differentially expressed genes
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2022 ◽  
Vol 23 (2) ◽  
pp. 946
Christina J. Codden ◽  
Michael T. Chin

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy with or without left ventricular outflow tract (LVOT) obstruction. Single-nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples has revealed alterations in communication between various cell types, but no direct and integrated comparison between the two HCM phenotypes has been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility, and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding, and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication, and in endothelial cell communication to other cell types, largely through changes in the expression of integrin-β1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for the personalized management of different HCM phenotypes.

2022 ◽  
Paulina G. Eusebi ◽  
Natalia Sevane ◽  
Thomas O’Rourke ◽  
Manuel Pizarro ◽  
Cedric Boeckx ◽  

AbstractThe reactive type of aggression is regulated mostly by the brain’s prefrontal cortex; however, the molecular changes underlying aggressiveness in adults have not been fully characterized. We used an RNA-seq approach to investigate differential gene expression in the prefrontal cortex of bovines from the aggressive Lidia breed at different ages: young three-year old and adult four-year-old bulls. A total of 50 up and 193 down-regulated genes in the adult group were identified. Furthermore, a cross-species comparative analysis retrieved 29 genes in common with previous studies on aggressive behaviors, representing an above-chance overlap with the differentially expressed genes in adult bulls. We detected changes in the regulation of networks such as synaptogenesis, involved in maintenance and refinement of synapses, and the glutamate receptor pathway, which acts as excitatory driver in aggressive responses. The reduced reactive aggression typical of domestication has been proposed to form part of a retention of juvenile traits as adults (neoteny).

2022 ◽  
Vol 11 ◽  
Zhengqing Wan ◽  
Haofeng Xiong ◽  
Xian Tan ◽  
Tong Su ◽  
Kun Xia ◽  

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Due to the lack of early detection and treatment, the survival rate of OSCC remains poor and the incidence of OSCC has not decreased during the past decades. To explore potential biomarkers and therapeutic targets for OSCC, we analyzed differentially expressed genes (DEGs) associated with OSCC using RNA sequencing technology. Methylation−regulated and differentially expressed genes (MeDEGs) of OSCC were further identified via an integrative approach by examining publicly available methylomic datasets together with our transcriptomic data. Protein−protein interaction (PPI) networks of MeDEGs were constructed and highly connected hub MeDEGs were identified from these PPI networks. Subsequently, expression and survival analyses of hub genes were performed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) online tool. A total of 56 upregulated MeDEGs and 170 downregulated MeDEGs were identified in OSCC. Eleven hub genes with high degree of connectivity were picked out from the PPI networks constructed by those MeDEGs. Among them, the expression level of four hub genes (CTLA4, CDSN, ACTN2, and MYH11) were found to be significantly changed in the head and neck squamous carcinoma (HNSC) patients. Three hypomethylated hub genes (CTLA4, GPR29, and TNFSF11) and one hypermethylated hub gene (ISL1) were found to be significantly associated with overall survival (OS) of HNSC patients. Therefore, these hub genes may serve as potential DNA methylation biomarkers and therapeutic targets of OSCC.

2022 ◽  
pp. 1-12
Zhengfei Ma ◽  
Ping Zhong ◽  
Peidong Yue ◽  
Zhongwu Sun

<b><i>Background:</i></b> Intracranial aneurysm (IA) is a serious cerebrovascular disease. The identification of key regulatory genes can provide research directions for early diagnosis and treatment of IA. <b><i>Methods:</i></b> Initially, the miRNA and mRNA data were downloaded from the Gene Expression Omnibus database. Subsequently, the limma package in R was used to screen for differentially expressed genes. In order to investigate the function of the differentially expressed genes, a functional enrichment analysis was performed. Moreover, weighted gene co-expression network analysis (WGCNA) was performed to identify the hub module and hub miRNAs. The correlations between miRNAs and mRNAs were assessed by constructing miRNA-mRNA regulatory networks. In addition, in vitro validation was performed. Finally, diagnostic analysis and electronic expression verification were performed on the GSE122897 dataset. <b><i>Results:</i></b> In the present study, 955 differentially expressed mRNAs (DEmRNAs, 480 with increased and 475 with decreased expression) and 46 differentially expressed miRNAs (DEmiRNAs, 36 with increased and 10 with decreased expression) were identified. WGCNA demonstrated that the yellow module was the hub module. Moreover, 16 hub miRNAs were identified. A total of 1,124 negatively regulated miRNA-mRNA relationship pairs were identified. Functional analysis demonstrated that DEmRNAs in the targeted network were enriched in vascular smooth muscle contraction and focal adhesion pathways. In addition, the area under the curve of 16 hub miRNAs was &#x3e;0.8. It is implied that 16 hub miRNAs may be used as potential diagnostic biomarkers of IA. <b><i>Conclusion:</i></b> Hub miRNAs and key signaling pathways were identified by bioinformatics analysis. This evidence lays the foundation for understanding the underlying molecular mechanisms of IA and provided potential therapeutic targets for the treatment of this disease.

2022 ◽  
Vol 22 (1) ◽  
Bin Song ◽  
Hong Ge ◽  
Chenwei Pu ◽  
Ning Li

Abstract Background The resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs) therapy is currently the major clinical challenge in the treatment of lung cancer. This study aims to reveal the role of glucagon-like peptide (GLP) 2 and GLP-2 receptor (GLP2R) signaling on the EGFR-TKIs and cisplatin resistance of lung cancer cells. Methods The common differentially expressed genes in PC9 and HCC827 cells that were individually resistant to one of the three EGFR-TKIs (dacomitinib, osimertinib and afatinib) were screened. The data were from GSE168043 and GSE163913. The expression of GLP2R in drug-resistant cells was detected by western blot. The effect of GLP2R expression down- or up-regulation on resistance to dacomitinib, osimertinib, afatinib or cisplatin was measured by CCK-8 and flow cytometry assays. The long-acting analog of GLP-2, teduglutide, treated the parental cells. Results A total of 143 common differentially expressed genes were identified. Compared with the parent cells, the GLP2R expression in drug-resistant cell lines was significantly up-regulated. The exogenous expression of GLP2R in parental cells enhanced cell viability, while knockdown of GLP2R levels in drug-resistant cell lines inhibited cell viability. In addition, teduglutide treatment also enhanced the viability of lung cancer cells. Conclusion GLP2-GLP2R signal may change the sensitivity of cells to EGFR-TKIs and cisplatin. The development of GLP-2 or GLP2R inhibitors may be beneficial to the clinical treatment of lung cancer.

Shumei Zhang ◽  
Haoran Jiang ◽  
Bo Gao ◽  
Wen Yang ◽  
Guohua Wang

Background: Breast cancer is the second largest cancer in the world, the incidence of breast cancer continues to rise worldwide, and women’s health is seriously threatened. Therefore, it is very important to explore the characteristic changes of breast cancer from the gene level, including the screening of differentially expressed genes and the identification of diagnostic markers.Methods: The gene expression profiles of breast cancer were obtained from the TCGA database. The edgeR R software package was used to screen the differentially expressed genes between breast cancer patients and normal samples. The function and pathway enrichment analysis of these genes revealed significant enrichment of functions and pathways. Next, download these pathways from KEGG website, extract the gene interaction relations, construct the KEGG pathway gene interaction network. The potential diagnostic markers of breast cancer were obtained by combining the differentially expressed genes with the key genes in the network. Finally, these markers were used to construct the diagnostic prediction model of breast cancer, and the predictive ability of the model and the diagnostic ability of the markers were verified by internal and external data.Results: 1060 differentially expressed genes were identified between breast cancer patients and normal controls. Enrichment analysis revealed 28 significantly enriched pathways (p &lt; 0.05). They were downloaded from KEGG website, and the gene interaction relations were extracted to construct the gene interaction network of KEGG pathway, which contained 1277 nodes and 7345 edges. The key nodes with a degree greater than 30 were extracted from the network, containing 154 genes. These 154 key genes shared 23 genes with differentially expressed genes, which serve as potential diagnostic markers for breast cancer. The 23 genes were used as features to construct the SVM classification model, and the model had good predictive ability in both the training dataset and the validation dataset (AUC = 0.960 and 0.907, respectively).Conclusion: This study showed that the difference of gene expression level is important for the diagnosis of breast cancer, and identified 23 breast cancer diagnostic markers, which provides valuable information for clinical diagnosis and basic treatment experiments.

2022 ◽  
qiwei yang ◽  
wei yang ◽  
yijun tian ◽  
da xu ◽  
chuanmin chu ◽  

Abstract Backgrounds: The incidence of renal cancer is relatively insidious, and some patients have been metastatic renal cancer at the initial visit. Sunitinib is the first-line systemic therapy for patients with metastatic renal cell carcinoma, however, there is scant analysis of its effect on genes and microRNAs.Methods: In this study, 8 differentially expressed microRNAs and 112 differentially expressed genes were designated by analyzing mRNA and microRNA data sets and weighted correlation network analysis (WGCNA).Results: NIPSNAP1 gene showed the most co-expression with other genes. Through the intersection of the microRNA target gene with our differentially expressed genes, we got 26 genes. KEGG and GO analysis showed that these genes were predominantly concentrated in Pathways in cancer, Sphingolipid metabolism and Glycosaminoglycan degradation. After we set the 26 genes and gene of WGCNA do intersection, received six genes, respectively is NIPSNAP1, SDC4, TBC1D9, NEU1, STK40 and PLAUR. Conclusion: Through subsequent cell, molecular and flow cytometry experiments, we found the PLAUR would play a crucial role in renal cell carcinoma (RCC) resistant to sunitinib, which will be available for new ideas to forecast sunitinib resistance and reverse sunitinib resistance.

2022 ◽  
Vol 22 (1) ◽  
Lu-Lu Yu ◽  
Cui-Jiao Liu ◽  
Ye Peng ◽  
Zheng-Quan He ◽  
Fei Xu

Abstract Background Cyanide is a natural metabolite that exists widely in plants, and it is speculated to be involved in the regulation of various growth and development processes of plants in addition to being regarded as toxic waste. Previous studies have shown that exogenous cyanide treatment helps to improve seed germination, but the mechanism is still unclear. In this study, tomato (Solanum lycopersicum cv. Alisa Craig) was used as the material, and the effects of cyanide pretreatment at different concentrations on tomato seed germination were investigated. Results The results showed that exogenous application of a lower concentration of cyanide (10 μmol/L KCN) for 12 h strongly increased the tomato seed germination rate. RNA-Seq showed that compared with the control, a total of 15,418 differentially expressed genes (P<0.05) were obtained after pretreatment with KCN for 12 h, and in the next 12 h, a total of 13,425 differentially expressed genes (P<0.05) were regulated. GO and KEGG analyses demonstrated that exogenous KCN pretreatment was involved in regulating the expression (mainly downregulation) of seed storage proteins, thereby accelerating the degradation of stored proteins for seed germination. In addition, KCN pretreatment was also involved in stimulating glycolysis, the TCA cycle and oxidative phosphorylation. Notably, it is shown that KCN acted on the regulation of plant hormone biosynthesis and perception, i.e., down-regulated the gene expression of ABA biosynthesis and signal transduction, but up-regulated the expression of genes related to GA biosynthesis and response. Consistent with this, plant hormone measurements confirmed that the levels of ABA were reduced, but GA levels were induced after pretreatment with KCN. Conclusion These findings provide new insights into the regulation of seed germination by cyanide, that is cyanide-mediated seed germination occurs in a time- and dose-dependent manner, and is related to the mobilization of energy metabolism and the regulation of some plant hormone signals.

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Xiaofeng Li ◽  
Qiu Wang ◽  
Zhicheng Wu ◽  
Jiantong Zheng ◽  
Ling Ji

Background. One of the most usual gynecological state of tumor is ovarian cancer and is a major reason of gynecological tumor-related global mortality rate. There have been multiple risk elements related to ovarian cancer like the background of past cases associated with breast cancer or ovarian cancer, or excessive body weight issues, case history of smoking, and untimely menstruation or menopause. Because of unclear expressions, more than 70% of the ovarian cancer patient cases are determined during the early stage. Material and Methods. GSE38666, GSE40595, and GSE66957 were the three microarray datasets which were analyzed using GEO2R for screening the differentially expressed genes. GO, Kyoto Encyclopedia of Genes, and protein expression studies were performed for analysis of hub genes. Then, survival analysis was performed for all the hub genes. Results. From the dataset, a total of 199 differentially expressed genes (DEGs) were identified. Through the KEGG pathway study, it was noted that the DEGs are mainly linked with the AGE-RAGE signaling pathway, central carbon metabolism, and human papillomavirus infection. The survival analysis showed 4 highly expressed hub genes COL4A1, SDC1, CDKN2A, and TOP2A which correlated with overall survival in ovarian cancer patients. Moreover, the expression of the 4 hub genes was validated by the GEPIA database and the Human Protein Atlas. Conclusion. The results have shown that all 4 hub genes were found to be upregulated in ovarian cancer tissues which predict poor prognosis in patients with ovarian cancer.

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