transplantation Center, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| |
Collapse
|
|
37
|
Khan S, Zhang DY, Zhang JY, Hayat MK, Ren J, Nasir S, Fawad M, Bai Q. The Key Role of microRNAs in Initiation and Progression of Hepatocellular Carcinoma. Front Oncol 2022; 12:950374. [PMID: 35924150 PMCID: PMC9341471 DOI: 10.3389/fonc.2022.950374] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 06/01/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the main type of primary liver malignancy and the fourth leading cause of cancer-related death worldwide. MicroRNAs (miRNAs), a type of non-coding RNA that regulates gene expression mainly on post-transcriptional level has a confirmed and important role in numerous biological process. By regulating specific target genes, miRNA can act as oncogene or tumor suppressor. Recent evidence has indicated that the deregulation of miR-NAs is closely associated with the clinical pathological features of HCC. However, the precise regulatory mechanism of each miRNA and its targets in HCC has yet to be illuminated. This study demonstrates that both oncogenic and tumor suppressive miRNAs are crucial in the formation and development of HCC. miRNAs influence biological behavior including proliferation, invasion, metastasis and apoptosis by targeting critical genes. Here, we summarize current knowledge about the expression profile and function of miRNAs in HCC and discuss the potential for miRNA-based therapy for HCC.
Collapse
Affiliation(s)
- Suliman Khan
- Department of Cerebrovascular Diseases, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - De-Yu Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ji-Yu Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mian Khizar Hayat
- Ministry of Education (MOE) Key Laboratory of Cell Activities and Stress Adopations, School of Life Sciences, Lanzhou University, Lanzhou, China
| | - Jingli Ren
- Zhengzhou Key Laboratory of Big Data Analysis and Application, Henan Academy of Big Data, Zhengzhou University, Zhengzhou, China
| | - Safyan Nasir
- Allied District Headquarter Hospital, Faisalabad, Pakistan
| | - Muhammad Fawad
- Zhengzhou Key Laboratory of Big Data Analysis and Application, Henan Academy of Big Data, Zhengzhou University, Zhengzhou, China
- School of Mathematics and Statistics, Zhengzhou University, Zhengzhou, China
- *Correspondence: Muhammad Fawad, ; Qian Bai,
| | - Qian Bai
- Department of Cerebrovascular Diseases, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Muhammad Fawad, ; Qian Bai,
| |
Collapse
|
|
38
|
Yu G, Mu H, Fang F, Zhou H, Li H, Wu Q, Xiong Q, Cui Y. LRP1B mutation associates with increased tumor mutation burden and inferior prognosis in liver hepatocellular carcinoma. Medicine (Baltimore) 2022; 101:e29763. [PMID: 35777027 PMCID: PMC9239668 DOI: 10.1097/md.0000000000029763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Liver hepatocellular carcinoma (LIHC) is the most common primary liver cancer and the main cause of death in patients with cirrhosis. LRP1B is found to involve in a variety of cancers, but the association of LRP1B mutation with tumor mutation burden (TMB) and prognosis of LIHC is rarely studied. METHODS AND RESULTS Herein, we analyzed the somatic mutation data of 364 LIHC patients from The Cancer Genome Atlas (TCGA) and found that LRP1B showed elevated mutation rate. Calculation of the TMB in LRP1B mutant and LRP1B wild-type groups showed that LRP1B mutant group had higher TMB compared with that in LRP1B wild-type group. Then survival analysis was performed and the survival curve showed that LRP1B mutation was associated with poor survival outcome, and this association remained to be significant after adjusting for multiple confounding factors including age, gender, tumor stage, mutations of BRCA1, BRCA2, and POLE. CONCLUSION Collectively, our results revealed that LRP1B mutation was related to high TMB value and poor prognosis in LIHC, indicating that LRP1B mutation is probably helpful for the selection of immunotherapy and prognosis prediction in LIHC.
Collapse
Affiliation(s)
- Ge Yu
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Han Mu
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Feng Fang
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Hongyuan Zhou
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Huikai Li
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Qiang Wu
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Qingqing Xiong
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
| | - Yunlong Cui
- Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin, China
- *Correspondence: Yunlong Cui, Department of Hepatobiliary Cancer, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, PR China (e-mail: )
| |
Collapse
|
|
39
|
A Target-Feedback Rolling-Cleavage Signal Amplifier for Ultrasensitive Electrochemical Detection of miRNA with Self-Assembled CeO2@Ag Hybrid Nanoflowers. Bioelectrochemistry 2022; 146:108152. [DOI: 10.1016/j.bioelechem.2022.108152] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/30/2022] [Accepted: 04/30/2022] [Indexed: 01/15/2023]
|
|
40
|
The diagnostic utility of microRNA 222-3p, microRNA 21-5p, and microRNA 122-5p for HCV-related hepatocellular carcinoma and its relation to direct-acting antiviral therapy. Arab J Gastroenterol 2022; 23:108-114. [DOI: 10.1016/j.ajg.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/22/2022] [Accepted: 04/11/2022] [Indexed: 11/21/2022]
|
|
41
|
El-Mahdy HA, Sallam AAM, Ismail A, Elkhawaga SY, Elrebehy MA, Doghish AS. miRNAs inspirations in hepatocellular carcinoma: Detrimental and favorable aspects of key performers. Pathol Res Pract 2022; 233:153886. [PMID: 35405621 DOI: 10.1016/j.prp.2022.153886] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/23/2022] [Accepted: 04/01/2022] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. HCC initiation, progression, and therapy failure are all influenced by various variables, including microRNAs (miRNAs). miRNAs are short non-coding RNA sequences that modulate target mRNA expression by deteriorating or repressing translation. miRNAs play an imperative role in HCC pathogenesis by triggering the induction of cancer stem cells (CSCs) and their proliferation, while also delaying apoptosis, sustaining the cell cycle, and inspiring angiogenesis, invasion, and metastasis. Additionally, miRNAs modulate crucial HCC-related molecular pathways such as the p53 pathway, the Wnt/β-catenin pathway, VEGFR2, and PTEN/PI3K/AKT pathway. Consequently, the goal of this review was to give an up-to-date overview of oncogenic and tumor suppressor (TS) miRNAs, as well as their potential significance in HCC pathogenesis and treatment responses, highlighting their underpinning molecular pathways in HCC initiation and progression. Similarly, the biological importance and clinical application of miRNAs in HCC are summarized.
Collapse
Affiliation(s)
- Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Al-Aliaa M Sallam
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Samy Y Elkhawaga
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Mahmoud A Elrebehy
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt.
| |
Collapse
|
|
42
|
Chen F, Wang J, Wu Y, Gao Q, Zhang S. Potential Biomarkers for Liver Cancer Diagnosis Based on Multi-Omics Strategy. Front Oncol 2022; 12:822449. [PMID: 35186756 PMCID: PMC8851237 DOI: 10.3389/fonc.2022.822449] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/17/2022] [Indexed: 12/11/2022] Open
Abstract
Liver cancer is the fourth leading cause of cancer-related death worldwide. Hepatocellular carcinoma (HCC) accounts for about 85%-90% of all primary liver malignancies. However, only 20-30% of HCC patients are eligible for curative therapy mainly due to the lack of early-detection strategies, highlighting the significance of reliable and accurate biomarkers. The integration of multi-omics became an important tool for biomarker screening and unique alterations in tumor-associated genes, transcripts, proteins, post-translational modifications and metabolites have been observed. We here summarized the novel biomarkers for HCC diagnosis based on multi-omics technology as well as the clinical significance of these potential biomarkers in the early detection of HCC.
Collapse
Affiliation(s)
- Fanghua Chen
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Junming Wang
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Yingcheng Wu
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Qiang Gao
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
| | - Shu Zhang
- Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
- Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
- *Correspondence: Shu Zhang,
| |
Collapse
|
|
43
|
Long J, Liu B, Yao Z, Weng H, Li H, Jiang C, Fang S. miR-500a-3p is a Potential Prognostic Biomarker in Hepatocellular Carcinoma. Int J Gen Med 2022; 15:1891-1899. [PMID: 35221718 PMCID: PMC8881010 DOI: 10.2147/ijgm.s340629] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/21/2022] [Indexed: 12/27/2022] Open
Abstract
Purpose miR-500a-3p has been extensively reported to be implicated in the development and progression in several human cancer types. This study aimed to investigate the diagnostic and prognostic significance of miR-500a-3p as a biomarker in hepatocellular carcinoma (HCC). Methods miR-500a-3p expression was evaluated by in situ hybridization (ISH) and real-time PCR in 10 adjacent normal tissues (ANT), 21 liver fibrosis tissues, and 110 HCC tissues. Statistical analysis was used to investigate the correlation of miR-500a-3p expression with clinicopathological features in HCC patients. Kaplan–Meier survival analysis was performed to evaluate the prognostic significance of miR-500a-3p in overall survival and recurrence-free survival in HCC patients. Results In this study, we found that expression levels of miR-500a-3p were enhanced in HCC tissues. High miR-500a-3p levels were positively correlated with multiple clinicopathological features, including advanced clinical stage, distant metastatic status, increased AFP levels and poor tumor differentiation degree. More importantly, high miR-500a-3p levels predicted poor overall survival and early recurrence in HCC patients. Finally, a strong and positive correlation of miR-500a-3p mRNA expression with ISH staining scores was observed in clinical HCC tissues. Conclusion Our findings suggest that miR-500a-3p might be used as a novel biomarker to facilitate early diagnosis and predict prognosis in HCC patients.
Collapse
Affiliation(s)
- Jianting Long
- Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| | - Baoxian Liu
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| | - Zhijia Yao
- Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| | - Huiwen Weng
- Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| | - Heping Li
- Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| | - Chunlin Jiang
- Department of General Surgery, Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China
- Guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery, Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China
- Correspondence: Chunlin Jiang, Email
| | - Shi Fang
- Department of Clinical Nutrition, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| |
Collapse
|
|
44
|
Chen S, Zhao J, Sakharov IY, Xu J, Xu C, Zhao S. An ultrasensitive multivariate signal amplification strategy based on microchip platform tailored for simultaneous quantification of multiple microRNAs in single cell. Biosens Bioelectron 2022; 203:114053. [PMID: 35121443 DOI: 10.1016/j.bios.2022.114053] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 01/27/2022] [Indexed: 12/13/2022]
Abstract
MicroRNAs (miRNAs) play a very important regulatory role in life activities. Abnormal expression levels of miRNAs in cells are associated with various diseases, especially human cancer. Nevertheless, accurate detection of the copy numbers of various miRNA molecules in single cell is still a great challenge. In this study, an intracellular multivariate signal amplification strategy based on microchip platform was proposed, and an ultrasensitive single-cell analysis method was established for simultaneous quantification of absolute copy numbers of multiple miRNAs in a single cell. Using miRNA-21 and miRNA-141 as the analytical models of miRNAs, the detection limits of 1.0 and 2.0 fM were obtained. Based on the developed method, an analysis of 600 randomly acquired different types of cells was performed. The distribution of absolute copy numbers of miRNA-21 and miRNA-141 in six types of cells was obtained. It was found that the number of copies of miRNA-21 and miRNA-141 in different types of cancer cells showed different expression characteristics. The study results can help us more accurately understand cell-to-cell heterogeneity and the relationship between different miRNAs and different types of cancer at the single cell level.
Collapse
Affiliation(s)
- Shengyu Chen
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, China
| | - Jingjin Zhao
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, China.
| | - Ivan Yu Sakharov
- Department of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia
| | - Jiayao Xu
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, China
| | - Chunhuan Xu
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, China
| | - Shulin Zhao
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, China.
| |
Collapse
|
|
45
|
Valente M, Covre A, Giacomo AMD, Maio M. Personalized Medicine for Patients with Liver, Biliary Tract, and Pancreatic Cancer. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:761-776. [DOI: 10.1007/978-3-030-41683-6_50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
46
|
Wang H, Hu Z, Sukumar UK, Bose RJC, Telichko A, Dahl JJ, Paulmurugan R. Ultrasound-Guided Microbubble-Mediated Locoregional Delivery of Multiple MicroRNAs Improves Chemotherapy in Hepatocellular Carcinoma. Nanotheranostics 2022; 6:62-78. [PMID: 34976581 PMCID: PMC8671967 DOI: 10.7150/ntno.63320] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 08/19/2021] [Indexed: 12/11/2022] Open
Abstract
Rationale: To assess treatment effects of 4 complementary miRNAs (miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21) encapsulated in a biodegradable PLGA-PEG nanoparticle, administered by an ultrasound-guided microbubble-mediated targeted delivery (UGMMTD) approach in mouse models of hepatocellular carcinoma (HCC). Methods:In vitro apoptotic index was measured in HepG2 and Hepa1-6 HCC cells treated with various combinations of the 4 miRNAs with doxorubicin. Three promising combinations were further tested in vivo by using UGMMTD. 63 HepG2 xenografts in mice were randomized into: group 1, miRNA-122/antimiRNA-10b/antimiRNA-21/US/doxorubicin; group 2, miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21/US/doxorubicin; group 3, miRNA-100/miRNA-122/antimiRNA-10b/US/doxorubicin; group 4, miRNA-122/anitmiRNA-10b/antimiRNA-21/doxorubicin; group 5, miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21/doxorubicin; group 6, miRNA-100/miRNA-122/antimiRNA-10b/doxorubicin; group 7, doxorubicin only treatment; and group 8, without any treatment. Tumor volumes were measured through 18 days. H&E staining, TUNEL assay, and qRT-PCR quantification for delivered miRNAs were performed. Results:In vivo results showed that UGMMTD of miRNAs with doxorubicin in groups 1-3 significantly (P<0.05) delayed tumor growth compared to control without any treatment, and doxorubicin only from day 7 to 18. On qRT-PCR, levels of delivered miRNAs were significantly (P<0.05) higher in groups 1-3 upon UGMMTD treatment compared to controls. TUNEL assay showed that upon UGMMTD, significantly higher levels of apoptotic cell populations were observed in groups 1-3 compared to controls. Toxicity was not observed in various organs of different groups. Conclusions: UGMMTD of miRNA-100/miRNA-122/antimiRNA-10b/antimiRNA-21 combination improved therapeutic outcome of doxorubicin chemotherapy in mouse models of HCC by substantial inhibition of tumor growth and significant increase in apoptotic index.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Ramasamy Paulmurugan
- Department of Radiology, Stanford University, School of Medicine, Stanford, California, USA
| |
Collapse
|
|
47
|
Mir IH, Jyothi KC, Thirunavukkarasu C. The prominence of potential biomarkers in the diagnosis and management of hepatocellular carcinoma: Current scenario and future anticipation. J Cell Biochem 2021; 123:1607-1623. [PMID: 34897788 DOI: 10.1002/jcb.30190] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/13/2021] [Accepted: 11/17/2021] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive and truculent types of cancer. Early detection of HCC is a massive concern that can boost the overall survival rates of HCC patients. As a result, there is a continual quest for advancements in screening, diagnosis, and treatment strategies to enhance the prognosis at its early stages. However, the confluence of inflammation and cirrhosis hampers the early detection of HCC. The analysis of different types of biomarkers such as tissue biomarkers, serum biomarkers, protein biomarkers, autoantibody markers, and improved imaging techniques has played a vital role in ameliorating HCC monitoring responses. Therefore biomarkers that can identify HCC early with a high degree of sensitivity and specificity might be prodigiously serviceable in the diagnosis and treatment of this notorious disorder. This study offers an overview of the contemporary understanding of several types of biomarkers implicated in hepatocarcinogenesis and their applications in monitoring, diagnosis, and prognosis presage. In additament, we address the role of image techniques associated with HCC diagnosis.
Collapse
Affiliation(s)
- Ishfaq Hassan Mir
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
| | - K C Jyothi
- Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, India
| | | |
Collapse
|
|
48
|
Nimitrungtawee N, Inmutto N, Chattipakorn SC, Chattipakorn N. Extracellular vesicles as a new hope for diagnosis and therapeutic intervention for hepatocellular carcinoma. Cancer Med 2021; 10:8253-8271. [PMID: 34708589 PMCID: PMC8633266 DOI: 10.1002/cam4.4370] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/09/2021] [Accepted: 10/07/2021] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer with a high mortality rate. Early diagnosis and treatment before tumor progression into an advanced stage is ideal. The current diagnosis of HCC is mainly based on imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging. These methods have some limitations including diagnosis in the case of very small tumors with atypical imaging patterns. Extracellular vesicles (EVs) are nanosized vesicles which have been shown to act as an important vector for cell-to-cell communication. In the past decade, EVs have been investigated with regard to their roles in HCC formation. Since these EVs contain biomolecular cargo such as nucleic acid, lipids, and proteins, it has been proposed that they could be a potential source of tumor biomarkers and a vector for therapeutic cargo. In this review, reports on the roles of HCC-derived EVs in tumorigenesis, and clinical investigations using circulating EVs as a biomarker for HCC and their potential diagnostic roles have been comprehensively summarized and discussed. In addition, findings from in vitro and in vivo reports investigating the potential roles of EVs as therapeutic interventions are also presented. These findings regarding the potential benefits of EVs will encourage further investigations and may allow us to devise novel strategies using EVs in the early diagnosis as well as for treatment of HCC in the future.
Collapse
Affiliation(s)
- Natthaphong Nimitrungtawee
- Diagnostic Radiology UnitDepartment of RadiologyFaculty of MedicineChiang Mai UniversityChiang MaiThailand
| | - Nakarin Inmutto
- Diagnostic Radiology UnitDepartment of RadiologyFaculty of MedicineChiang Mai UniversityChiang MaiThailand
| | - Siriporn C. Chattipakorn
- Cardiac Electrophysiology Research and Training CenterFaculty of MedicineChiang Mai UniversityChiang MaiThailand
- Cardiac Electrophysiology UnitDepartment of PhysiologyFaculty of MedicineChiang Mai UniversityChiang MaiThailand
- Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai UniversityChiang MaiThailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training CenterFaculty of MedicineChiang Mai UniversityChiang MaiThailand
- Cardiac Electrophysiology UnitDepartment of PhysiologyFaculty of MedicineChiang Mai UniversityChiang MaiThailand
- Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai UniversityChiang MaiThailand
| |
Collapse
|
|
49
|
Circulating MicroRNA-21 As A Novel Noninvasive Biomarker for Hepatocellular Carcinoma Compared with Alpha Fetoprotein Gold Test. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2021. [DOI: 10.22207/jpam.15.4.75] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the greatest traditional kind of pre-eminent cancer worldwide, which happens mainly in chronic liver disease and cirrhotic patients. The available surveillance strategies for suspected HCC patients include serum alpha-fetoprotein (AFP) and liver imaging have been mainly recommended. However, the sensitivity and selectivity of these diagnostic strategies especially in the early stages of HCC have many obstacles. MicroRNAs (miRNAs) are non-coding RNAs that are 18–25 nucleotides in length. Plasma miRNAs may be a promising new biomarker for cancer detection and prognosis in the early stages. Assessment of Plasma MicroRNA-21 (miRNA-21) significance as a noninvasive Hepatocellular carcinoma marker compared with AFP gold standard test to improve HCC early diagnostic power. This is a prospective research project that included 90 patients in total, split into three classes., liver cirrhosis patients (LC) without any malignancies and (HCC) patients in addition to the healthy control group. Patients and controls were subjected to the clinical studies, routine investigations, imaging studies, and detection of plasma miRNA-21 & AFP. miRNA-21 showed a highly significant difference in the 3 studied groups. Control group with LC group, control group with HCC group, and LC group with HCC group P value (P 0.0001, P1 0.0001, P2 0.0001and P3 0.0001) respectively. Also, a highly significant difference was observed between pre-TACE and post-TACE miRNA-21 in the HCC group P value (0.0001). Circulating miRNA-21 may be used as a noninvasive co biomarker with AFP to increase HCC diagnostic accuracy in its early stages.
Collapse
|
|
50
|
Han Z, Li K, Wu J, Wang K, Qiu C, Ye H, Cui C, Song C, Wang K, Shi J, Wang P, Zhang J. Diagnostic value of RNA for hepatocellular carcinoma: a network meta-analysis. Biomark Med 2021; 15:1755-1767. [PMID: 34783583 DOI: 10.2217/bmm-2021-0327] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.
Collapse
Affiliation(s)
- Zhuo Han
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Keming Li
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Jinyu Wu
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Keyan Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China.,Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| | - Cuipeng Qiu
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Hua Ye
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Chi Cui
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China.,Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| | - Chunhua Song
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Kaijuan Wang
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Jianxiang Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China.,Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China
| | - Jianying Zhang
- College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.,Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China.,Henan Institute of Medical & Pharmaceutical Sciences, Zhengzhou University, 40 Daxue Road, Zhengzhou, 450052, China
| |
Collapse
|