Exosomal microRNAs isolated from plasma of mesenteric veins linked to liver metastases in resected patients with colon cancer

Monzó, Mariano; Santasusagna, Sandra; Moreno, Isabel; Martínez, Francisco García; Hernández, R; Muñoz, Carmen; Castellano, Joan Josep; Moreno, J.; Navarro, Alfons

doi:10.18632/oncotarget.16103

Cited by 40 publications

(45 citation statements)

References 30 publications

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“…For example, in a study on plasma samples from male rats performed in 2017, the authors identified ten arterial and fourteen venous highly expressed miRNAs, and the miRNA profiles in arterial plasma showed higher correlation with that in tissue [291]. In humans, sample studies showed similar observations, leading to the conclusion that the blood sampling method should be carefully chosen for specific miRNA biomarkers [292,293]. miRNAs can be detected using various specific and sensitive approaches, including Northern blot analysis [294,295], in situ hybridization [296], real-time PCR [95,297], miRNA microarray [298,299] and next-generation sequencing (NGS) [300], and some of them are already used as diagnostic or prognostic markers, this demonstrating their utility in both clinical and personalized medicine.…”

Section: Limitations Of Circulating Mirnas As Biomarkersmentioning

confidence: 98%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

913

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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Section: Limitations Of Circulating Mirnas As Biomarkersmentioning

confidence: 98%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

913

583

View full text Add to dashboard Cite

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“…This suggests that miRNAs detected in PV plasma or serum may not be indicative of those found in the primary tumor [44]. Previous studies by our group found that expression levels of miR-21, a widely known tumor-related miRNA [45], were significantly higher in MV plasma than in PV plasma [36], and levels of miR-15b, miR-155, miR-328, and let-7g were also higher in MV than in PV plasma [37]. Taken together with the results of the present study, these findings indicate that the primary tumor in CC releases high concentrations of these miRNAs that are later diluted in the circulatory system, leading us to suggest that MV plasma is a superior source for the detection of miRNAs.…”

Section: Discussionmentioning

confidence: 84%

“…Exosome Isolation, Characterization, and RNA Isolation Exosome isolation characterization and miRNA analyses were performed from 250 μL of plasma samples by ultracentrifugation as previously described [38,39]. Exosome characterization was done by 2 methods: (1) Cryo transmission electron microscopy (cryo-TEM) in a Jeol JEM 2011 transmission electron microscope at the Microscope Facility of the Autonomous University of Barcelona; and (2) western blot analysis, using the exosome marker TSG101.…”

Section: Quantitative Reverse Transcription Pcr Analysis Of Plasma Mirnamentioning

confidence: 99%

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Prognostic Impact of miR-200 Family Members in Plasma and Exosomes from Tumor-Draining versus Peripheral Veins of Colon Cancer Patients

et al. 2018

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Objective: To evaluate the prognostic potential of expression levels of miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429, miR-141) in plasma and exosomes from the tumor-draining vein (mesenteric vein [MV]) and peripheral vein (PV) of colon cancer (CC) patients. Methods: We analyzed the expression of miR-200 family members in matched samples of MV and PV plasma from 50 resected patients with CC and correlated our findings with overall survival (OS). We also examined the content of these microRNAs in MV and PV exosomes. Results: Expression levels were higher in MV than in PV (miR-200a, p < 0.001; miR-200b, p < 0.001; miR-429, p = 0.01; miR-200c, p = 0.05; miR-141, p = 0.05). Low levels of both miR-200c and miR-141 in MV plasma were associated with longer OS (p = 0.02). This association was maintained for the MV exosome cargo of miR-200c and miR-141 (p = 0.02). Conclusion: Our findings provide the first indication that expression levels of miR-200c and miR-141 in MV plasma can identify CC patients with poor prognosis. In addition, our results lend further support to the premise that tumor-draining veins constitute a better source of biomarkers than do PVs.

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“…They are capable of being transported to local or distant anatomic locations where they can transduce signals or other information [33]. Exosomes have attracted the attention of many investigators and now are being evaluated as a potential biomarker [34]. More information regarding exosomes and their structure and function could be found in a review by Chlebowski and associates [35].…”

Section: Genetic Biomarkersmentioning

confidence: 99%

Some aspects of cancer biomarkers and their clinical application in solid tumors – revisited

Isaac¹,

Elayoubi²,

A³

et al. 2017

J Cancer Res Ther.

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Cancer biomarkers can be used for a variety of purposes related to screening, prediction, stratification, detection, diagnosis, prognosis, treatment design, and monitoring of a therapeutic response. One of the most important characteristics of a given biomarker includes ease of collection allowing for a non-invasive approach and frequent sampling. Such samples may be obtained from serum or plasma, sputum, bronchoalveolar lavage, saliva, nipple discharge, pleural, or peritoneal effusions. Validation of different biomarkers is considered a mandatory method for useful evaluation. In this review, we highlight the clinical applicability of some cancer biomarkers, as well as future approaches for their development and collection, which may help guide clinicians and researchers. The role of liquid biopsies will also be summarized. Further studies using liquid biopsies are needed to elucidate the significance of various sources of biomarkers suitable for clinical application.

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Exosomal microRNAs isolated from plasma of mesenteric veins linked to liver metastases in resected patients with colon cancer

Cited by 40 publications

References 30 publications

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Prognostic Impact of miR-200 Family Members in Plasma and Exosomes from Tumor-Draining versus Peripheral Veins of Colon Cancer Patients

Some aspects of cancer biomarkers and their clinical application in solid tumors – revisited

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