Serum microRNA Expression Profiling in Malaria Patients and Bioinformatic Analysis of Hsa-miR-106b-5p

Abstract BackgroundMalaria, caused by Plasmodium, is one of the three major infectious diseases that seriously endangers public health. Resistance to anti-malarial drugs and insecticides has made the prevention and control of malaria shown little improvement in the last four years. This study aimed to explore the changes in microRNA (miRNA) expression profiling of malaria patient and predict malaria-related miRNA by bioinformatics methods to provide theoretical basis for further verification of the correlation between specific miRNAs and immune regulation of malaria.MethodsSerum of patients infected by Plasmodium falciparum and healthy people from Myanmar border area was collected. miRNA expression profiling was obtained by RT-qPCR. Then the differentially expressed miRNA was screened and target genes were predicted by four miRNA databases (TargetScan, DIANA-microT, miRDB, and miRTarbase) and an intersection of target genes was obtained by Venn analysis. GO and KEGG analysis were performed for the overlapping target genes via Metascape. The results were further visualized by Cytoscape. Finally, Protein-protein interaction (PPI) network of predicted overlapping target genes was built by STRING.ResultsAmong the 341 tested serum miRNAs, 64 were differentially expressed in malaria patients (P<0.05), 27 miRNAs were up-regulated and 37 miRNAs were down-regulated. The miRNA with the most significant difference was hsa-miR-106b-5p (FC=14.871, adjusted.P.value<0.01); GO and KEGG analysis found that its overlapping predicted target gene set was remarkably enriched in biological functions such as GO:0007264~small GTPase mediated signal transduction, GO:0051056~regulation of small GTPase mediated signal transduction, GO:0051020~GTPase binding, GO:0048514~blood vessel morphogenesis(P<0.01) and signal pathway such as hsa04144: Endocytosis, hsa01521:EGFR tyrosine kinase inhibitor resistance, hsa05212:Pancreatic cancer (P<0.01); Besides, a PPI network containing 39 predicted target genes of hsa-miR-106b-5p was constructed, and 5 hub genes VEGFA, STAT3, RACGAP1, OCRL, and RBBP7 have been selected.ConclusionThe bioinformatics analysis results indicated that hsa-miR-106b-5p has a great relationship with malaria, it plays a part in inhibiting the emergence of ARTs resistance in Plasmodium and tumor progression, which may be achieved by regulating vascular morphogenesis, endocytosis, and VEGFA. The underlying mechanism needs to be further elucidated. We believe that this finding will facilitate an in-depth research on the association between malaria and miRNA.

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Identification of Differentially Expressed MicroRNAs in Osteosarcoma

Sarcoma ◽

10.1155/2011/732690 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 90

Author(s):

Rishi R. Lulla ◽

Fabricio F. Costa ◽

Jared M. Bischof ◽

Pauline M. Chou ◽

Maria de F. Bonaldo ◽

...

Keyword(s):

High Throughput ◽

Mirna Expression ◽

Expression Profiling ◽

Differentially Expressed ◽

Pcr Analysis ◽

Osteosarcoma Cell ◽

Human Osteoblasts ◽

Normal Human ◽

Mirna Expression Profiling

A limited number of reports have investigated the role of microRNAs in osteosarcoma. In this study, we performed miRNA expression profiling of osteosarcoma cell lines, tumor samples, and normal human osteoblasts. Twenty-two differentially expressed microRNAs were identified using high throughput real-time PCR analysis, and 4 (miR-135b, miR-150, miR-542-5p, and miR-652) were confirmed and validated in a different group of tumors. Both miR-135b and miR-150 have been previously shown to be important in cancer. We hypothesize that dysregulation of differentially expressed microRNAs may contribute to tumorigenesis. They might also represent molecular biomarkers or targets for drug development in osteosarcoma.

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Analysis of Predictive Value and Target Gene Prediction of Serum Micro-RNA-205 in Diagnosis and Prognosis of Prostate Cancer

Nanoscience and Nanotechnology Letters ◽

10.1166/nnl.2020.3100 ◽

2020 ◽

Vol 12 (2) ◽

pp. 196-201

Author(s):

Xiangnan Hu ◽

Xiaoliang Dou ◽

He Wang ◽

Jinbo Sun ◽

Bo Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Mirna Expression ◽

Predictive Value ◽

Expression Profiling ◽

Target Genes ◽

Micro Rna ◽

Serum Samples ◽

Serum Mirna ◽

Diagnosis And Prognosis ◽

Mirna Expression Profiling

The aim of this study was to explore the predictive value of serum micro-RNA (miRNA)-205 in the diagnosis and prognosis of prostate cancer, and analyze miRNA-205 target genes and functions. Eight patients diagnosed with prostate cancer or benign prostatic hyperplasia (BPH) that were treated in January 2011 were selected. The serum samples between the two groups were analyzed for miRNA expression profiling, and the differentially expressed miRNA-205 was selected for further analysis. The serum samples of 64 patients with prostate cancer and 20 patients with BPH from March 2011 to March 2013 were collected for qPCR verification. We evaluated the correlation between miRNA-205 expression level and clinicopathological data of 64 patients with prostate cancer and its prognostic value. Finally, through bioinformatic analysis, target genes of miRNA-205 were predicted, and gene ontology (GO) analysis and signal pathway analysis were performed. A total of 657 differential miRNAs were screened from miRNA expression profiling. Compared with patients with BPH, miRNA-205 showed lower expression in the serum of patients with prostate cancer. Serum miRNA-205 + PSA combined had the strongest predictive ability, 0.805. The expression level of miRNA-205 in the patients with a Gleason score ≥7 was lower than that in patients with a Gleason score <7, Low miRNA-205 expression was associated with bone metastasis and higher T stage ratings, and the 5-year overall survival rate of the low miRNA-205 expression group was lower than the high miRNA-205 expression group. A total of 27 miRNA-205 target genes were predicted. The target genes of miRNA-205 are mainly enriched in biological functions such as cell adhesion and GTP kinase activity. The target genes of miRNA-205 are mainly enriched in Axon guidance and signal transduction by L1 and other signal pathways. In this study, serum miRNA-205 was successfully identified as a potential noninvasive serum marker for diagnosis and prognosis of prostate cancer, which will be helpful for future clinical research and prostate cancer drug target design.

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Probe into the Target and Mechanism of Jianpi Xiaoke Prescription for Treating Type 2 Diabetes Mellitus through miRNA Expression Profiling

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/7370350 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Qiuyue Guo ◽

Yunsheng Xu ◽

Jie Li ◽

Dan Luo ◽

Jun Li ◽

...

Keyword(s):

Type 2 Diabetes ◽

Signaling Pathways ◽

Mirna Expression ◽

Expression Profiling ◽

Target Genes ◽

Cell Function ◽

Control Group ◽

Sequencing Data ◽

Mirna Expression Profiling

Object. To probe into the target and molecular mechanism of Jianpi Xiaoke (JPXK) prescription in the treatment of type 2 diabetes through high-throughput microRNA (miRNA) sequencing. Methods. Ten of the 31 SPF male Wistar rats were randomly taken as the control group; the remaining rats were fed a high-sugar and high-fat diet, combined with Streptozotocin (STZ, 35 mg/kg) that induced a type 2 diabetes model. The model rats were randomly divided into model groups (n = 11) and the JPXK group (n = 10). After 8 weeks of JPXK intervention, we detected the function of islet cells through HE staining and ELISA. High-pass sequencing technology was adopted to identify the differential expression of miRNA to explore the target of JPXK treatment, assess the relevant target genes, conduct functional analysis, and lastly verify the sequencing data by qRT-PCR. Results. After treatment, FPG, FINS, and HOMA-IR levels of the treatment group improved significantly compared with those of the control group ( P < 0.05 ). Among the miRNAs differentially expressed between the model group and the control group, there were 7 reversals after JPXK treatment, including miR-1-3p, miR-135a-5p, miR-181d-5p, miR-206-3p, miR-215, miR-3473, and miR-547-3p (log2FC ≥ 1 or ≤ −1, P < 0.05 ). Besides, the 1810 target genes associated with these 7 miRNAs were assessed by multiMiR. According to the results of the GO and KEGG analyses, they were associated with biological processes (e.g., glucose transport and fat cell formation), and it covered multiple signaling pathways, capable of regulating islet cell function (e.g., MAPK, PI3K-Akt, Ras, AMPK, and HIF-1 signaling pathways). The PCR verification results were consistent with the sequencing results. Conclusion. This discovery interpreted the potential therapeutic targets and signaling pathways of JPXK prescription against T2DM based on miRNA expression profiling. In conclusion, our research provided novel research insights into traditional Chinese medicine (TCM) treatment of diabetes.

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Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data

Cellular Physiology and Biochemistry ◽

10.1159/000493033 ◽

2018 ◽

Vol 49 (2) ◽

pp. 678-695 ◽

Cited By ~ 9

Author(s):

Zhigang Zhang ◽

Bing Pan ◽

Shaocheng Lv ◽

Zhiwei Ji ◽

Qian Wu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Mirna Expression ◽

Expression Profiling ◽

Target Genes ◽

Diagnostic Value ◽

The Cancer Genome Atlas ◽

Systematic Evaluation ◽

Cancer Genome Atlas ◽

Mirna Expression Profiling ◽

Genome Atlas

Background/Aims: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies. Methods: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools. Results: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59–0.93], and AUC: 0.84 [95% CI 0.73–0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region. Conclusion: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.

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Identification of Transcriptional Markers and microRNA–mRNA Regulatory Networks in Colon Cancer by Integrative Analysis of mRNA and microRNA Expression Profiles in Colon Tumor Stroma

Cells ◽

10.3390/cells8091054 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1054 ◽

Cited By ~ 4

Author(s):

Md. Nazim Uddin ◽

Mengyuan Li ◽

Xiaosheng Wang

Keyword(s):

Colon Cancer ◽

Mirna Expression ◽

Expression Profiling ◽

Regulatory Networks ◽

Tumor Stroma ◽

Receptor Interaction ◽

Colon Tumor ◽

Ppi Network ◽

Hub Genes ◽

Mirna Expression Profiling

The aberrant expression of microRNAs (miRNAs) and genes in tumor microenvironment (TME) has been associated with the pathogenesis of colon cancer. An integrative exploration of transcriptional markers (gene signatures) and miRNA–mRNA regulatory networks in colon tumor stroma (CTS) remains lacking. Using two datasets of mRNA and miRNA expression profiling in CTS, we identified differentially expressed miRNAs (DEmiRs) and differentially expressed genes (DEGs) between CTS and normal stroma. Furthermore, we identified the transcriptional markers which were both gene targets of DEmiRs and hub genes in the protein–protein interaction (PPI) network of DEGs. Moreover, we investigated the associations between the transcriptional markers and tumor immunity in colon cancer. We identified 17 upregulated and seven downregulated DEmiRs in CTS relative to normal stroma based on a miRNA expression profiling dataset. Pathway analysis revealed that the downregulated DEmiRs were significantly involved in 25 KEGG pathways (such as TGF-β, Wnt, cell adhesion molecules, and cytokine–cytokine receptor interaction), and the upregulated DEmiRs were involved in 10 pathways (such as extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer). Moreover, we identified 460 DEGs in CTS versus normal stroma by a meta-analysis of two gene expression profiling datasets. Among them, eight upregulated DEGs were both hub genes in the PPI network of DEGs and target genes of the downregulated DEmiRs. We found that three of the eight DEGs were negative prognostic factors consistently in two colon cancer cohorts, including COL5A2, EDNRA, and OLR1. The identification of transcriptional markers and miRNA–mRNA regulatory networks in CTS may provide insights into the mechanism of tumor immune microenvironment regulation in colon cancer.

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Comparative miRNA Expression Profiling of Circulating Exosomes From MGUS and Smoldering Multiple Myeloma Patients

Blood ◽

10.1182/blood.v120.21.3975.3975 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3975-3975

Author(s):

Salomon Manier ◽

Erica N Boswell ◽

Antonio Sacco ◽

Patricia Maiso ◽

Ranjit Banwait ◽

...

Keyword(s):

Electron Microscopy ◽

Bone Marrow ◽

Mirna Expression ◽

Expression Profiling ◽

Advisory Board ◽

Immunogold Labeling ◽

Differentially Expressed ◽

Mirna Expression Profiling ◽

Lower Expression

Abstract Abstract 3975 Introduction. Exosomes are small vesicles (50–100 nm) of endocytic origin, which are released in the extra-cellular milieu by several cell types. It is known that cell-to-cell communication is partially mediated by exosomes. The role of exosomes has been shown in tumor progression, due to their ability to carry and transfer microRNAs (miRNAs) to the recipient cells. In this study, we sought to examine the role of circulating exosomes in modulating transition from a monoclonal gammopathy of undermined significance (MGUS) stage to a smoldering myeloma (SMM) stage. Method. Exosomes were collected from peripheral blood obtained from healthy individuals (n=4), MGUS patients (n=4) and SMM patients (n=4), using ultracentrifugation; and further studied by using electron microscopy and immunogold labeling for the detection of CD63 and CD81. miRNA profiling has been performed using nCounter miRNA expression assay (Nanostring® Technologies, Seattle WA). Bioinformatic software tools (TargetScan, MIRDB) were used to predict the target genes of identified miRNA and define their function. Results. Circulating exosomes were studied at ultrastructural level showing positivity for CD81 and CD63, as demonstrated by immunogold labeling and electron microscopy. We identified 16 miRNAs differentially expressed in circulating exosome obtained from MGUS patients compared to healthy subjects (p < 0.05): specifically, higher expression of miR-450a, -30e, -125a, -300 and lower expression of miR-185, -150, -98 were observed in MGUS- compared to heatly individual-derived circulating exosomes. Interestingly, miR-30e and -150 are important for modulation of NK cell activity by targeting perforin and c-Myb, respectively. We furthermore compared the miRNA expression profiling between MGUS and SMM circulating exosomes; and found 11 miRNAs differentially expressed (p < 0.05). Specifically, higher expression of miR-107 and lower expression of miR-28, -32, -548a, -939, -99a, -345, -125a, -587, -323b and -92a were observed in SMM- compared to MGUS-derived circulating exosomes. Among the de-regulated miRNAs, miR-99a, -345, -92a and -28 are known to act as tumor suppressors in prior publications. Moreover, predicted targets for miR-107 include genes involved in molding the bone marrow microenvironment. Indeed, miR-107 is known to decrease hypoxia-inducible factor-1 β (HIF-1β), miR-125a correlated with the expression level of matrix metalloproteinase 11 (MMP11), and vascular endothelial growth factor A (VEGF-A) and miR-548a regulates the expression of MMP2. Conclusion. These findings indicate that circulating exosomes differ between normal, MGUS and SMM patients, and could potentially be involved in modulating the host microenvironment for specific homing of clonal plasma cells to the bone marrow; thus providing a better understanding of the epigenetic changes responsible for the transition from an MGUS stage to a SMM stage. Disclosures: Ghobrial: Millennium: Advisory Board Other; Novartis: Advisory Board, Advisory Board Other.

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Transcriptomic and epigenomic remodeling occurs during vascular cambium periodicity in Populus tomentosa

Horticulture Research ◽

10.1038/s41438-021-00535-w ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Bo Chen ◽

Huimin Xu ◽

Yayu Guo ◽

Paul Grünhofer ◽

Lukas Schreiber ◽

...

Keyword(s):

Signal Transduction ◽

Plant Hormone ◽

Target Genes ◽

Populus Tomentosa ◽

Differentially Expressed ◽

Vascular Cambium ◽

Differentially Methylated Region ◽

Gene Body Methylation ◽

Transcription Analysis ◽

Global Methylation

AbstractTrees in temperate regions exhibit evident seasonal patterns, which play vital roles in their growth and development. The activity of cambial stem cells is the basis for regulating the quantity and quality of wood, which has received considerable attention. However, the underlying mechanisms of these processes have not been fully elucidated. Here we performed a comprehensive analysis of morphological observations, transcriptome profiles, the DNA methylome, and miRNAs of the cambium in Populus tomentosa during the transition from dormancy to activation. Anatomical analysis showed that the active cambial zone exhibited a significant increase in the width and number of cell layers compared with those of the dormant and reactivating cambium. Furthermore, we found that differentially expressed genes associated with vascular development were mainly involved in plant hormone signal transduction, cell division and expansion, and cell wall biosynthesis. In addition, we identified 235 known miRNAs and 125 novel miRNAs. Differentially expressed miRNAs and target genes showed stronger negative correlations than other miRNA/target pairs. Moreover, global methylation and transcription analysis revealed that CG gene body methylation was positively correlated with gene expression, whereas CHG exhibited the opposite trend in the downstream region. Most importantly, we observed that the number of CHH differentially methylated region (DMR) changes was the greatest during cambium periodicity. Intriguingly, the genes with hypomethylated CHH DMRs in the promoter were involved in plant hormone signal transduction, phenylpropanoid biosynthesis, and plant–pathogen interactions during vascular cambium development. These findings improve our systems-level understanding of the epigenomic diversity that exists in the annual growth cycle of trees.

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Identification of novel MiRNAs and MiRNA expression profiling during grain development in indica rice

BMC Genomics ◽

10.1186/1471-2164-13-264 ◽

2012 ◽

Vol 13 (1) ◽

pp. 264 ◽

Cited By ~ 49

Author(s):

Ying Lan ◽

Ning Su ◽

Yi Shen ◽

Rongzhi Zhang ◽

Fuqing Wu ◽

...

Keyword(s):

Mirna Expression ◽

Expression Profiling ◽

Indica Rice ◽

Grain Development ◽

Mirna Expression Profiling

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Left-Sided Colorectal Cancer Distinct in Indigenous African Patients Compared to Other Ethnic Groups in South Africa.

10.21203/rs.3.rs-845611/v1 ◽

2021 ◽

Author(s):

M. McCabe ◽

C. Penny ◽

P. Magangane ◽

S. Mirza ◽

Y. Perner

Keyword(s):

Colorectal Cancer ◽

South Africa ◽

Ethnic Groups ◽

Mirna Expression ◽

Expression Profiling ◽

Expression Patterns ◽

Molecular Characteristics ◽

Anatomical Site ◽

Molecular Features ◽

Mirna Expression Profiling

Abstract Introduction: A large proportion of indigenous African (IA) colorectal cancer (CRC) patients in South Africa are young (<50years), with no unique histopathological or molecular characteristics. Anatomical site as well as microsatellite instability (MSI) status have shown to be associated with different clinicopathological and molecular features. This study aimed to ascertain key histopathological and miRNA expression patterns in microsatellite stable (MSS) and low-frequency MSI (MSI-L) patients, to provide insight into the mechanism of the disease. Methods: A retrospective cohort (2011-2015) of MSS/MSI-L CRC patient samples diagnosed at Charlotte Maxeke Johannesburg Academic Hospital was analyzed. Samples were categorized by site [Right colon cancer (RCC) versus left (LCC)], ethnicity [IA versus other ethnic groups (OEG)] and MSI status (MSI-L vs MSS). T-test, Fischer’s exact and Chi-square tests were conducted. Additional miRNA expression profiling was performed on IA patient samples. Results: IA patients with LCC demonstrated an increased prevalence in males, sigmoid colon, signet-ring-cell morphology, MSI-L with BAT25/26 marker instability and advanced disease association. MiRNA expression profiling revealed unique clustering, with dysregulation of let-7 and miRNA-125. Conclusion: This study revealed distinct histopathological features for LCC, and suggests BAT25/26, miRNAs let-7a-5p and miRNA-125a/b-5p as negative prognostic markers in African CRC patients. Larger confirmatory studies are recommended.

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