scholarly journals Identification and Functional Analysis of Serum Specific MiRNAs in Recurrent Aphthous Somatitis Patients With Excess-heat or Yin-deficiency

2020 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  

Abstract Background:To identity key miRNAs as signatures for recurrent aphthous stomatitis(RAS)with Excess-heat or Yin-deficiency bymiRNA microarrays. Method: Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat oryin-deficiencysyndrome and healthy individuals. CoremicroRNAs (miRNAs) were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out andgene-pathway-networks werevisualized to better understand the relationship between differentgenes and pathways.Result:(1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients ofyin-deficiency syndrome. Among them, 9 miRNAs werescreened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four randommiRNAs(hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validatedby real-time PCR method. 14 miRNAs werescreened out in yin-deficiency syndrome group(7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2)A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group.These targets were enriched inGO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enrichedGO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane andenrichedKEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway.Conclusion:Hsa-miR-20b-5p in patients with RAS could act as the novel target for syndromeclassification of the disease. It is upregulated in RAS patients with excess-heat syndrome while downregulated in patients with yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of RAS with excess-heat syndrome or yin-deficiency syndrome, respectively.

2019 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  

Abstract Background. MiRNAs has become an important regulator in many processes. The purpose of our study is to screen the key serum miRNAs of different syndrome of recurrent aphthous stomatitis (RAS), to find new biomarkers for the diagnosis of RAS and to further explore their role in the pathogenesis of RAS.Method. Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat or yin-deficiency syndrome and healthy individuals. Core miRNAs were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out and gene-pathway-networks were visualized to better understand the relationship between different genes and pathways.Result. (1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients of yin-deficiency syndrome. Among them, 9 miRNAs were screened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four random miRNAs (hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validated by real-time PCR method. 14 miRNAs were screened out in yin-deficiency syndrome group (7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2) A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group. These targets were enriched in GO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enriched GO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane and enriched KEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway .Conclusion. Hsa-miR-20b-5p in patients with RAS could act as the novel biomarker for clinical diagnosis of the disease. It is upregulated in RAS patients of excess-heat syndrome while downregulated in patients of yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of excess-heat syndrome and yin-deficiency syndrome RAS, respectively.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Min Shao

We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP) via establishing an microRNAs- (miRNA-) regulated pathway network (MRPN). Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS). Significant pathways based on differentially expressed genes (DEGs) using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC), TargetScan context score (TSCS), and probabilities of conserved targeting (PCT)). An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR) < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.


2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Wei Zhang ◽  
Feng Liang ◽  
Qingfeng Li ◽  
Hong Sun ◽  
Fei Li ◽  
...  

Abstract Background Hepatoblastoma (HB) is identified to be the most common liver malignancy which occurs in children. Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes and diseases, including HB. LncRNA MIR205 host gene (MIR205HG) has been investigated in multiple cancers, however, its role in HB remains to be elucidated. Methods MIR205HG expression was analyzed by RT-qPCR. EdU, colony formation and transwell assays were implemented to measure the biological function of MIR205HG on the progression of HB. Mechanism assays were carried out to probe into the underlying mechanism of MIR205HG in HB cells. Results MIR205HG was significantly overexpressed in HB. Moreover, MIR205HG inhibition suppressed the proliferative, migratory and invasive capacities of HB cells. Furthermore, MIR205HG competitively bound to microRNA-514a-5p (miR-514a-5p) and targeted mitogen-activated protein kinase 9 (MAPK9) to stimulate mitogen activated protein kinase (MAPK) signaling pathway. Besides, MIR205HG also served as a sponge for microRNA-205-5p (miR-205-5p) to activate the PI3K/AKT signaling pathway. Conclusion MIR205HG drives the progression of HB which might provide an efficient marker and new therapeutic target for HB.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3238-3238
Author(s):  
Xiao Li ◽  
Xu Feng ◽  
Chunkang Chang ◽  
Qi He ◽  
Wu Lingyun

Abstract Background MicroRNAs (miRNAs) are considered to play a key role in the pathogenesis of myelodysplastic syndromes (MDS). However, the effect of miRNA and targeted mRNA on signal transduction is not fully understood in MDS. Objective The objective of this study is to identify the miRNAs-regulated pathways. Methods Affymetrix GeneChip microRNA and PrimeView Array were used to analyze miRNAs and gene expression profile of CD34+ cells in 12 MDS patients and 6 healthy controls. Comprehensive bioinformatics analysis of the coordinate expression of miRNAs and mRNAs including Difference, Go, Pathway, Pathway-network, miRNA-Gene-Network and miRNA-Go-Network analysis was performed to identify the miRNAs-regulated networks. Results 1. 34 differentially expressed miRNAs (5 up- and 29 down-regulated miRNAs) and 1783 mRNAs (405 up- and 1378 down-regulated mRNAs) in CD34+ cells from MDS and Healthy controls were identified by miRNA and mRNA microarray, respectively (Fig.1). 2. 25 dysregulated miRNAs and 234 targeted mRNAs were identified by a combination of Pearson's correlation analysis and prediction by TargetScan; 394 target relationship of miRNAs was established (Fig.2). 3. Go analysis revealed that these miRNA-mRNAs pairs were involved in signal transduction, apoptotic process, DNA-dependent transcription regulation, protein phosphophoration, etc. Pathway analysis showed that MAPK, JAK/STAT and PI3K/Akt signaling pathways might be regulated by these miRNA-mRNAs pairs (Fig.3). 4. The pathway-network analysis revealed that MAPK signaling pathway, Jak-Stat signaling pathway and apoptosis signaling pathway (displayed by red cycle) located in the downstream of signal networks (Fig. 3E). Dysregulation of These pathways may be more meaningful for explaining the pathogenesis of MDS. 5. Through a combination of Pathway, miRNA-Gene-Network and miRNA-Go- Network analysis, 29 miRNA-mRNA-regulated pathways were identified such as miR-148a/TEK/PI3K-Akt signaling pathway, miR-195/BDNF/MAPK signaling pathway, miR-195/DLL1/Notch signaling pathway, miR-145/CCND2/ JAK-STAT signaling pathway, etc. (Table 1). Conclusion Alteration expression of several miRNAs and targeted mRNAs might have an important impact on cancer-related cellular pathways including MAPK, PI3K/Akt, JAK/STAT, etc. The role of these miRNAs-mediated pathways in pathogenesis of MDS merit further investigation. Fig. 1 Affymetrix mcroRNA and mRNA microarray in MDS Fig. 1. Affymetrix mcroRNA and mRNA microarray in MDS Fig. 2 Significant miRNA-mRNA pairs identified through a integration of mcroRNA-mRNA microarray Fig. 2. Significant miRNA-mRNA pairs identified through a integration of mcroRNA-mRNA microarray Table 1. Parts of dysregulated miRNAs, genes and targeted pathway in MDS MicroRNA Style Gene_synbol Pathway miR-148a Down TEK PI3K-Akt signaling pathway ITGA9 PI3K-Akt signaling pathway KIT PI3K-Akt signaling pathway HMGA2 Transcriptional misregulation in cancer miR-145 Down HHEX Transcriptional misregulation in cancer MEIS1 Transcriptional misregulation in cancer miR-200c Down EFNA1 PI3K-Akt signaling pathway KLF3 Transcriptional misregulation in cancer miR-195 Up BDNF MAPK signaling pathway CDC25B MAPK signaling pathway DLL1 Notch signaling pathway MRAS MAPK signaling pathway miR-17 Up CAMK2D Calcium signaling pathway miR-19a Up MAML1 Notch signaling pathway SLC8A1 Calcium signaling pathway THBS1 Proteoglycans in cancer TNF MAPK signaling pathway TNFRSF1B Adipocytokine signaling pathway ACSL1 Adipocytokine signaling pathway EDNRB Calcium signaling pathway miR-19b Up CALM1 Calcium signaling pathway TNF Proteoglycans in cancer Fig. 3 Go and pathway analysis Fig. 3. Go and pathway analysis Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  

Background. Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active components and mechanisms of ZJP are still arcane. This study aimed to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC. Methods. Firstly, the components and putative targets of ZJP were collected based on herbal medicine target databases, and a network containing the interaction between the targets of ZJP and the potential therapeutic targets of UC was established. Then, topological parameters were calculated to identify the key targets in the network and, in turn, to import them into the David database to perform path enrichment analysis. Results. 14 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, MAPK cascade, inflammatory response, immune response, and the apoptotic process of UC. Moreover, the PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor signaling pathway, and Prolactin signaling pathway were predicted to participate in ZJP treating UC. Among them, 14 active components of ZJP directly regulate these pathways. Conclusion. ZJP could alleviate UC through the predicted components and mechanisms. The 14 predicted active components of ZJP may mainly play a therapeutic role for UC through synergistic regulation of the PI3K-Akt signaling pathway and MAPK signaling pathway.


2021 ◽  
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  

Abstract Background: Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active component and mechanism of ZJP is still arcane. Objective: This study aims to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC.Methods: Firstly, the components and putative targets of ZJP were collected based on the herbal medicine target database, and a network containing the interaction between the putative targets of ZJP and the potential therapeutic targets of UC was established. Then topological parameters were calculated to identify the key targets in the network and the key targets were imported into David database to perform path enrichment analysis.Results: 7 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, response to drug, cellular response to lipopolysaccharide, MAPK cascade, inflammatory response, immune response, transcription from RNA polymerase II promoter, apoptotic process, regulation of sequence-specific DNA binding transcription factor activity and lipopolysaccharide-mediated signaling pathway. Moreover, PI3K-Akt signaling pathway, MAPK signaling pathway and Toll-like receptor signaling pathway were predicted to participate in the treatment of UC, which directly regulated by 7 active components of ZJP. Quercetin and isorhamnetin have great development value in the treatment of UC. Moupinamide and palmidin A are of great value for exploration because of their safety and innovation.Conclusion: ZJP mainly were directly involved in UC through inflammation and immune regulation by PI3K-Akt signaling pathway and MAPK signaling pathway.


2021 ◽  
Author(s):  
Huihui Gao ◽  
Heran Cao ◽  
Tianqi Jin ◽  
Guofan Peng ◽  
Yining Chen ◽  
...  

Abstract BackgroundSpermatogenesis is a highly complicated biological process that occurs in the epithelium of the seminiferous tubules. It is regulated by a complex network of endocrine and paracrine factors and juxtacrine testicular cross-talk . Sertoli cells (SCs) play a key role in spermatogenesis due to their production of trophic, differentiation and immune-modulating factors. However, many of the molecular pathways of SCs action remain controversial and unclear. Recently, research has focused on exosomes as an important mechanism of intercellular communication. ResultsW e found that the exosomes derived from SCs ( SC-Exos ) significantly inhibited the apoptosis of the primary spermatogonial stem cells (SSCs). Total of 1016 miRNAs in SCs and 556 miRNAs in SC-Exos were detected using microRNA (miRNA) high-throughput sequencing. Further, 294 miRNAs were differentially expressed between SCs and SC-Exos. Based on the GO and KEGG analyses, the target genes of 37 (high-expressed in exosomes and RPM>1000) selected miRNAs were involved in multiple biological pathw ays, including the MAPK signaling pathway and PI3K/AKT signaling pathway. And miR-10b is one of the top ten exosomes with relatively large enrichment of microRNA. In addition, the overexpression of miR-10b down-regulated expression of the target KLF4 to reduce spermatogonial apoptosis in SSCs or C18-4 cell line. ConclusionsThe study indicated a large number of small RNAs loaded in exosomes was secreted form the donor SCs to target spermatogonial regulated the apoptosis. And miR-10b inhibits the apoptosis of spermatogonia through the target gene KLF4.


2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Suhua Li ◽  
Xuan Huang ◽  
Shun Wang ◽  
Xueqian Chu ◽  
Munire Aierken

Background. Ischemia-reperfusion acute kidney injury (I/R AKI) is a severe kidney disease with high mortality and morbidity. This study aimed to explore the protective mechanism of glutamine (GLN) against I/R AKI. Methods.The I/R AKI rat model was established, and HE staining of kidney tissue and serum creatinine (SCr) and blood urea nitrogen (BUN) detection were performed. The miRNAs were sequenced by high throughput in rat kidney tissue samples. Differentially expressed miRNAs (DEmiRs) between the I/R group and I/R + GLN group were screened, and enrichment analysis for target genes of DEmiRs was performed. Meanwhile, human HK-2 cells were cultured, and an I/R model was established to verify the expression of DEmiRs. Results. Compared with the I/R group, the SCr and BUN levels at each time point were lower in the I/R + GLN group. Vacuolar degeneration of renal tubules in the I/R + GLN group was significantly reduced. In the 104 DEmiRs, we selected miR-132-5p, miR-205, and miR-615 as key miRNAs. KEGG analysis showed that the Notch signaling pathway, PI3K-Akt signaling pathway, and cGMP signaling pathway were mainly related to the GLN against I/R. qRT-PCR verified the downregulation of miR-205 in the I/R group, compared to the sham and I/R + GLN group. The I/R model was established with HK-2 cells, and the expression of miR-132-5p and miR-205 was decreased. Conclusion. GLN reduced I/R-induced AKI. There were significant differences between miRNAs expression in I/R after GLN treatment. The process of GLN against I/R-induced AKI may be related to the Notch and PI3K-Akt signaling pathway.


2020 ◽  
Author(s):  
Shengjue Xiao ◽  
Yufei Zhou ◽  
Qiaozhi Liu ◽  
Tiantian Zhang ◽  
Hong Zhu ◽  
...  

Abstract Background: Atrial fibrillation (AF) is the most common arrhythmia. However, specific molecular mechanism of AF remains unclear. Our study aimed to identify pivotal target genes and miRNAs in the process of AF, which help provide the basis for clinical diagnosis and the methods for early intervention. Methods: Three gene expression array datasets (GSE31821, GSE41177 and GSE79768) and a miRNA expression array dataset of AF dataset (GSE68475) were downloaded. Differential expressed genes (DEGs) were identified using the LIMMA package and differential expressed miRNAs (DEMs) were screened from GSE68475. Target genes of DEMs were predicted using the miRTarbase database, the number of the intersection between DEGs and these target genes was 26, named CDEGs. The common DEGs (CDEGs) was subject to following analysis. Results: A total of 264 DEGs and 40 DEMs were identified between the AF and control groups. Functional and pathway enrichment analyses of up-regulated DEGs and down-regulated DEGs were performed. The CDEGs were mainly enriched in PI3K-Akt signaling pathway, negative regulation of cell division and response to hypoxia. Subsequently, the protein-protein interaction (PPI) network, the microRNA‐transcription factor‐target regulatory network and drug‐gene network were also constructed by Cytoscape software. Conclusion: The present study revealed several novel genes and miRNAs involved in AF. We speculated that PI3K-Akt signaling pathway might participate in the pathogenesis of AF with the interaction of MYC proto-oncogene (MYC), heat shock protein 90 kDA alpha, class B, member 1 (HSP90AB1) and DNA damage-inducible transcript 4 (DDIT4), moreover, SOD2 (superoxide dismutase 2) could target miR-671-5p, miR-4306, miR-3125, miR-4298 in the progression of AF.


2021 ◽  
Author(s):  
Mingmin he ◽  
Xiongwei Cai ◽  
Yuanyuan Zeng

Abstract The purpose of this study was to investigate the relationship between RUNX1 mutations and MAPK signaling pathway in acute myeloid leukemia (AML). In this study, we analyzed miRNA expression with 5 mutant RUNX1 and 9 wild-type RUNX1 cases from TCGA database of AML. Six miRNAs were differently expressed with significance, and three of them were related to overall survival. Predicted target genes of these 3 miRNAs were highly enriched in MAPK signaling pathway by functional enrichment with miRWalk3.0. Besides, genes among RUNX1 associated genes directly regulated by RUNX1 were involved in MAPK signaling pathway, too. Taken together, we demonstrate three DEmiRNAs and three genes correlated to RUNX1 were correlated with prognosis in AML, and RUNX1 modulated MAPK signaling pathway in AML.


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