scholarly journals Liquid Biopsy for Colorectal Adenoma: Is the Exosomal miRNA Derived from Organoid a Potential Diagnostic Biomarker?

2020 ◽  
Author(s):  
Tomoyuki Handa ◽  
Masatake Kuroha ◽  
Hiroshi Nagai ◽  
Yusuke Shimoyama ◽  
Takeo Naito ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Colorectal Adenoma ◽  
Liquid Biopsy ◽  
Expression Profiles ◽  
Human Colon ◽  
Normal Colon ◽  
Organoid Culture ◽  
Large Size ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Abstract Background: MicroRNAs (miRNAs) have attracted considerable attention as tumor biomarkers. Nevertheless, few reports have described studies of colorectal adenoma (CRA) for liquid biopsy. Recently, organoid culture system development has supported the long-term expansion of investigations of human colon epithelium. This study examined the profile of exosomal miRNAs extracted from CRA organoid and potentiation of candidate miRNAs for clinical application of liquid biopsy in CRA patients. Method: We established organoids from normal colon tissues and CRA from endoscopically resected specimens. Exosomes were prepared from the conditioned medium of the organoids. miRNAs were prepared from the exosomes and their source organoids. The microRNA expression profiles were compared using microarray analysis. To investigate exosomal miRNAs extracted from organoid culture as a candidate for liquid biopsy, we prospectively compared changes in the expression of serum and exosomal miRNA before and after endoscopic resection in 26 patients with CRA.Result: We established three organoid lines from normal colon epithelium and CRA. Microarray analysis revealed that seven exosomal miRNAs expression in CRA organoids were increased compared with normal colon organoids: miR-4323, miR-4284, miR-1268a, miR-1290, miR-6766-3p, miR-21-5p, and miR-1246. The expressions of four exosomal miRNAs (miR-4323, miR-4284, miR-1290, and miR-1246) and two serum miRNAs (miR-1290 and miR-1246) were significantly lower in post-treatment sera. Combinations of four exosomal miRNA expressions can differentiate both CRA and large-size (>12.6 cm2) CRA with respective areas under the curve (AUCs) of 0.698 (95% CI = 0.536–0.823) and 0.834 (95% CI = 0.660–0.929). Combinations of two-serum miRNA expression can differentiate both CRA and large-size CRA with respective AUCs of 0.691 (95% CI = 0.528–0.817) and 0.834 (95% CI = 0.628–0.938). Conclusion: This report is the first to show that exosomal miRNAs derived from CRA organoid culture have potential for use as diagnostic biomarkers for CRA.

scholarly journals Role of Exosomal miRNA in Bladder Cancer: A Promising Liquid Biopsy Biomarker

2021 ◽  
Vol 22 (4) ◽  
pp. 1713
Author(s):  
Xuan-Mei Piao ◽  
Eun-Jong Cha ◽  
Seok Joong Yun ◽  
Wun-Jae Kim
Keyword(s):  
Cancer Research ◽  
Bladder Cancer ◽  
Liquid Biopsy ◽  
Tumor Development ◽  
Great Promise ◽  
Comprehensive Information ◽  
Exosomal Mirnas ◽  
Genetic Landscape ◽  
Exosomal Mirna

Bladder cancer (BCa) is the most prevalent neoplasia of the urinary tract. Unfortunately, limited improvements in effective BCa management have meant that it remains a challenging disease. Cystoscopy has been the gold standard for BCa diagnosis and surveillance for over two centuries but is an invasive and expensive approach. Recently, liquid biopsy has been identified as a promising field of cancer research, due to its noninvasiveness and ease of sampling. Liquid biopsy samples could provide comprehensive information regarding the genetic landscape of cancer and could track genomic evolution of the disease over time. Exosomes, which contain RNAs, DNAs, and proteins, are a potential source of tumor biomarkers in liquid biopsy samples. In particular, exosomal miRNAs (exomiRs) hold great promise as biomarkers for tumor development and progression. In this review, we provide an overview of liquid biopsy biomarkers, with a particular focus on the use of exomiRs as biomarkers of cancer, and summarize their clinical implications for BCa. Finally, we discuss the future perspectives of these biomarkers in cancer research.

scholarly journals The accumulation of exosome-associated microRNA-1246 and microRNA-150-3p in human red blood cell suspensions

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yujie Kong ◽  
Xue Tian ◽  
Rui He ◽  
Chenyue Li ◽  
Haixia Xu ◽  
...  
Keyword(s):  
Blood Cell ◽  
Signaling Pathways ◽  
Red Blood Cell ◽  
Expression Profiles ◽  
Storage Period ◽  
Gene Chip ◽  
Ras Signaling ◽  
Qrt Pcr ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Abstract Background Transfusion-related immunomodulation (TRIM) can be caused by exosomes, in which case, microRNAs (miRNAs) are one critical factor impacting exosome behavior. This study aims to investigate and analyze the expression profiles of exosomal miRNA in red blood cell (RBC) suspensions during storage and to identify potential TRIM-related miRNAs as well as their potential functions. Methods A total of 25 packs of RBC suspensions were randomly collected. Exosome were extracted by ultracentrifugation and then identified and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and western blot (WB). Exosomal miRNA profiles were acquired using gene chips in five packs on week 1 and week 5. The expression data were compared from the two time points identifying accumulated miRNAs with statistical significance and their predicted targeting genes were analyzed. Based on the gene chip results, quantitative reverse transcription-polymerase chain reactions (qRT-PCR) were performed to verify miRNA accumulation in the rest 20 packs sampling on week 1, 3 and 5. Results Gene chip analysis revealed that most exosomal miRNAs were enriched as the storage period progressed. Compared to samples from week 1, week 5 samples exhibited a total of 539 differential miRNA expressions, among which, 159 were statistically significant (P < 0.05) and 148 (93.08%) were accumulated. In the bioinformatics functional analysis, significant immunoregulatory annotations related to the thyroid hormone, mitogen-activated protein kinase (MAPK), focal adhesion and RAS signaling pathways were identified. The top 17 differential expression miRNAs were validated by qRT-PCR. The results confirmed that all the 17 miRNAs were accumulated with increasing storage time. In particular, miRNA-1246 and miRNA-150-3p were the most enriched strands by more than 150-folds in the 5-week storage period. Conclusions As storage progressed, numerous exosomal miRNAs accumulated in the RBC suspensions, which are informatically connected to multiple immuno-signaling pathways. MiRNA-1246 and miRNA-150-3p may be essential mediators impacting the immunoregulation functions of exosomes in RBC suspensions, considering their significant accumulating scales. Further research should therefore focus on the relationship between these miRNAs and TRIM.

scholarly journals Promoting Osteogenic Differentiation of Human Adipose-Derived Stem Cells by Altering the Expression of Exosomal miRNA

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Shude Yang ◽  
Shu Guo ◽  
Shuang Tong ◽  
Xu Sun
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Expression Profiles ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Adipose Derived Stem Cells ◽  
Exosomal Mirnas ◽  
Regulatory Functions ◽  
Exosomal Mirna

Human adipose-derived stem cells (ADSCs) can release exosomes; however, their specific functions remain elusive. In this study, we verified that exosomes derived from osteogenically differentiated ADSCs can promote osteogenic differentiation of ADSCs. Furthermore, in order to investigate the importance of exosomal microRNAs (miRNAs) in osteogenic differentiation of ADSCs, we used microarray assays to analyze the expression profiles of exosomal miRNAs derived from undifferentiated as well as osteogenically differentiated ADSCs; 201 miRNAs were upregulated and 33 miRNAs were downregulated between the two types of exosomes. Additionally, bioinformatic analyses, which included gene ontology analyses, pathway analysis, and miRNA-mRNA-network investigations, were performed. The results of these analyses revealed that the differentially expressed exosomal miRNAs participate in multiple biological processes, such as gene expression, synthesis of biomolecules, cell development, differentiation, and signal transduction, among others. Moreover, we found that these differentially expressed exosomal miRNAs connect osteogenic differentiation to processes such as axon guidance, MAPK signaling, and Wnt signaling. To the best of our knowledge, this is the first study to identify and characterize exosomal miRNAs derived from osteogenically differentiated ADSCs. This study confirms that alterations in the expression of exosomal miRNAs can promote osteogenic differentiation of ADSCs, which also provides the foundation for further research on the regulatory functions of exosomal miRNAs in the context of ADSC osteogenesis.

scholarly journals Human Periodontal Ligament Stem Cell-Derived Exosomes Promote Bone Regeneration by Altering MicroRNA Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Ting Liu ◽  
Wenyun Hu ◽  
Xue Zou ◽  
Jingchen Xu ◽  
Shushu He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Expression Profiles ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Regulatory Function ◽  
Exosomal Mirnas ◽  
Osteogenic Induction ◽  
Exosomal Mirna

The role and underlying mechanism of exosomes derived from human periodontal ligament stem cells (PDLSC) in osteogenesis are unclear. In the present study, we identified the exosomes derived from PDLSCs and found that osteogenic induction can enhance the osteogenic ability of PDLSC-derived exosomes in promoting the osteogenic differentiation of rat bone marrow stem cells (BMSCs). To investigate the underlying mechanism, we analyzed the exosomal miRNA expression profiles of undifferentiated and osteogenic differentiated PDLSCs by RNA sequencing. The results showed that seventy-two miRNAs were upregulated and thirty-five miRNAs were downregulated after osteogenic induction. The results of Gene Ontology analysis and pathway analysis demonstrated that the target genes of differentially expressed exosomal miRNAs participate in the regulation of a variety of biological processes, such as catalytic activity, protein binding, metabolic processes, cell development, and differentiation, and are enriched in osteogenic differentiation-related pathways, such as MAPK signaling, AMPK signaling, and insulin signaling pathways. Our results reveal for the first time that the exosomal miRNAs derived from osteogenic differentiated PDLSCs may promote the osteogenic differentiation of BMSCs, which provides a basis for further research on the regulatory function of exosomal miRNA of PDLSCs during osteogenesis.

scholarly journals Liquid Biopsy for Colorectal Adenoma: Is the Exosomal miRNA Derived From Organoid a Potential Diagnostic Biomarker?

2021 ◽  
Vol 12 (5) ◽  
pp. e00356
Author(s):  
Tomoyuki Handa ◽  
Masatake Kuroha ◽  
Hiroshi Nagai ◽  
Yusuke Shimoyama ◽  
Takeo Naito ◽  
...  
Keyword(s):  
Colorectal Adenoma ◽  
Liquid Biopsy ◽  
Diagnostic Biomarker ◽  
Exosomal Mirna

scholarly journals Regulation of Serum Exosomal MicroRNAs in Mice Infected with Orientia tsutsugamushi

2020 ◽  
Vol 9 (1) ◽  
pp. 80
Author(s):  
Le Jiang ◽  
Tatyana Belinskaya ◽  
Zhiwen Zhang ◽  
Teik-Chye Chan ◽  
Wei-Mei Ching ◽  
...  
Keyword(s):  
Post Infection ◽  
Viral Infections ◽  
Scrub Typhus ◽  
Late Phase ◽  
Many Body ◽  
Host Immune Responses ◽  
Lethal Infection ◽  
Exosomal Mirnas ◽  
Exosomal Mirna ◽  
Intercellular Communications

Exosomes are small extracellular vesicles that carry proteins, lipids, and nucleic acids. They are circulated in many body fluids and play an important role in intercellular communications. MicroRNAs (miRNAs), as major components of exosomes, are often regulated in many diseases including bacterial and viral infections. Functionally, exosome-carried miRNAs interact with various immune cells and affect their behavior. Little is known whether exosomal miRNAs are regulated during scrub typhus, a potentially lethal infection caused by intracellular bacteria, Orientiatsutsugamushi. In the present study, we utilized a scrub typhus mouse model and collected serum at various time points post infection. A custom quantitative PCR array covering 92 murine miRNAs was used to profile serum exosomal miRNAs. A total of 12 miRNAs were found to be significantly up- or down-regulated at least at one time point post infection when compared to uninfected animals. Further analysis identified multiple miRNAs in the let-7 family that were consistently down-regulated at early and late phase of infection. Functionally, serum exosomes isolated from infected mice displayed strong proinflammatory effect when incubated with bone marrow-derived macrophages. Our data revealed dynamic regulations of serum exosomal miRNA during scrub typhus infection, which could significantly influence host immune responses and disease outcome.

scholarly journals Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2110
Author(s):  
Oyeon Cho ◽  
Do-Wan Kim ◽  
Jae-Youn Cheong
Keyword(s):  
Cervical Cancer ◽  
Pilot Study ◽  
Biological Functions ◽  
Patients With Cancer ◽  
Initial Stage ◽  
Exosomal Mirnas ◽  
Early Progression ◽  
Before And After ◽  
Microenvironmental Factors ◽  
Exosomal Mirna

Plasma exosomal miRNAs are key regulators of cell-cell interactions associated with several biological functions in patients with cancer. This pilot study aimed to investigate the log2 fold change (log2FC) of the expression of exosomal miRNAs and related mRNAs in the blood of patients with cervical cancer to identify prognostic markers better than those currently available. We sequenced plasma exosomal RNA from 56 blood samples collected from 28 patients with cervical cancer, who had been treated with concurrent chemoradiotherapy (CCRT). Changes in the expression of miRNAs and mRNAs before and after CCRT were represented as log2FC. Their biological functions were studied by miRNA-mRNA network analysis, using ingenuity pathway analysis, after the selection of two groups of miRNAs, each associated with early progression (EP) and metastasis, also described as initial stage. Seven patients experienced EP, three of whom died within four months after progression. Reduced levels of miR-1228-5p, miR-33a-5p, miR-3200-3p, and miR-6815-5p and increased levels of miR-146a-3p in patients with EP revealed unresolved inflammation, with accompanying increased expression of PCK1 and decreased expression of FCGR1A. Increased levels of miR-605-5p, miR-6791-5p, miR-6780a-5p, and miR-6826-5p and decreased levels of miR-16-1-3p (or 15a-3p) were associated with the degree of metastasis and led to the systemic activation of myeloid, endothelial, and epithelial cells, as well as neurons, phagocytes, and platelets. Log2FCs in the expression of miRNAs and mRNAs from plasma exosomes after CCRT are associated with EP and metastasis, reflecting unresolved inflammation and systemic microenvironmental factors, respectively. However, this study, supported by preliminary data insufficient to reach clear conclusions, should be verified in larger prospective cohorts.

scholarly journals Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Zhou ◽  
Jianghua Ming ◽  
Yaming Li ◽  
Bochun Li ◽  
Ming Deng ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Apoptotic Cell ◽  
Synovial Fibroblasts ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Exosomal Mirnas ◽  
Exosomal Mirna ◽  
And Control ◽  
And Cartilage

AbstractMicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

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