Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1125 2022-11-09 10:29:09 |
2 Format correction Meta information modification 1125 2022-11-10 01:52:40 | |
3 Changed the symbol + 2 word(s) 1127 2022-11-11 15:39:55 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Lin, B.;  Jiang, J.;  Jia, J.;  Zhou, X. Exosomal miRNA Biosensing for Liquid Biospy. Encyclopedia. Available online: https://encyclopedia.pub/entry/33750 (accessed on 19 June 2024).
Lin B,  Jiang J,  Jia J,  Zhou X. Exosomal miRNA Biosensing for Liquid Biospy. Encyclopedia. Available at: https://encyclopedia.pub/entry/33750. Accessed June 19, 2024.
Lin, Bingqian, Jinting Jiang, Jingxuan Jia, Xiang Zhou. "Exosomal miRNA Biosensing for Liquid Biospy" Encyclopedia, https://encyclopedia.pub/entry/33750 (accessed June 19, 2024).
Lin, B.,  Jiang, J.,  Jia, J., & Zhou, X. (2022, November 09). Exosomal miRNA Biosensing for Liquid Biospy. In Encyclopedia. https://encyclopedia.pub/entry/33750
Lin, Bingqian, et al. "Exosomal miRNA Biosensing for Liquid Biospy." Encyclopedia. Web. 09 November, 2022.
Exosomal miRNA Biosensing for Liquid Biospy
Edit

As a noninvasive detection technique, liquid biopsy plays a valuable role in cancer diagnosis, disease monitoring, and prognostic assessment. In liquid biopsies, exosomes are considered among the potential biomarkers because they are important bioinformation carriers for intercellular communication. Exosomes transport miRNAs and, thus, play an important role in the regulation of cell growth and function; therefore, detection of cancer cell-derived exosomal miRNAs (exo-miRNAs) gives effective information in liquid biopsy. 

exosomal miRNA biosensing liquid biopsy

1. Introduction

Cancer is one of the major diseases that threaten human health today, and its incidence and mortality rates are on a continuous rise [1]. Clinical research and practices have shown that the development of precision diagnosis and treatment technologies to achieve early diagnosis and early treatment of tumors is an important strategy to reduce the mortality rate and improve the survival rate of cancer patients [2]. As the gold standard technology for tumor diagnosis, tissue biopsy can obtain pathological information of tumors, including molecular biological characteristics, which provides important reference values for tumor diagnosis, as well as treatment [3]. However, traditional tissue biopsy techniques require invasive sampling procedures or even surgical assistance, and they have limitations such as large sampling bias, difficulty in sampling due to deteriorating clinical conditions or deep tumor location, and sampling lag [4]. Therefore, it is of great significance to explore noninvasive strategies for accurate early tumor diagnosis and monitor. Unlike noninvasive imaging for cancer monitoring [5][6], liquid biopsy is a technique that detects, analyzes, and monitors tumors by analyzing various body fluid samples such as blood or urine [7]. Compared with traditional tissue biopsy techniques that are limited to tumor progression at a single timepoint and suffer from bias due to tumor heterogeneity, liquid biopsy is one of the frontier hotspots in tumor diagnosis because it is less invasive, is convenient for multiple sampling, and can monitor tumor progression in real time.
At present, the main targets of liquid biopsy include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles, such as exosomes [8]. Among these, exosomes derived from cancer cells may serve as a promising biomarker for several cancers [9]. Exosomes, a type of extracellular vesicle (EV), 40-160 nm in size, are secreted by all eukaryotic cells [10]. They have stable structures consisting of bilateral phospholipid membranes with proteins, DNA, mRNAs, microRNAs (miRNAs), etc. inside. These cargoes are proven to play a vital role in cell-to-cell communication [11]. Special markers associated with tumor-derived exosomes may be enriched, which may be useful for diagnosis. In particular, unique nucleic acids contained in exosomes are potentially reliable biomarkers in the diagnosis and progress monitoring of cancer. MicroRNAs are a major class of single-stranded, noncoding RNA with a length of 19-25 nucleotides (nts), which are essential regulators of gene expression, especially in cancer [12]. Recent studies have identified miRNAs in exosomes as potential biomarkers for liquid biopsy and are expected to be used in future clinical tests.

2. The Potential of Exo-miRNAs as Biomarkers in Liquid Biopsy

2.1. MicroRNAs as a Biomarker

Growing evidence has shown that miRNAs play an important role in the process of cancer development, including tumorigenesis, metastasis, and treatment resistance [13]. In most cases, miRNAs bind to their complementary sequences in the 3′ untranslated region (UTR) of target mRNAs to modulate their target [12]. In addition to the predominant mechanism, other non-canonical mechanisms have been demonstrated. Massive research has revealed that miRNAs are greatly involved in human health by regulating more than 60% of protein-coding genes and account for about 1% of the genome [14]. Additionally, the altered expression levels of miRNAs are associated with chromosomal abnormalities in their parent cells. Since then, a large number of studies have made efforts to investigate the noncoding transcriptomes from various cancer types, trying to provide appropriate miRNA candidates as a biomarker in liquid biopsy [15]. Comprehensive studies of the dysregulated profile of miRNAs in circulating environments such as blood have shown that they are associated with cancer [16]. Thus, altered levels of relevant miRNAs in liquid biopsy may provide rich information in cancer diagnosis.

2.2. Exo-miRNAs as Biomarker in Liquid Biopsy

In general, the release of miRNAs circulating in the body fluids follows two paths. The passive path mainly relies on tissue damage, apoptosis, and necrotic cell death. On the other hand, cells can actively encapsulate miRNAs in extracellular vesicles, such as exosomes and ectosomes. It has been shown that about 10% of secretory miRNAs are enriched in exosomes, while the remaining are associated with proteins in the circulation [17][18]. Taking advantage of the membrane structure, the miRNAs show improved stability against the degradation of RNases. Moreover, the intact structure of exosomes is not affected by non-physiological conditions, such as repeated freezing and thawing, extreme pH, or long-term storage, thus allowing the internal miRNAs to remain stable, laying the foundation for the sensitivity of miRNA detection [19].
Recent studies have demonstrated that exosomes derived from cancer cells are ideal candidate biomarkers for early cancer diagnosis and therapeutic monitoring. It has been reported that miRNAs are involved in the pathogenesis of various diseases, including cancer, through the exosomes that are taken up by the recipient cells as cargo [20][21]. Increasing evidence has revealed that miRNAs transferred by exosomes contain valuable information about the original cell types, the recipient cells, and disease progression. It has been reported that the exo-miRNAs derived from cancer cells can promote cell proliferation, migration, and angiogenesis [19], such as exosomal-miR-21 (exo-miR-21) [22], exo-miR-23a [23], exo-miR-100 [24], and so on [25][26]. For instance, exo-miR-21 was investigated as a promising biomarker for breast cancer [27] and ovarian cancer [28]. So far, 2838 miRNAs have been reported to be encapsulated in exosomes from several kinds of cell types (Exocarta) [29]. Therefore, it is of great significance to use exo-miRNAs as a detection target in liquid biopsy for early diagnosis, progression monitoring, and therapy evaluation of cancer.
Several methods for exo-miRNAs analysis have been reported. The common methods used to quantitative and profile miRNAs are quantitative reverse transcription real-time PCR (qRT-PCR) [22], digital PCR [30], and next-generation sequencing (NGS) [31]. However, despite the superior performance of these methods, they have some shortcomings in the application of liquid biopsy. Quantitative real-time PCR (qRT-PCR) has been recognized as the gold standard for miRNA analysis due to its excellent sensitivity and flexibility. However, this method has some problems such as non-absolute quantification, false positives, reliance on expensive equipment, and a large number of biological samples, which limit its application in routine clinical practice [30]. In addition, the ddPCR and NGS usually need high costs and tedious operations, limiting the use of these assays in a large number of clinical liquid biopsy scenarios [32]. Many biosensors are designed to explore disease-associated markers, such as detecting cancer-associated markers for cancer diagnosis [33][34][35]. Compared with the above methods, miRNA detection using biosensors does not require complex steps with shortened detection time and does not require large and expensive instruments, meeting the requirements of rapid and high sensitivity for clinical detection in liquid biopsy.

References

  1. Satish Gopal; Norman E. Sharpless; Cancer as a Global Health Priority. JAMA 2021, 326, 809-810, 10.1001/jama.2021.12778.
  2. David Weller; Peter Vedsted; G. Rubin; Fiona Walter; Jon Emery; Suzanne Scott; Christine E Campbell; Rikke Sand Andersen; William Hamilton; Frede Olesen; et al.Peter W RoseS. NafeesE Van RijswijkS HiomChristiane MuthMartin BeyerRichard D Neal The Aarhus statement: improving design and reporting of studies on early cancer diagnosis. British Journal of Cancer 2012, 106, 1262-1267, 10.1038/bjc.2012.68.
  3. Aristidis Diamantis; Emmanouil Magiorkinis; Helen Koutselini; Fine-needle aspiration (FNA) biopsy: historical aspects. Folia histochemica et cytobiologica 2009, 47, 191-197, 10.2478/v10042-009-0027-x.
  4. Charles Swanton; Intratumor Heterogeneity: Evolution through Space and Time. Cancer Research 2012, 72, 4875-4882, 10.1158/0008-5472.can-12-2217.
  5. Weicai Huang; Yuming Jiang; Wenjun Xiong; Zepang Sun; ChuanLi Chen; Qingyu Yuan; Kangneng Zhou; Zhen Han; Hao Feng; Hao Chen; et al.Xiaokun LiangShitong YuYanfeng HuJiang YuYan ChenLiying ZhaoHao LiuZhiwei ZhouWei WangYikai XuGuoxin Li Noninvasive imaging of the tumor immune microenvironment correlates with response to immunotherapy in gastric cancer. Nature Communications 2022, 13, 5095, 10.1038/s41467-022-32816-w.
  6. Dario Gosmann; Lisa Russelli; Wolfgang A. Weber; Markus Schwaiger; Angela M. Krackhardt; Calogero D’Alessandria; Promise and challenges of clinical non-invasive T-cell tracking in the era of cancer immunotherapy. EJNMMI Research 2022, 12, 5, 10.1186/s13550-022-00877-z.
  7. Emily Crowley; Federica Di Nicolantonio; Fotios Loupakis; Alberto Bardelli; Liquid biopsy: monitoring cancer-genetics in the blood. Nature Reviews Clinical Oncology 2013, 10, 472-484, 10.1038/nrclinonc.2013.110.
  8. Ramanathan Vaidyanathan; Ren Hao Soon; Pan Zhang; Kuan Jiang; Chwee Teck Lim; Cancer Diagnosis: From Tumor to Liquid Biopsy and Beyond. Lab on a Chip 2019, 19, 11-34, 10.1039/c8lc00684a.
  9. Raghu Kalluri; The biology and function of exosomes in cancer. JCI Insight 2016, 126, 1208-1215, 10.1172/jci81135.
  10. Raghu Kalluri; Valerie S. LeBleu; The biology , function , and biomedical applications of exosomes. Science 2020, 367, eaau6977, 10.1126/science.aau6977.
  11. Joana Maia; Sergio Caja; Maria Carolina Strano Moraes; Nuno Couto; Bruno Costa-Silva; Exosome-Based Cell-Cell Communication in the Tumor Microenvironment. Frontiers in Cell and Developmental Biology 2018, 6, 18, 10.3389/fcell.2018.00018.
  12. Shuibin Lin; Richard I. Gregory; MicroRNA biogenesis pathways in cancer. Nature Reviews Cancer 2015, 15, 321-333, 10.1038/nrc3932.
  13. Gianpiero Di Leva; Carlo M Croce; miRNA profiling of cancer. Current opinion in genetics & development 2013, 23, 3-11, 10.1016/j.gde.2013.01.004.
  14. Robin C. Friedman; Kyle Kai-How Farh; Christopher B. Burge; David P. Bartel; Most mammalian mRNAs are conserved targets of microRNAs. Genome Research 2009, 19, 92-105, 10.1101/gr.082701.108.
  15. Jin Wang; Jinyun Chen; Subrata Sen; MicroRNA as Biomarkers and Diagnostics. Journal of Cellular Physiology 2016, 231, 25-30, 10.1002/jcp.25056.
  16. Kazuharu Kai; Rachel L. Dittmar; Subrata Sen; Secretory microRNAs as biomarkers of cancer. Seminars in cell & developmental biology 2018, 78, 22-36, 10.1016/j.semcdb.2017.12.011.
  17. Kasey C. Vickers; Brian T. Palmisano; Bassem M. Shoucri; Robert D. Shamburek; Alan T. Remaley; MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nature cell biology 2011, 13, 423-433, 10.1038/ncb2210.
  18. Jason D. Arroyo; John R. Chevillet; Evan M. Kroh; Ingrid K. Ruf; Colin C. Pritchard; Donald F. Gibson; Patrick S. Mitchell; Christopher F. Bennett; Era L. Pogosova-Agadjanyan; Derek L. Stirewalt; et al.Jonathan F. TaitMuneesh Tewari Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proceedings of the National Academy of Sciences of the United States of America 2011, 108, 5003-5008, 10.1073/pnas.1019055108.
  19. Arron Thind; Clive Wilson; Exosomal miRNAs as cancer biomarkers and therapeutic targets. Journal of Extracellular Vesicles 2016, 5, 31292, 10.3402/jev.v5.31292.
  20. Tae Matsumura; K Sugimachi; H Iinuma; Yoko Takahashi; Junji Kurashige; Genta Sawada; Mitsuharu Ueda; Ryutaro Uchi; Hiroaki Ueo; Yasuo Takano; et al.Yoshiaki ShindenH EguchiHiroshi YamamotoYuichiro DokiMasaki MoriTakahiro OchiyaKenichi Mimori Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. British Journal of Cancer 2015, 113, 275-281, 10.1038/bjc.2015.201.
  21. Hao Wang; Ran Peng; Junjie Wang; Zelian Qin; Lixiang Xue; Circulating microRNAs as potential cancer biomarkers: the advantage and disadvantage. Clinical Epigenetics 2018, 10, 59, 10.1186/s13148-018-0492-1.
  22. Yuan Zhou; Haozhen Ren; Bo Dai; Jun Li; Longcheng Shang; Jianfei Huang; Xiaolei Shi; Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts. Journal of Experimental & Clinical Cancer Research 2018, 37, 324, 10.1186/s13046-018-0965-2.
  23. Y-L Hsu; J-Y Hung; W-A Chang; Y-S Lin; Y-C Pan; P-H Tsai; C-Y Wu; P-L Kuo; Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1. Oncogene 2017, 36, 4929-4942, 10.1038/onc.2017.105.
  24. Katayoon Pakravan; Sadegh Babashah; Majid Sadeghizadeh; Seyed Javad Mowla; Majid Mossahebi-Mohammadi; Farangis Ataei; Nasim Dana; Mohammad Javan; MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells. Cellular Oncology 2017, 40, 457-470, 10.1007/s13402-017-0335-7.
  25. Divya Bhagirath; Thao Ly Yang; Nathan Bucay; Kirandeep Sekhon; Shahana Majid; Varahram Shahryari; Rajvir Dahiya; Yuichiro Tanaka; Sharanjot Saini; microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer. Cancer Research 2018, 78, 1833-1844, 10.1158/0008-5472.can-17-2069.
  26. Ramesh Singh; Radhika Pochampally; Kounosuke Watabe; Zhaohui Lu; Yin-Yuan Mo; Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer. Molecular Cancer 2014, 13, 256, 10.1186/1476-4598-13-256.
  27. Li Liu; Hao Lu; Ruixue Shi; Xin-Xin Peng; Qingwei Xiang; Bowen Wang; Qiang-Qiang Wan; Yujie Sun; Fan Yang; Guo-Jun Zhang; et al. Synergy of Peptide-Nucleic Acid and Spherical Nucleic Acid Enabled Quantitative and Specific Detection of Tumor Exosomal MicroRNA. Analytical Chemistry 2019, 91, 13198-13205, 10.1021/acs.analchem.9b03622.
  28. Chia-Yu Sung; Chi-Chien Huang; Yi-Sin Chen; Keng-Fu Hsu; Gwo-Bin Lee; Isolation and quantification of extracellular vesicle-encapsulated microRNA on an integrated microfluidic platform. Lab on a Chip 2021, 21, 4660-4671, 10.1039/d1lc00663k.
  29. Shivakumar Keerthikumar; David Chisanga; Dinuka Ariyaratne; Haidar Al Saffar; Sushma Anand; Kening Zhao; Monisha Samuel; Mohashin Pathan; Markandeya Jois; Naveen Chilamkurti; et al.Lahiru GangodaSuresh Mathivanan ExoCarta: A Web-Based Compendium of Exosomal Cargo. Journal of Molecular Biology 2016, 428, 688-692, 10.1016/j.jmb.2015.09.019.
  30. Cong Wang; Qiang Ding; Pamela Plant; Mayada Basheer; Chuance Yang; Eriny Tawedrous; Adriana Krizova; Carl Boulos; Mina Farag; Yufeng Cheng; et al.George M. Yousef Droplet digital PCR improves urinary exosomal miRNA detection compared to real-time PCR. Clinical biochemistry 2019, 67, 54-59, 10.1016/j.clinbiochem.2019.03.008.
  31. Xiance Jin; Yanfan Chen; Hanbin Chen; Shaoran Fei; Didi Chen; Xiaona Cai; Linger Liu; Baochai Lin; Huafang Su; Lihao Zhao; et al.Meng SuHuanle PanLanxiao ShenDeyao XieCongying Xie Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non-Small Cell Lung Cancer Using Next-Generation Sequencing. Clinical Cancer Research 2017, 23, 5311-5319, 10.1158/1078-0432.ccr-17-0577.
  32. Lesley Cheng; Xin Sun; Benjamin J. Scicluna; Bradley M. Coleman; Andrew Hill; Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA in human urine. Kidney International 2014, 86, 433-444, 10.1038/ki.2013.502.
  33. V.S.P.K. Sankara Aditya Jayanthi; Asim Bikas Das; Urmila Saxena; Recent advances in biosensor development for the detection of cancer biomarkers. Biosensors and Bioelectronics 2017, 91, 15-23, 10.1016/j.bios.2016.12.014.
  34. Kurmendra; Rajesh Kumar; MEMS based cantilever biosensors for cancer detection using potential bio-markers present in VOCs: a survey. Microsystem Technologies 2019, 25, 3253-3267, 10.1007/s00542-019-04326-1.
  35. Jagdeep Rahul; Rajesh Kumar; Micro-cantilevered MEMS Biosensor for Detection of Malaria Protozoan Parasites. Journal of Computational Applied Mechanics 2019, 50, 99-107, 10.22059/JCAMECH.2019.276035.362.
More
Information
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , ,
View Times: 362
Revisions: 3 times (View History)
Update Date: 11 Nov 2022
1000/1000
Video Production Service