scholarly journals Evaluation of altered miRNA expression pattern to predict COVID-19 severity.

Author(s):  
Swati Srivast ◽  
Iti Garg ◽  
Yamini Singh ◽  
Ramesh Meena ◽  
Anju A Hembrom ◽  
...  

Abstract Outbreak of COVID-19 pandemic in December 2019 affected millions of people globally. After substantial research, there is no specific and reliable biomarker available till date. Present study was designed to identify specific biomarkers to predict COVID-19 severity and tool for formulating treatment. A small cohort of subjects (n=43) were enrolled and categorized in four study groups; Dead (n=16), Severe (n=10) and Moderate (n=7) patients and healthy controls (n=10). Small RNA sequencing was done on Illumina platform after isolation of microRNA from peripheral blood. Differential expression (DE) of miRNA (patients groups compared to control) revealed 118 down-regulated and 103 up-regulated known miRNAs with fold change (FC) expression ≥2 folds and p≤0.05. DE miRNAs were then subjected to functional enrichment and network analysis. Bioinformatic analysis resulted in 31 miRNAs (24 Down-regulated; 7 up-regulated) significantly associated with COVID-19 having AUC>0.8 obtained from ROC curve. Seventeen out of 31 DE miRNAs have been linked to COVID-19 in previous studies. Three miRNAs, hsa-miR-147b-5p and hsa-miR-107 (down-regulated) and hsa-miR-1299 (up-regulated) showed significant unique DE in Dead patients. Another set of 4 miRNAs, hsa-miR-224-5p (down-regulated) and hsa-miR-4659b-3p, hsa-miR-495-3p and hsa-miR-335-3p were differentially up-regulated uniquely in Severe patients. Members of three miRNA families, hsa-miR-20, hsa-miR-32 and hsa-miR-548 were significantly down-regulated in all patients group in comparison to healthy controls. Thus a distinct miRNA expression profile was observed in Dead, Severe and Moderate COVID-19 patients. Present study suggests a panel of miRNAs which identified in COVID-19 patients and could be utilized as potential diagnostic biomarkers for predicting COVID-19 severity.

Genome ◽  
2019 ◽  
Vol 62 (11) ◽  
pp. 729-738 ◽  
Author(s):  
Jieping Huang ◽  
Shuzhe Wang ◽  
Xue Feng ◽  
Xiaoyan Liu ◽  
Jinhui Zhao ◽  
...  

The amount of intramuscular fat (IMF) affects the tenderness and juiciness of beef and is an important indicator of beef quality. A few miRNAs involved in IMF deposition have been identified in other livestock. However, in the buffalo, the association between miRNA and IMF has not been reported and the miRNA expression profile remains poorly understood. In this study, small RNA sequencing was performed to characterize the miRNA expression pattern in muscle and adipose tissues using the Illumina platform. A total of 108 differentially expressed (DE) miRNAs were identified, including 98 known miRNAs and 10 novel miRNAs. A qRT-PCR experiment confirmed the quality of the DE analysis. Eight DE miRNAs showed high expression in adipose tissue and a considerable expression level in muscle tissue. Functional enrichment indicated that bta-miR-148a, bta-miR-143, bta-miR-10b, bta-let-7i, bta-let-7f, bta-let-7b, bta-miR-30a-5p, and bta-miR-100 were significantly associated with adipogenesis, suggesting these as candidate regulators for IMF deposition in buffalo. However, further functional validation is required. This is the first characterization of the miRNA expression profile in the muscle and adipose tissues of buffalo. These results provide information for the identification of miRNAs with potential effects on IMF deposition in buffalo.


2019 ◽  
Vol 41 (5) ◽  
pp. 666-677 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Alessia Gallo ◽  
Viviana Costa ◽  
Giovanna Russelli ◽  
...  

Abstract Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the micro RNA (miRNA) cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and hTert immortalized umbilical vein endothelial cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment also by a specific packaging of miRNAs.


Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 970
Author(s):  
Tingting Lu ◽  
Xian Zou ◽  
Guangbin Liu ◽  
Ming Deng ◽  
Baoli Sun ◽  
...  

microRNAs (miRNAs) play a significant role in ovarian follicular maturity, but miRNA expression patterns in ovarian stroma (OS), large follicles (LF), and small follicles (SF) have been rarely explored. We herein aimed to identify miRNAs, their target genes and signaling pathways, as well as their interaction networks in OS, LF, and SF of Chuanzhong black goats at the estrus phase using small RNA-sequencing. We found that the miRNA expression profiles of LF and SF were more similar than those of OS—32, 16, and 29 differentially expressed miRNAs were identified in OS vs. LF, OS vs. SF, and LF vs. SF, respectively. Analyses of functional enrichment and the miRNA-targeted gene interaction network suggested that miR-182 (SMC3), miR-122 (SGO1), and miR-206 (AURKA) were involved in ovarian organogenesis and hormone secretion by oocyte meiosis. Furthermore, miR-202-5p (EREG) and miR-485-3p (FLT3) were involved in follicular maturation through the MAPK signaling pathway, and miR-2404 (BMP7 and CDKN1C) played a key role in follicular development through the TGF-β signaling pathway and cell cycle; nevertheless, further research is warranted. To our knowledge, this is the first study to investigate miRNA expression patterns in OS, LF, and SF of Chuanzhong black goats during estrus. Our findings provide a theoretical basis to elucidate the role of miRNAs in follicular maturation. These key miRNAs might provide candidate biomarkers for the diagnosis of follicular maturation and will assist in developing new therapeutic targets for female goat infertility.


2012 ◽  
Vol 117 (6) ◽  
pp. 1245-1252 ◽  
Author(s):  
Masashi Ishikawa ◽  
Shunsuke Tanaka ◽  
Masae Arai ◽  
Yuuki Genda ◽  
Atsuhiro Sakamoto

Background In previous studies, the authors showed that anesthetics affect the expression ratios of many genes in rat liver. microRNAs (miRNA) negatively regulate more than 30% of genes in cells, and control cell proliferation, inflammation, and metabolism. The authors hypothesized that anesthetics influence miRNA expression in the liver, and performed miRNA screening tests using TaqMan low-density arrays. Methods Rats were randomly assigned to the 2.4% sevoflurane group, the 600 µg·kg⁻¹·min⁻¹ propofol group, and the control group without anesthetics. Rats were allowed to breathe spontaneously under anesthesia for 6 h. The miRNA expression profile of the liver was analyzed, and 15 representative miRNAs were validated by quantitative real-time reverse transcriptase polymerase chain reaction. Results TaqMan low-density arrays analysis showed 46 miRNAs that were differentially expressed by anesthetics. After sevoflurane treatment, 16 miRNAs were significantly increased and 11 were significantly decreased compared with controls, whereas after propofol treatment, 31 miRNAs were increased and 8 were decreased. Twenty expressed miRNAs were common to both anesthetics, whereas three miRNAs were differentially expressed. Bland-Altman analysis was performed across the validations to compare the fold changes measured by both methods, and they were equivalent (mean difference=0.01, 95% CI=-0.26 to 0.27). This showed that the TaqMan low-density arrays results are accurate and can be confirmed using an independent experimental approach. Conclusion The results showed that anesthetics cause many miRNA expression changes, and the miRNA expression pattern was particular for each anesthetic. Further studies are needed to determine the functional consequence of miRNA modulation by anesthetics.


2009 ◽  
Vol 27 (6) ◽  
pp. 255-268 ◽  
Author(s):  
Emanuela Boštjančič ◽  
Nina Zidar ◽  
Damjan Glavač

MicroRNAs (miRNAs), small non-coding RNA molecules, are negative regulators of gene expression. Recent studies have indicated their role in various forms of cardiovascular disease. In spite of the number of miRNA microarray analyses performed, little is known about the genome-wide miRNA expression pattern in human myocardial infarction (MI). Using miRNA microarrays and bioinformatic analysis, miRNA expression was analyzed on human MI and foetal hearts compared to healthy adult hearts, to determine whether there is any similar expression pattern between MI and foetal hearts, and to identified miRNAs that have not previously been described as dysregulated in cardiovascular diseases. Of 719 miRNAs analyzed, ∼ 50% were expressed in human hearts, 77 miRNAs were absent from all tested tissues and 57 were confidently dysregulated in at least one tested group. Some expression patterns appeared to be similar in MI and foetal hearts. Bioinformatic analysis revealed 10 miRNAs as dysregulated in MI not yet related to cardiovascular disease, and 5 miRNAs previously described only in animal models of cardiovascular diseases. Finally, qRT-PCR analysis confirmed dysregulation of 7 miRNAs,miR-150, miR-186, miR-210, miR-451, and muscle-specific, miR-1 and miR-133a/b; all of these are believed to be involved in various physiological and pathological processes.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 624-624
Author(s):  
Marie Bouteloup ◽  
Aurélie Verney ◽  
Lucile Baseggio ◽  
Evelyne Callet-Bauchu ◽  
Pascale Felman ◽  
...  

Abstract Within the group of indolent B cells lymphomas derived from cells of the marginal zone, the pathogenesis of Splenic Marginal Zone Lymphoma (SMZL) remains incompletely characterized, in contrast to MALT lymphoma. However numerous findings recently contributed to a better description of this lymphoma, including its possible association with hepatitis C and the recurrence of 7q deletion. Furthermore, the peculiar pattern of Ig genes mutations and the biased usage of some segments (IGHV1-2) is suggestive of a T-independent Ag driven proliferation, at least at initial steps. The clinical heterogeneity is also marked with a lack of reproducible prognostic factors able to characterize the cases with a more aggressive course or histological transformation. MicroRNA (miRNA) are small non-coding RNA that have a post transcriptional regulation role by inhibiting translation of mRNA in protein and their abnormal expression was already found to contribute to the oncogenesis of various leukemias and lymphomas. The aim of the study was then to identify a miRNA profile of SMZL and to assess if specific miRNAs were associated with biological or clinical characteristics. MiRNA expression profile of SMZL was obtained by quantitative RT-PCR technology (Taqman microRNA Assays Human Panel, Applied Biosystems) which enabled to analyze 365 miRNAs. Six frozen spleen specimens of SMZL (including 2 cases with histological transformation) and 5 frozen specimens of non tumoral spleen (traumatic) were used to compare miRNA levels of expression (2−□□Ct method). Out of these 365 miRNAs, 95 were found to be reproducibly detectable in those samples and were further analyzed. Three miRNA were uniformly overexpressed in SMZL samples as compared to non tumor samples: miR-155 (mean fold change = 3.1), miR-451 (mean = 2.37), miR-486 (mean = 2.7). Conversly, 4 miRNAs were uniformly underexpressed: miR-127 (mean = 0.32), miR-139 (mean = 0.32), miR-335 (mean = 0.26), miR-411 (mean = 0.25). Interestingly, 1 miRNA, miR-21 was specifically found overexpressed only in the 2 transformed cases of SMZL (mean = 3.49) in comparison with the 4 non transformed cases (mean = 0.94). Those results were confirmed in a larger cohort of SMZL patients using a simplex real time PCR (Taqman microRNA Assays Human, Applied Biosystems) on frozen or paraffin embedded samples with a specific overexpression of miR-21 in 10 transformed cases (mean = 14.4), absent in the 6 non transformed cases (mean = 0.9) (Mann Whitney test: p =.0022). MiR-155 plays a key role in B cell differentiation and was already found overexpressed in other lymphomas subtypes. Little is know about the other miR overexpressed except for MiR- 21. MiR-21 is commonly overexpressed in solid tumors and the level of its expression is correlated in tumor growth and metastatic dissemination. It was also found overexpressed in chronic lymphocytic leukaemia and DLBCL (diffuse large B cell lymphoma). In opposite to DLBCL, our results seem to link miR-21’s overexpression with aggressive forms of SMZL. MiR-21 regulates multiple genes associated with apoptosis, migration and invasiveness. Altogether, these data points towards a specific miRNA expression pattern in SMZL and suggests that miR-21 could regulate important oncogenic pathways in transformed SMZL lymphomas.


2019 ◽  
Vol 67 (8) ◽  
pp. 1118-1124 ◽  
Author(s):  
Yuandong Zhu ◽  
Huan Zhu ◽  
Xiaobao Xie ◽  
Zhuojun Zheng ◽  
Yun Ling

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder which characterizes with platelet production impairment and platelet destruction increment. CD4+CD25+Foxp3+ Treg cells (Tregs) are involved in the immune pathogenesis of ITP. MicroRNAs (miRNAs) are also involved in ITP and their loss of function is shown to facilitate immune disorders. Thus, the miRNA expression profile in Tregs from ITP was analyzed in this study. We assessed the genome-wide miRNA expression profile of three newly diagnosed adult patients with ITP and three healthy controls using microarray analysis of CD4+CD25+CD127dim/− Tregs that were sorted using an immune magnetic bead kit. The miRNA microarray chip was based on miRBase 18.0 and Volcano Plot filtering software used to analyze the miRNA profile in Tregs. Distinct miRNA expression was further validated by fluorescence-based real-time quantitative PCR (qPCR). We found that 502 human miRNAs were differentially expressed (244 upregulated and 258 downregulated) in patients with ITP compared with healthy donors. We identified 37 miRNAs expressed significantly, including 26 upregulated and 11 downregulated. Among the deregulated miRNAs, three downregulated miRNAs including miR-155–5p, miR-146b-5p, and miR-142–3p were selected for qPCR verification. We confirmed that miR-155–5p, miR-146b–5p, and miR-142–3p were significantly decreased in Tregs from patients with ITP compared with healthy controls. Compared with the healthy controls, miRNAs expressed differentially in the Tregs of patients with ITP. The levels of expression of miR-155–5p, miR-146b-5p, and miR-142–3p were significantly decreased. Therefore, the deregulation of miRNAs may affect the function of Tregs in the course of ITP.


2020 ◽  
Vol 21 (6) ◽  
pp. 2128
Author(s):  
Éva Sághy ◽  
Imre Vörös ◽  
Bence Ágg ◽  
Bernadett Kiss ◽  
Gábor Koncsos ◽  
...  

Little is known about the mechanism of prediabetes-induced cardiac dysfunction. Therefore, we aimed to explore key molecular changes with transcriptomic and bioinformatics approaches in a prediabetes model showing heart failure with preserved ejection fraction phenotype. To induce prediabetes, Long-Evans rats were fed a high-fat diet for 21 weeks and treated with a single low-dose streptozotocin at week 4. Small RNA-sequencing, in silico microRNA (miRNA)-mRNA target prediction, Gene Ontology analysis, and target validation with qRT-PCR were performed in left ventricle samples. From the miRBase-annotated 752 mature miRNA sequences expression of 356 miRNAs was detectable. We identified two upregulated and three downregulated miRNAs in the prediabetic group. We predicted 445 mRNA targets of the five differentially expressed miRNAs and selected 11 mRNAs targeted by three differentially expressed miRNAs, out of which five mRNAs were selected for validation. Out of these five targets, downregulation of three mRNAs i.e., Juxtaposed with another zinc finger protein 1 (Jazf1); RAP2C, member of RAS oncogene family (Rap2c); and Zinc finger with KRAB and SCAN domains 1 (Zkscan1) were validated. This is the first demonstration that prediabetes alters cardiac miRNA expression profile. Predicted targets of differentially expressed miRNAs include Jazf1, Zkscan1, and Rap2c mRNAs. These transcriptomic changes may contribute to the diastolic dysfunction and may serve as drug targets.


Sign in / Sign up

Export Citation Format

Share Document