scholarly journals Classification of potential pathways affecting the VEGF pathway in glioblastoma multiforme (GBM) recurrent: A bioinformatics study based on differentially expressed- microRNAs

2021 ◽  
Author(s):  
Morteza Hadizadeh ◽  
Ramin Soltani ◽  
Taimour Langaee ◽  
Marziye Shad pirouz ◽  
M. R. Mozafari ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Mapk Pathway ◽  
R Package ◽  
Differentially Expressed ◽  
Kegg Database ◽  
Vegf Signaling ◽  
Differentially Expressed Mirnas ◽  
Vegf Pathway ◽  
Vegf Signaling Pathway

Abstract Glioblastoma multiforme (GBM) resistance to anti-angiogenesis drugs results in recurrence of the disease which leads to death. The resistance to anti-angiogenesis drugs that target the VEGF pathway is due to the influence of other pathways. This study aimed to identify and classify the pathways that are related to the VEGF pathway in GBM recurrent. The identification of differentially expressed miRNAs (DEmiRNAs) based on GBM GSE profiles (GSE32466) were carried out using a LIMMA R package and VEGF pathway genes in the KEGG database. Pathways related to DEmiRNAs and VEGF pathway genes were discovered by DIANA-miRPath v3.0, NetworkAnalyst and ToppGene databases, respectively. Inhibitory or activity affecting pathways relating to VEGF pathway were obtained based on XTalkDB database. The classification was determined by the KEGG database. There were 1014 genes that were found to have interaction with VEGF signaling pathway genes. One hundred ninteen pathways were achieved which have overlapping genes with the VEGF pathway genes. The MAPK pathway had the most in common genes with the VEGF pathway (39 genes). A total of 91 pathways were identified in 24 different classes. Several pathways significantly affect the VEGF pathway. Hence, it seems necessary to achieve new targets for combination therapies for GBM.

scholarly journals Prediction of Differentially Expressed miRNAs as Potential Biomarkers for Aniridia-Associated Keratopathy based on Expression Profile Analyses

2020 ◽  
Author(s):  
Daowei Zhang ◽  
Shenghai Zhang
Keyword(s):  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
R Package ◽  
Differentially Expressed ◽  
Diagnosis And Treatment ◽  
Mirna Targets ◽  
Differentially Expressed Mirnas ◽  
New Ideas ◽  
Potential Biomarkers

Abstract Background: Aniridia is a rare hereditary disorder that affects most structures of the eyes. This autosomal dominant disorder is caused by haploinsufficiency of Pax6, a critical gene for proper development of the eye. This study attempted to identify novel diagnostic differentially expressed miRNAs and related mRNAs to develop a deeper understanding of the molecular mechanisms and to provide new ideas for the diagnosis and treatment of aniridia-associated keratopathy (AAK). Methods: The miRNA and mRNA expression data were downloaded from GEO for differential expression analysis. R programs, WGCNA, and miRNA targets were used to identify differentially expressed genes (DEGs). The R package was used to screen candidate miRNAs as potential biomarkers, and predicted targets and DEG intersections were determined. A regulatory network between optimal differentially expressed miRNA and DEGs was then constructed. Function analysis and pathway enrichment of miRNA and mRNA were both performed. In addition, transcription factors (TFs) of differential miRNAs and molecular compounds that may be efficient were predicted.Results: We used three methods to identify DEGs: 509 differential genes were screened by R, 1522 by WGCNA, and 732 by prediction of different miRNA targets. In total, 18 DEGs were found, encompassing 9 upregulated genes and 9 downregulated genes. Eight differentially expressed miRNAs were identified using the R package: five were upregulated and three were downregulated. Among them, three miRNAs (miR-204-5p, miR-224-5p, and miR-30a-5p) were considered optimal potential biomarkers, and their regulatory network with DEGs was created by Cytoscape. IL-4-mediated signaling events were the most enriched signaling pathways. Based on these DEGs, CHL1 and SOCS3 were most closely associated with clinical characteristics, which related to sex and stage separately.Conclusions: This study identified novel diagnostic differentially expressed miRNAs and related mRNAs by developing a deeper understanding of the molecular mechanisms, based on that we provided new ideas for the diagnosis and treatment of AAK.

scholarly journals Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yong Zhao ◽  
Hao Wang ◽  
Ming Lu ◽  
Xin Qiao ◽  
Bei Sun ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Target Genes ◽  
Culture Media ◽  
Mapk Pathway ◽  
Acinar Cells ◽  
Differentially Expressed ◽  
Pancreatic Acinar Cells ◽  
Supernatant Fraction ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas

Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway.

scholarly journals Identification of TIMP2 and RAX as key regulators in chemosensitive osteosarcoma

2020 ◽  
Author(s):  
HuaBin Wang ◽  
Yuanxiang Liu ◽  
Haitao Zeng
Keyword(s):  
Cell Proliferation ◽  
Cell Survival ◽  
Differentially Expressed ◽  
Cell Counting ◽  
Regulation Mechanism ◽  
Rt Pcr ◽  
P Values ◽  
Vegf Signaling ◽  
Differentially Expressed Mirnas ◽  
And Function

Abstract Background This study is trying to investigate the regulation mechanism of chemosensitive osteosarcoma. mRNA and miRNA profiles were explored between chemosensitive and chemoresistant osteosarcoma patients based on GSE39058 dataset. IPA was used for pathway and function enrichment. Another dataset GSE21257 with clinical characteristics was used for survival analysis, and 68 new enrolled osteosarcoma patients with chemotherapy responses were used for RT-PCR validation. Finally, lentiviruses infected U-2 OS cells were subjected to cell counting and real-time cell analyzer.Results A total of 567 differentially expressed genes and 34 differentially expressed miRNAs were screened out. These genes mainly involved in the biology functions of cell survival and cell proliferation, and enriched in the pathways of VEGF signaling, Paxillin signaling, and Inhibition of matrix matalloproteases. In 53 validation osteosarcoma patients from GSE21257, high-expression of TIMP2 and BAX, two common genes among the enriched biology functions, have favorable prognosis with p-values 0.052 and 0.027 respectively. In the 68 new enrolled patients, both TIMP2 and BAX were RT-PCR validated to be high-expressed in chemosensitive group with p-values 0.04 and 0.003 respectively. In addition, cell count and cell index either in TIMP2 or BAX infected U-2 OS cells were smaller compared with control cells within four consecutive days.Conclusions In summary, the biology functions of cell survival and cell proliferation were identified to be mainly inhibited in chemosensitive osteosarcoma patients. Two up-regulated genes, TIMP2 and BAX, were validated to be important regulators of cell proliferation and cell apoptosis in chemosensitive group. Further experimental evidences are still needed to consolidate this results.

scholarly journals MicroRNA-183 Suppresses Neuropathic Pain and Expression of AMPA Receptors by Targeting mTOR/VEGF Signaling Pathway

2017 ◽  
Vol 41 (1) ◽  
pp. 181-192 ◽  
Author(s):  
Xiaojuan Xie ◽  
Ligang Ma ◽  
Kai Xi ◽  
Wei Zhang ◽  
Dongmei Fan
Keyword(s):  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Ampa Receptors ◽  
Vegf Receptors ◽  
Vegf Signaling ◽  
Regulation Mechanisms ◽  
Vegf Pathway ◽  
Cci Model ◽  
Nerve System ◽  
Vegf Signaling Pathway

Background: Neuropathic pain is a type of chronic pain that results from dysfunctions of the somatosensory nerve system. This study was aimed to investigate the effect of mTOR/VEGF signaling pathway on neuropathic pain and the regulation mechanisms of miR-183 on AMPA Receptors through mTOR/VEGF signaling pathway. Methods: Chronic compress injury (CCI) model was constructed in the current study, we used paw withdrawal mechanic threshold (PWMT) and paw withdrawal thermal latency (PWTL) to observe mTOR and VEGF receptors. Dual luciferase analysis, western blot and qRT-PCR were also applied to complete this experiment. Results: It was observed that the inhibition of mTOR and VEGF receptors could significantly relieve neuropathic pain in the CCI model. Moreover mTOR was confirmed as the direct target of miR-183. Furthermore, miR-183 could modulate VEGF through regulating mTOR expressions. We also found the expressions of AMPA receptors (i.e. GluR1 and GluR2), located in the downstream of mTOR/VEGF signaling pathway, were significantly upregulated when miR-183 was downregulated or when the mTOR/VEGF signaling pathway was activated. Conclusion: The inhibition of mTOR or VEGF receptors can significantly relieve neuropathic pain, and the upregulation of miR-183 can suppress AMPA receptors by inhibiting mTOR/VEGF pathway.

scholarly journals The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ke Li ◽  
Xiaoming Chen ◽  
Jing Zhong ◽  
Hehe Ye ◽  
Shujing Zhang ◽  
...  
Keyword(s):  
Influenza A ◽  
High Throughput Sequencing ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Kegg Database ◽  
Qrt Pcr ◽  
Go Enrichment ◽  
Differentially Expressed Mirnas ◽  
Therapeutic Mechanisms ◽  
Go Enrichment Analysis

Abstract Background MicroRNAs (miRNAs) play vital roles in acute inflammatory and antiviral responses during influenza A virus (IAV) infection. The Xijiao Dihuang decoction combined with Yinqiao powder (XDY) is applied to remedy viral pneumonia in China and its therapeutic efficacy in pneumonic mice challenged with IAV was demonstrated; however, the underlying mechanisms remain elusive. Thus, this study aimed to explore the miRNA-mRNA profiles in the lungs of IAV-infected mice and investigate the therapeutic mechanisms of XDY involving miRNAs and associated pathways. Methods We detected the cellular miRNA contents in the lungs of mice treated with XDY (23 g/kg/d) for A/FM/1/47 (H1N1) (FM1) infection at 4 days postinoculation (dpi) and 7 dpi. MiRNA and mRNA high-throughput sequencing analyses, and miRNA and mRNA qRT-PCR analyses were used to detect and verify the relevant miRNAs and mRNAs. Conjoint analysis, GO enrichment analysis, and KEGG database analysis were applied to identify the miRNA-mRNA regulatory relationships. Results The quantities of differentially expressed miRNAs and mRNAs were upregulated over time. The data showed that 104 miRNAs and 3485 mRNAs were differentially expressed after challenge with FM1 on day 4, while 191 miRNAs and 6126 mRNAs were differentially expressed on day 7. The GO enrichment analysis and KEGG database data showed that the differentially expressed miRNAs and mRNAs were mainly enriched in JNK activity, MAPK phosphatase activity, and the TLR, Jak-STAT and TNF signalling pathways after treatment of FM1 infection with XDY. Generally, the expression trends of differentially expressed miRNAs and mRNAs based on the qRT-PCR results exhibited good consistency with the results of the high-throughput sequencing analysis. Conclusions MiRNAs and mRNAs were differentially expressed during FM1 infection. The therapeutic mechanisms of XDY in FM1-infected mice, might be related to regulating antiviral immunity and ameliorating excessive inflammatory responses by modulating the expression of dysregulated miRNAs and mRNAs involved in the ERK/JNK-AP-1, and IFN-β/STAT signalling pathways.

scholarly journals Identification and Bioinformatics Analysis of Differentially Expressed Milk Exosomal Micrornas in Milk Exosomes of Heat-Stressed Holstein Cows

2021 ◽  
Author(s):  
Yue Wang ◽  
Jian Fang ◽  
Han-Fang Zeng ◽  
Hui-Xia Li ◽  
Kun-Lin Chen
Keyword(s):  
Heat Stress ◽  
Dairy Cows ◽  
Mapk Pathway ◽  
Genetic Material ◽  
Tissue Growth ◽  
Differentially Expressed ◽  
Holstein Cows ◽  
Small Rna Sequencing ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas

Abstract Background In summer, heat stress is one of the primary reasons for the compromised health and low milk productivity of dairy cows. Hyperthermia affects milk synthesis and secretion in the mammary glands of dairy cows. As molecules for intercellular communication, milk-derived exosomes carry genetic material, proteins and, lipids, playing a crucial role in mammary tissue growth and milk synthesis in dairy cows. The aim of this study was to explore the milk exosomal miRNAs profile of heat-stressed and normal Holstein cows. Results We isolated and identified milk exosomes to screening for differentially expressed miRNAs using small RNA sequencing. Then, TargetScan and miRanda algorithms were used to predict the putative targets of the differentially expressed miRNAs, whereas GO and KEGG pathway enrichment analyses were performed for the differentially expressed miRNA-target genes. Our results showed that 215 miRNAs were significantly differentially expressed in heat-stressed milk exosomes, of which one was up-regulated and 214 were significantly downregulated. GO and KEGG enrichment analyses indicated that differentially expressed miRNAs might play a role in apoptosis, autophagy, and the p38 MAPK pathway. qRT-PCR assay verified that the expression of miRNAs was consistent with the sequencing results, warranting further verification of their specific targets of action. Conclusions In conclusion, changes in the miRNA expression profile of milk exosomes indicated the role of exosomal miRNAs in regulating heat stress resistance and apoptosis in dairy cows. Our results suggested that milk-derived exosomal miRNAs could increase mammary gland resistance to heat stress, thereby enhancing milk synthesis in dairy cows.

Differentially expressed miRNAs in spindle cell oncocytoma of the pituitary gland

2019 ◽  
Author(s):  
Lilla Krokker ◽  
Gabor Nyirő ◽  
Lilla Reininger ◽  
Otto Darvasi ◽  
Nikolette Szucs ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Spindle Cell ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Spindle Cell Oncocytoma

Bioinformatics Analysis Reveals Functions of MicroRNAs in Rice Under the Drought Stress

2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen
Keyword(s):  
Drought Stress ◽  
Target Genes ◽  
Hot Spot ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Promising Tool ◽  
Differentially Expressed Mirnas ◽  
Aba Biosynthesis

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.

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