scholarly journals Screening and identification of critical biomarkers in erectile dysfunction: evidence from bioinformatic analysis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8653 ◽  
Author(s):  
Jialiang Hui ◽  
Ruiyu Liu ◽  
Haibo Zhang ◽  
Shuhua He ◽  
Anyang Wei
Keyword(s):  
Erectile Dysfunction ◽  
Rna Polymerase Ii ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Protein Digestion ◽  
Akt Signaling Pathway ◽  
Hub Genes

Purpose Erectile dysfunction (ED) is one of the most common male-disease globally. Despite efforts to explain its pathogenesis, the molecular mechanisms of ED are still not well understood. Methods The microarray dataset GSE10804 was downloaded from the Gene Expression Omnibus (GEO) to find candidate genes in ED progression. After differentially expressed genes (DEGs) were identified, functional enrichment analysis was performed. In addition, a protein-protein interaction network (PPI) was established and module analysis was performed through the STRING and Cytoscape. Results and Conclusions A total of 618 DEGs were identified in all, containing 430 downregulated genes and 188 upregulated genes. The enriched functions and pathways of the DEGs include transcription from RNA polymerase II promoter, cell adhesion, calcium ion binding, receptor binding, Akt signaling pathway, receptor interaction, protein digestion, and absorption. We picked out twenty-five hub genes, with biological process (BP) analyses revealing that the genes were principally associated with cellular responses to amino acid stimuli, extracellular matrix structural constituent, collagen trimer, protein digestion and absorption, ECM-receptor interaction and PI3K-Akt signaling pathway. To sum up, DEGs and hub genes distinguished in this study not only help us understand the molecular mechanisms behind the carcinogenesis and progression of ED, but also play a part in the diagnosis and treatment of ED by providing candidate targets.

scholarly journals P4HA2 is associated with prognosis, promotes proliferation, invasion, migration and EMT in glioma

2020 ◽  
Author(s):  
Jing Lin ◽  
Xiao-Jun Wu ◽  
Wen-Xin Wei ◽  
Xing-Chun Gao ◽  
Ming-Zhu Jin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Tumor Xenograft ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

AbstractProlyl-4-hydroxylase subunit 2 (P4HA2), as a member of collagen modification enzymes, is induced under hypoxic conditions with essential roles in the collagen maturation, deposition as well as the remodeling of extracellular matrix(ECM). Mounting evidence has suggested that deregulation of P4HA2 is common in cancer. However, the expression pattern and molecular mechanisms of P4HA2 in glioma remain unknown. Here, we demonstrate that P4HA2 is overexpressed in glioma and inversely correlates with patient survival. Knockdown of P4HA2 inhibits proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT)-like phenotype of glioma cells in vitro and suppressed tumor xenograft growth in vivo. Mechanistically, bioinformatics analysis shows that ECM-receptor interaction and PI3K/AKT pathway are the most enriched pathways of the co-expressed genes with P4HA2. Furthermore, P4HA2 mRNA was positively correlated with mRNA expressions of a series of collagen genes, but not mRNA of PI3K or AKT1/2. Conversely, both the protein expressions of collagens and phosphorylated PI3K/AKT could be downregulated either by silencing of P4HA2 expression or inhibition of its prolyl hydroxylase. Moreover, the inhibitory effects on the migration, invasion and the EMT-related molecules by P4HA2 knockdown can be recapitulated by the Akt phosphorylation activator. Taken together, our findings for the first time reveal an oncogenic role of P4HA2 in the glioma malignancy. By regulating the expression of fibrillar collagens and the downstream PI3K/AKT signaling pathway, it may serve as a potential anti-cancer target for the treatment of glioma.HighlightsP4HA2 is overexpressed and correlated with poor prognosis in glioma.P4HA2 depletion inhibits glioma proliferation, migration, invasion and EMT-like phenotype in vitro and tumorigenesis in vivo.P4HA2 depletion attenuates the PI3K/AKT signaling pathway in a collagen-dependent manner.

scholarly journals Anticancer Effects of Emodin on HepG2 Cell: Evidence from Bioinformatic Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Rui-sheng Zhou ◽  
Xiong-Wen Wang ◽  
Qin-feng Sun ◽  
Zeng Jie Ye ◽  
Jian-wei Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Ion Concentration ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Mrna Levels ◽  
Hub Genes ◽  
Positive Regulation

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related death in the world. Despite the fact that there are many methods to treat HCC, the 5-year survival rate of HCC is still at a low level. Emodin can inhibit the growth of HCC cells invitroand invivo. However, the gene regulation of emodin in HCC has not been well studied. In our research, RNA sequencing technology was used to identify the differentially expressed genes (DEGs) in HepG2 cells induced by emodin. A total of 859 DEGs were identified, including 712 downregulated genes and 147 upregulated genes in HepG2 cells treated with emodin. We used DAVID for function and pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING, and Cytoscape was used for module analysis. The enriched functions and pathways of the DEGs include positive regulation of apoptotic process, structural molecule activity and lipopolysaccharide binding, protein digestion and absorption, ECM-receptor interaction, complement and coagulation cascades, and MAPK signaling pathway. 25 hub genes were identified and pathway analysis revealed that these genes were mainly enriched in neuropeptide signaling pathway, inflammatory response, and positive regulation of cytosolic calcium ion concentration. Survival analysis showed that LPAR6, C5, SSTR5, GPR68, and P2RY4 may be involved in the molecular mechanisms of emodin therapy for HCC. A quantitative real-time PCR (qRT-PCR) assay showed that the mRNA levels of LPAR6, C5, SSTR5, GPR68, and P2RY4 were significantly decreased in HepG2 cells treated with emodin. In conclusion, the identified DEGs and hub genes in the present study provide new clues for further researches on the molecular mechanisms of emodin.

scholarly journals TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

2021 ◽  
Vol 10 ◽  
Author(s):  
Mengya Zhong ◽  
Xingfeng Qiu ◽  
Yu Liu ◽  
Yan Yang ◽  
Lei Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hct116 Cells ◽  
Proliferation And Migration

Tumor necrosis factor-induced protein-8 (TIPE) is highly expressed in colorectal cancer (CRC). Decoy receptor 3 (DcR3) is a soluble secreted protein that can antagonize Fas ligand (FasL)-induced apoptosis and promote tumorigenesis. It remains unclear whether TIPE can regulate DcR3 expression. In this study, we examined this question by analyzing the relationship between these factors in CRC. Bioinformatics and tissue microarrays were used to determine the expression of TIPE and DcR3 and their correlation in CRC. The expression of TIPE and DcR3 in colon cancer cells was detected. Plasma samples were collected from CRC patients, and DcR3 secretion was measured. Then, dual-luciferase reporter gene analysis was performed to assess the interaction between TIPE and DcR3. We exogenously altered TIPE expression and analyzed its function and influence on DcR3 secretion. Lipopolysaccharide (LPS) was used to stimulate TIPE-overexpressing HCT116 cells, and alterations in signaling pathways were detected. Additionally, inhibitors were used to confirm molecular mechanisms. We found that TIPE and DcR3 were highly expressed in CRC patients and that their expression levels were positively correlated. DcR3 was highly expressed in the plasma of cancer patients. We confirmed that TIPE and DcR3 were highly expressed in HCT116 cells. TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter. TIPE activated the PI3K/AKT signaling pathway to regulate the expression of DcR3, thereby promoting cell proliferation and migration and inhibiting apoptosis. In summary, TIPE and DcR3 are highly expressed in CRC, and both proteins are associated with poor prognosis. TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC, thus promoting cell proliferation and migration and inhibiting apoptosis. These findings may have clinical significance and promise for applications in the treatment or prognostication of CRC.

scholarly journals Identification of biomarkers associated with ovarian cancer based on transcriptome sequencing

2019 ◽  
Author(s):  
jiazhou chen ◽  
xiandong peng ◽  
min yu
Keyword(s):  
Ovarian Cancer ◽  
Cell Adhesion ◽  
Western Blot ◽  
Signaling Pathway ◽  
Transcriptome Sequencing ◽  
Akt Signaling ◽  
Serous Carcinoma ◽  
Receptor Interaction ◽  
List Type ◽  
Akt Signaling Pathway

AbstractObjectiveThis study aimed to explore more biomarkers associated with ovarian cancer.MethodsCell lines SKOV-3 (ovarian serous carcinoma cells) and MCV152 (benign ovarian epithelial tumor cell) were used in this study and performed transcriptome sequencing. The differentially expressed genes (DEGs) between ovarian cancer cells (SKOV-3) and controls (MCV152) were identified, followed by function enrichment analysis. The expression levels of genes involved in the key pathway were validated through PCR and western blot analyses.ResultsTotal 2,020 upregulated and 1,673 downregulated DEGs were obtained between SKOV3 and MCV152 cells. The upregulated and downregulated DEGs were significantly associated with cell adhesion. In addition, the upregulated DEGs were significantly involved in pathways of ECM-receptor interaction, and the downregulated DEGs were involved in PI3K-Akt signaling pathway. PCR and western blot analyses showed that genes (proteins) expression related to PI3K-Akt signaling pathway were in consistent with bioinformatics analysis.ConclusionCell adhesion and extracellular matrix (ECM)-receptor interaction may play an important role in the invasion of ovarian cancer. PI3K-Akt signaling pathway may be involved in the progression of ovarian cancer by up-regulating ANGPT2, FGF18, ITGB4 and ITGB8, and downregulating AKT3 and PIK3AP1.HighlightsCell adhesion and ECM-receptor interaction may play important roles in ovarian cancer invasion.PI3K-Akt signaling pathway may involve in ovarian cancer progression.ANGPT2, FGF18, ITGB4, ITGB8, AKT3 and PIK3AP1 may serve as biomarkers in ovarian cancer.

scholarly journals Midkine promotes glioblastoma progression via PI3K-Akt signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Beiquan Hu ◽  
Chao Qin ◽  
Li Li ◽  
Lei Wei ◽  
Xianlun Mo ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Lines ◽  
Regulatory Network ◽  
Poor Prognosis ◽  
Transcriptional Regulatory Network ◽  
Akt Signaling ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Aberrant Expression

Abstract Background Our previous bioinformatics-based study found that midkine (MDK) was associated with poor prognosis of glioblastoma (GBM). However, the mechanism of MDK in GBM remains elusive. Methods A public GBM-related dataset and GBM tissues from our center were used validate the aberrant expression of MDK in GBM at the RNA and protein levels. The relationship between MDK expression and survival of GBM patients was also explored through survival analysis. Subsequently, we identified MDK-related GBM-specific genes using differential expression analysis. Functional enrichment analyses were performed to reveal their potential biological functions. CCK-8, 5-ethynyl-2′-deoxyuridine, and Matrigel-transwell assays were performed in GBM cell lines in which MDK was knocked out or overexpressed in order assess the effects of MDK on proliferation, migration, and invasion of GBM cells. Western blotting was performed to detect candidate proteins. Results Our study showed MDK is a promising diagnostic and prognostic biomarker for GBM because it is highly expressed in the disease and it is associated with poor prognosis. MDK is involved in various cancer-related pathways, such as PI3K-Akt signaling, the cell cycle, and VEGF signaling. A comprehensive transcriptional regulatory network was constructed to show the potential pathways through which MDK may be involved in GBM. In vitro, Overexpression of MDK augmented proliferation, migration, and invasion of GBM cell lines, whereas suppression of MDK led to the opposite effects. Furthermore, our study confirmed that MDK promotes the progression of GBM by activating the PI3K-Akt signaling pathway. Conclusions Our present study proposes that MDK promotes GBM by activating the PI3K-Akt signaling pathway, and it describes a potential regulatory network involved.

scholarly journals Identifying hub genes associated with clinical characteristicsin IgA nephropathy by Weighted Gene Co-expression Network Analysis

2019 ◽  
Author(s):  
Chengyu Yang ◽  
Chenyu Li ◽  
Long Zhao ◽  
Bin Zhou ◽  
Xiaofei Man ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Signaling Pathway ◽  
Clinical Characteristics ◽  
Enrichment Analysis ◽  
Akt Signaling ◽  
Differentially Expressed ◽  
Akt Signaling Pathway ◽  
Hub Genes ◽  
Renal Interstitium ◽  
Healthy Control

Abstract Background: Clinically, IgA nephropathy has a variety of symptoms including paroxysmal gross hematuria, nephritic and nephrotic syndrome. This study aimed at investigating hub geneand genes modular related to IgA nephropathy clinical characteristics by using weighted gene co-expression network analysis combining clinical, microarray and network database parameters. Methods: We collected 32 human samples from the European Renal cDNA Bank and used RMA method to preprocess the data and utilize the limma package to obtain differentially expressed gene in renal interstitium and glomeruli. We used the WGCNA package to construct the gene co-expression of differential expression genes and identify hub genes associated with clinical characteristics in renal interstitium and glomeruli, respectively. Gene ontology enrichment analysis and KEGG analysis for hub genes which associated with clinical characteristics were performed by DAVID. PPI information was acquired from STRING. Results: For glomeruli, 1470 genes differentially expressed between IgA nephropathy patients and healthy control, containing 10 hub genes associated with age, 8 hub genes associated with sex, 48 hub genes associated with Bp enrichd in ERK1 and ERK2 cascade and Rap1 signaling pathway, 223 hub genes associated with BMI enrich in organic acid catabolic process and fatty acid degradation pathway, 136 hub genes associated GFR enriched in immune response and PI3K-Akt signaling pathway, 82 hub genes associated with proteinuria enriched in extracellular matrix organization and PI3K-Akt signaling pathway. In tubulointerstitium, there were 480 genes differentially expressed between IgA nephropathy patients and healthy control. Among 480 DEGs, 6 hub genes associated with age, 15 hub genes associated with sex, 35 hub genes associated with Bp enrichd in positive regulation of apoptotic process, 87 hub genes associated with GFR enriched in negative regulation of macromolecule metabolic process and RNA transport, 33 hub genes associated with proteinuria enriched in regulation of apoptotic process and FoxO signaling pathway. PPI enrichment analysis shown that all hub genes sets are biologically connected cluster. Conclusions: We made a preliminary investigation on molecular mechanisms of relationship between IgA nephropathy and clinical characteristics and identified hub genes and pathways closely related with BMI, GFR and Proteinuria in IgA nephropathy by a series of bioinformatics analysis.

scholarly journals Bcl-2 Is Involved in Cardiac Hypertrophy through PI3K-Akt Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xianwei Meng ◽  
Jun Cui ◽  
Guibin He
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
B Cell Lymphoma ◽  
Akt Signaling ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Akt Signaling Pathway ◽  
Upregulated Genes

Cardiac hypertrophy (CH) is a common cause of sudden cardiac death and heart failure, resulting in a significant medical burden. The present study is aimed at exploring potential CH-related pathways and the key downstream effectors. The gene expression profile of GSE129090 was obtained from the Gene Expression Omnibus database (GEO), and 1325 differentially expressed genes (DEGs) were identified, including 785 upregulated genes and 540 downregulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway enrichment analysis of DEGs were then performed. Although there were no pathways enriched by downregulated genes, many CH-related pathways were identified by upregulated genes, including PI3K-Akt signaling pathway, extracellular matrix- (ECM-) receptor interaction, regulation of actin cytoskeleton, and hypertrophic cardiomyopathy (HCM). In the deeper analysis of PI3K-Akt signaling pathway, we found all the signaling transduction pointed to B cell lymphoma-2- (Bcl-2-) mediated cell survival. We then demonstrated that PI3K-Akt signaling pathway was indeed activated in cardiac hypertrophy. Furthermore, no matter LY294002, an inhibitor of the PI3K/AKT signaling pathway, or Venetoclax, a selective Bcl-2 inhibitor, protected against cardiac hypertrophy. In conclusion, these data indicate that Bcl-2 is involved in cardiac hypertrophy as a key downstream effector of PI3K-Akt signaling pathway, suggesting a potential therapeutic target for the clinical management of cardiac hypertrophy.

scholarly journals Compound K Inhibits Autophagy-Mediated Apoptosis Through Activation of the PI3K-Akt Signaling Pathway Thus Protecting Against Ischemia/Reperfusion Injury

2018 ◽  
Vol 47 (6) ◽  
pp. 2589-2601 ◽  
Author(s):  
Xiangyan Li ◽  
Qingxia Huang ◽  
Manying Wang ◽  
Xiuci Yan ◽  
Xinying Song ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Mitochondrial Damage ◽  
Tunel Staining ◽  
Ros Generation ◽  
Akt Signaling Pathway ◽  
Compound K

Background/Aims: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. Methods: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. Results: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. Conclusions: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury.

scholarly journals Hyperoside Protects Against Pressure Overload-Induced Cardiac Remodeling via the AKT Signaling Pathway

2018 ◽  
Vol 51 (2) ◽  
pp. 827-841 ◽  
Author(s):  
Xiaofang Wang ◽  
Yuan Liu ◽  
Lili Xiao ◽  
Ling Li ◽  
Xiaoyan Zhao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Neonatal Rat ◽  
Control Group ◽  
Akt Signaling Pathway

Background/Aims: Cardiac hypertrophy is a major predisposing factor for heart failure and sudden cardiac death. Hyperoside (Hyp), a flavonoid isolated from Rhododendron ponticum L., is a primary component of Chinese traditional patent medicines. Numerous studies have shown that Hyp exerts marked anti-viral, anti-inflammatory, anti-oxidant, anti-cancer, anti-ischemic, and particularly cardio-protective effects. However, the effects of Hyp on cardiac hypertrophy have not been explored. The aims of this study were to determine whether Hyp could protect against cardiac remodeling and to clarify the potential molecular mechanisms. Methods: Neonatal rat cardiac myocytes were isolated and treated with different concentrations of Hyp, then cultured with angiotensin II for 48 h. Mice were subjected to either aortic banding or sham surgery (control group). One week after surgery, the mice were treated with Hyp (20 mg/kg/day) or vehicle by oral gavage for 7 weeks. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histology, and biomarkers. Results: Hyp pretreatment suppressed angiotensin II-induced hypertrophy in cardiomyocytes. Hyp exerted no basal effects but attenuated cardiac hypertrophy and dysfunction, fibrosis, inflammation, and oxidative stress induced by pressure overload. Both in vivo and in vitro experiments demonstrated that the effect of Hyp on cardiac hypertrophy was mediated by blocking activation of the AKT signaling pathway. Conclusion: Hyp improves cardiac function and prevents the development of cardiac hypertrophy via AKT signaling. Our results suggest a protective effect of Hyp on pressure overload-induced cardiac remodeling. Taken together, Hyp may have a role in the pharmacological therapy of cardiac hypertrophy.

scholarly journals PTEN Plays an Important Role in Thrombin-Mediated Lung Cancer Cell Functions

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zhishan Xu ◽  
Lingyun Zhu ◽  
Min Yao ◽  
Genshen Zhong ◽  
Qiaoyan Dong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Akt Signaling ◽  
Pten Expression ◽  
Receptor Interaction ◽  
Akt Signaling Pathway ◽  
Lung Cancer Cell ◽  
Cell Growth And Migration ◽  
Cell Functions

Thrombin and its membrane receptor, protease-activated receptor 1 (PAR1), have been reported to promote the development of lung cancerin vitroandin vivo. However, the intracellular molecular mechanism or signaling pathway that mediates the cytological effects after the thrombin-receptor interaction is poorly understood. Our previous study observed that the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was downregulated in thrombin-stimulated lung cancer. In this study, the role of PTEN in thrombin-mediated cell function and the corresponding cell signaling pathway were studied in lung cancer cell Glc-82. The results indicated that thrombin downregulates the PTEN expression level and that PTEN plays an important role in thrombin-mediated Glc-82 functions, including cell cycle progression, cell apoptosis, and cell migration. The PI3K/AKT signaling pathway and its related proteins, including p27 and S phase kinase associated protein 2 (Skp2), are involved in the effects induced by PTEN downregulation. PAR1 plays a role in thrombin-mediated reduction of PTEN expression. This study suggested that the PTEN/PI3K/AKT signaling pathway plays an important role in thrombin/PAR1-mediated lung cancer cell growth and migration.

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