scholarly journals Identification and Characterization of Circulating MicroRNAs as Novel Biomarkers in Dogs With Heart Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Woong-Bin Ro ◽  
Min-Hee Kang ◽  
Doo-Won Song ◽  
Heyong-Seok Kim ◽  
Ga-Won Lee ◽  
...  

Background: Previous studies in humans have confirmed dysregulations of circulating microRNAs (miRNAs) in patients with various cardiovascular diseases. However, studies on circulating miRNAs in dogs with various heart diseases are limited in number. This study aimed to identify significantly dysregulated circulating miRNAs and characterize them as novel biomarkers in dogs with heart diseases.Materials and Methods: Circulating levels of 11 miRNAs were investigated in serum samples of 82 dogs (72 with heart diseases and 10 healthy dogs) using quantitative reverse transcription-polymerase chain reaction. The results were correlated to clinical data including echocardiographic results and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.Results: Upregulation of cfa-miR-130b was observed in dogs with myxomatous mitral valve degeneration (MMVD) stage B, patent ductus arteriosus, and pulmonic stenosis. In dogs with MMVD stage B, cfa-miR-130b was upregulated and correlated with clinical indices. In receiver operating characteristic (ROC) analysis, cfa-miR-130b accurately distinguished dogs with diseases from healthy dogs. We also observed that cfa-miR-375 and cfa-let-7b were upregulated in dogs with concentric cardiac hypertrophy. The cfa-miR-375 was correlated with concentric hypertrophy indices and was an accurate indicator of concentric hypertrophy in ROC analysis.Conclusions: The miRNAs identified in this study may be used as novel biomarkers and possible candidates for therapeutic targets in various canine heart diseases.

2021 ◽  
Vol 8 ◽  
Author(s):  
Woong-Bin Ro ◽  
Min-Hee Kang ◽  
Doo-Won Song ◽  
Sung-Hun Lee ◽  
Hee-Myung Park

This study aimed to identify the expression profile of circulating microRNAs in dogs with eccentric or concentric cardiac hypertrophy. A total of 291 microRNAs in serum samples of five dogs with myxomatous mitral valve degeneration (MMVD) and five dogs with pulmonic stenosis (PS) were compared with those of five healthy dogs using microarray analysis. Results of microarray analysis revealed up-regulation of cfa-miR-130b [fold change (FC) = 2.13, p = 0.014), down-regulation of cfa-miR-375 (FC = 1.51, p = 0.014), cfa-miR-425 (FC = 2.56, p = 0.045), cfa-miR-30d (FC = 3.02, p = 0.047), cfa-miR-151 (FC = 1.89, p = 0.023), cfa-miR-19b (FC = 3.01, p = 0.008), and cfa-let-7g (FC = 2.53, p = 0.015) in MMVD group which showed eccentric cardiac hypertrophy, up-regulation of cfa-miR-346 (FC = 2.74, p = 0.032), down-regulation of cfa-miR-505 (FC = 1.56, p = 0.016) in PS group which showed concentric cardiac hypertrophy, and down-regulation of cfa-miR-30c (FC = 3.45, p = 0.013 in MMVD group; FC = 3.31, p = 0.014 in PS group) and cfa-let-7b (FC = 11.42, p = 0.049 in MMVD group; FC = 5.88, p = 0.01 in PS group) in both MMVD and PS groups. In addition, the unsupervised hierarchical clustering of differentially expressed microRNAs in each group resulted in complete separation of healthy dogs from dogs with heart diseases. Therefore, eleven microRNAs among 291 microRNAs were identified as differentially expressed circulating microRNAs related to MMVD or PS in dogs. This pilot study demonstrates that the microRNAs identified in this study could be possible candidates for novel biomarker or therapeutic target related to cardiac hypertrophy in dogs.


2021 ◽  
Author(s):  
Karin Sanders ◽  
Anouk Veldhuizen ◽  
Hans S. Kooistra ◽  
Adri Slob ◽  
Elpetra P.M. Timmermans-Sprang ◽  
...  

Canine Cushing′s syndrome (hypercortisolism) can be caused by a pituitary tumor (pituitary-dependent hypercortisolism; PDH) or a cortisol-secreting adrenocortical tumor (csACT). For both cases, noninvasive biomarkers that could pre-operatively predict the risk of recurrence after surgery would greatly impact clinical decision making. The aim of this study was to determine whether circulating microRNAs (miRNAs) can be used as noninvasive biomarkers for canine Cushing′s syndrome. After a pilot study with 40 miRNAs in blood samples of healthy dogs (n = 3), dogs with PDH (n = 3) and dogs with a csACT (n = 4), we selected a total of 20 miRNAs for the definitive study. In the definitive study, these 20 miRNAs were analyzed in blood samples of healthy dogs (n = 6), dogs with PDH (n = 19, pre- and post-operative samples) and dogs with a csACT (n = 26, pre-operative samples). In dogs with PDH, six miRNAs (miR-122-5p, miR-126-5p, miR-141-3p, miR-222-3p, miR-375-3p and miR-483-3p) were differentially expressed compared to healthy dogs. Of one miRNA, miR-122-5p, the expression levels did not overlap between healthy dogs and dogs with PDH (p = 2.9x10-4), significantly decreased after hypophysectomy (p = 0.013), and were significantly higher (p = 0.017) in dogs with recurrence (n = 3) than in dogs without recurrence for at least one year after hypophysectomy (n = 7). In dogs with csACTs, two miRNAs (miR-483-3p and miR-223-3p) were differentially expressed compared to healthy dogs. Additionally, miR-141-3p was expressed significantly lower (p = 0.009) in dogs with csACTs that had a histopathological Utrecht score of ≥ 11 compared to those with a score of < 11. These results indicate that circulating miRNAs have the potential to be noninvasive biomarkers in dogs with Cushing′s syndrome that may contribute to clinical decision-making.


2013 ◽  
Vol 35 ◽  
pp. 561-566 ◽  
Author(s):  
Ali Sheikh Md Sayed ◽  
Ke Xia ◽  
Tian-Lun Yang ◽  
Jun Peng

Rapid and correct diagnosis of acute myocardial infarction (AMI) plays a crucial role in saving patients' life. Although some biomarkers (such as cardiac troponin and creatine kinase) are available for AMI diagnosis so far, there is still a clinical need for novel biomarkers, which can reliably rule in or rule out AMI immediately on admission. Circulating microRNAs (miRNAs) are a potential choice for novel biomarkers in AMI diagnosis and prognosis with high sensitivity and specificity. Circulating microRNAs are endogenous miRNAs that are detectable in whole blood, serum, or plasma in a highly stable form. Until now, around 20 circulating miRNAs were reported to be closely associated with AMI. In this minireview, we summarized recent available data on the correlation between circulating miRNAs and AMI. Some miRNAs, such as miR-208, miR-499, miR-133, and miR-1, were given special attention, since they may have a potential prospect in diagnosis and prognosis of AMI.


2021 ◽  
Vol 8 ◽  
Author(s):  
Ga-Won Lee ◽  
Min-Hee Kang ◽  
Woong-Bin Ro ◽  
Doo-Won Song ◽  
Hee-Myung Park

Galectin-3 is involved in important biological functions such as fibrogenesis and inflammation. Notably, it is associated with various diseases and plays a major role in cardiac inflammation and fibrosis. Although heart diseases are relatively common in dogs, a few studies have analyzed the circulating galectin-3 concentration in dogs with various heart diseases, including myxomatous mitral valve disease, patent ductus arteriosus, and pulmonic stenosis. The aims of the present study were to evaluate the effect of heart disease on circulating galectin-3 levels in dogs, and also to evaluate the correlation between galectin-3 concentration and conventional echocardiographic indices along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in dogs with heart diseases. The medical records and archived serum samples of 107 dogs were evaluated retrospectively. In total, 107 dogs were classified into healthy dogs (n = 8), cardiac disease (n = 26), and non-cardiac disease groups (n = 73). The circulatory galectin-3 levels were analyzed using a commercially available canine-specific galectin-3 enzyme-linked immunosorbent assay kit. This study demonstrated that dogs with heart, endocrine, and dermatologic diseases had significantly higher galectin-3 levels than healthy dogs (p = 0.009, p = 0.007, and p = 0.026, respectively). Among dogs with heart diseases, dogs with concentric cardiomyopathy had significantly increased circulatory galectin-3 levels compared with healthy dogs (p = 0.028). E′/A′ had a positive association with galectin-3 levels among conventional echocardiographic indices. Moreover, the galectin-3 concentration could predict diastolic dysfunction. In dogs with myxomatous mitral valve disease, a significantly positive correlation was revealed between galectin-3 levels and NT-proBNP levels (p = 0.007). Overall, this study demonstrates that circulatory galectin-3 levels increase in dogs with heart, endocrine, and dermatologic diseases. Moreover, this study demonstrates that galectin-3 concentration could be helpful to evaluate cardiac remodeling and diastolic function. Further large-scale research is required to evaluate the role of circulating galectin-3 in dogs with heart diseases.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3348
Author(s):  
Masahisa Ohtsuka ◽  
Kazuya Iwamoto ◽  
Atsushi Naito ◽  
Mitsunobu Imasato ◽  
Satoshi Hyuga ◽  
...  

Gastrointestinal cancer (GIC) is a common disease and is considered to be the leading cause of cancer-related death worldwide; thus, new diagnostic and therapeutic strategies for GIC are urgently required. Noncoding RNAs (ncRNAs) are functional RNAs that are transcribed from the genome but do not encode proteins. MicroRNAs (miRNAs) are short ncRNAs that are reported to function as both oncogenes and tumor suppressors. Moreover, several miRNA-based drugs are currently proceeding to clinical trials for various diseases, including cancer. In recent years, the stability of circulating miRNAs in blood has been demonstrated. This is of interest because these miRNAs could be potential noninvasive biomarkers of cancer. In this review, we focus on circulating miRNAs associated with GIC and discuss their potential as novel biomarkers.


Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1432
Author(s):  
Thaís Borges Gally ◽  
Milena Magalhães Aleluia ◽  
Grasiely Faccin Borges ◽  
Carla Martins Kaneto

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases—PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File—using the terms: “Circulating microRNAs” OR “plasma microRNAs” OR “serum microRNAs” OR “blood microRNAs” OR “cell-free microRNAs” OR “exosome microRNAs” OR “extracellular vesicles microRNAs” OR “liquid biopsy” AND “osteosarcoma” AND “diagnostic”. We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS.


2020 ◽  
Vol 12 ◽  
pp. 1759720X2095333
Author(s):  
Yi Shuai ◽  
Li Liao ◽  
Xiaoxia Su ◽  
Nanxi Sha ◽  
Xiaobo Li ◽  
...  

Aims: Osteoporosis is underdiagnosed because of the lack of a convenient diagnostic method. Circulating microRNAs (miRNAs) emerge as novel biomarkers for disease diagnosis. Here, we conducted a case-control study that included a total of 448 serum samples collected from 182 healthy participants, 132 osteopenia participants, and 134 osteoporosis patients. Methods: Circulating miRNAs dysregulated during osteoporosis were screened and analyzed in three randomly determined sub-cohorts: the discovery cohort identified 22 candidate miRNAs; the training cohort tested the candidate miRNAs and constructed Index 1, comprising five miRNAs by logistic regression, and Index 2, comprising four miRNAs, was developed by linear combination. Results: Both indices were tested in the validation cohort and showed statistically significant results in distinguishing osteoporosis patients from healthy and osteopenic patients. Moreover, Index 1 also showed improved performance over traditional bone turnover biomarkers type I pro-collagen (tPINP) and type I collagen (β-CTx). Conclusion: In conclusion, circulating miRNAs are potential biomarkers for osteoporosis. The diagnostic panel of circulating miRNAs could be a complementary method for dual-energy X-ray absorptiometry (DXA) in mass screening and routine examination to enhance the osteoporosis detection rate.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Shao-Chun Wu ◽  
Cheng-Shyuan Rau ◽  
Johnson Chia-Shen Yang ◽  
Tsu-Hsiang Lu ◽  
Yi-Chan Wu ◽  
...  

Background. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation in the presence and absence of FK506 immunosuppression.Methods. A 1 cm BALB/c donor sciatic nerve graft was transplanted into the sciatic nerve gaps created in recipient C57BL/6 mice with or without daily FK506 immunosuppression [1 mg/(kg·d)]. At 3, 7, and 14 d after nerve allotransplantation, serum samples were collected for miRNA expression analysis by Illumina small RNA deep sequencing.Results. Sequence analysis showed that the dominant size of circulating small RNAs after nerve allotransplantation was 22 nucleotides, followed by 23-nucleotide sequences. Nine upregulated circulating miRNAs (let-7e-5p, miR-101a-3p, miR-151-5p, miR-181a-5p, miR-204-5p, miR-340-5p, miR-381-3p, miR-411-5p, miR-9-5p, and miR-219-2-3p) were identified at 3 d, but none was identified at 7 or 14 d. Among them, miR-9-5p had the highest fold-change of >50-fold, followed by miR-340-5p with 38.8-fold. The presence of these nine miRNAs was not significant at 7 and 14 d after nerve allotransplantation with or without immunosuppression, showing that these miRNAs are not ideal biomarkers for monitoring rejection of deep-buried nerve allografts, a response usually observed later.Conclusions. We identified nine upregulated circulating miRNAs, which may have a biological function, particularly during the early stages after nerve allotransplantation under FK506 immunosuppression.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Yan Liu ◽  
Shaoliang Chen ◽  
Junjie Zhang ◽  
Shoujie Shan ◽  
Liang Chen ◽  
...  

Recent evidence suggests that cell-derived circulating miRNAs may serve as the biomarkers of cardiovascular diseases. However, no study has investigated the potential of circulating miRNAs as biomarker for coronary bifurcation lesion. In this study, we aimed to characterize the miRNA profiles that could distinguish coronary bifurcation lesion and identify potential miRNAs as biomarkers of coronary bifurcation lesion. We employed miRNA microarray to screen serum miRNAs profiles of patients with coronary bifurcation lesion and coronary nonbifurcation lesions. We identified 197 miRNAs differentially expressed, including 150 miRNAs upregulated and 47 miRNAs downregulated. We chose 3 miRNAs with significant differences for further testing in 200 patients. RT-PCR analysis of serum samples confirmed that miR30d was upregulated and miR1246 was downregulated in the serum of coronary bifurcation lesion patients compared with nonbifurcation lesion patients. Our findings suggest that these miRNAs may have a role in the pathogenesis of coronary bifurcation lesion and may represent novel biomarkers for the diagnosis and prognosis of coronary bifurcation lesion.


2018 ◽  
Vol 54 (15) ◽  
pp. 1909-1912 ◽  
Author(s):  
Kai Ling ◽  
Hongyan Jiang ◽  
Xue Huang ◽  
Yang Li ◽  
Juanjuan Lin ◽  
...  

We developed a microplate-based enhanced chemiluminescence system for the direct detection of circulating miRNAs. The system exhibited a high target sensitivity and specificity, with a detection limit of 3.02 fM.


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