Bioinformatics Analysis of Key micro-RNAs and mRNAs under the Hand,Foot, and Mouth Disease Virus Infection

To clarify crucial key micro-RNAs and mRNAs associated with hand, foot, and mouth disease (HFMD) virus infection, we conducted this bioinformatics analysis from four GEO datasets. The following datasets were used for the analysis: {"type":"entrez-geo","attrs":{"text":"GSE85829","term_id":"85829"}}GSE85829, {"type":"entrez-geo","attrs":{"text":"GSE94551","term_id":"94551"}}GSE94551, {"type":"entrez-geo","attrs":{"text":"GSE52780","term_id":"52780"}}GSE52780, and {"type":"entrez-geo","attrs":{"text":"GSE45589","term_id":"45589"}}GSE45589. Differentially expressed genes (DEGs) were acquired, and the analysis of functional and pathway enrichment and the relative regulatory network were conducted. After screening common differentially expressed miRNAs (DE-miRNAs), five key miRNAs were acquired: miR-100-3p, miR-125a-3p, miR-1273g-3p, miR-5585-3p, and miR-671-5p. There were three common enriched GO terms between miRNA-derived prediction and mRNA-derived analysis: biosynthetic process, cytosol, and nucleoplasm. There was one common KEGG pathway, i.e., cell cycle shared between miRNA-based and mRNA-based enrichment. Using TarBase V8 in DIANA tools, we acquired 1,520 potential targets (mRNA) from the five key DE-miRNAs, among which the159 DE-mRNAs also included 11 DEGs. These common DEGs showed a PPI network mainly connected by SMC1A, SMARCC1, SF3B3, LIG1, and BRMS1L. Together, changes in five key miRNAs and 11 key mRNAs may play crucial roles in HFMD progression. A combination of these roles may benefit the early diagnosis and treatment of HFMD.Key words: HFMD, micro-RNA, protein-protein interaction, microarray, regulatory network     

Epigenetic alternations of microRNAs and DNA methylation contribute to gestational diabetes mellitus

This study aimed to identify epigenetic alternations of microRNAs and DNA methylation for gestational diabetes mellitus (GDM) diagnosis and treatment using in silico approach. Data of mRNA and miRNA expression microarray ({"type":"entrez-geo","attrs":{"text":"GSE103552","term_id":"103552"}}GSE103552 and {"type":"entrez-geo","attrs":{"text":"GSE104297","term_id":"104297"}}GSE104297) and DNA methylation data set ({"type":"entrez-geo","attrs":{"text":"GSE106099","term_id":"106099"}}GSE106099) were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated genes (DMGs) were obtained by limma package. Functional and enrichment analyses were performed with the DAVID database. The protein‐protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. Simultaneously, a connectivity map (CMap) analysis was performed to screen potential therapeutic agents for GDM. In GDM, 184 low miRNA‐targeting up‐regulated genes and 234 high miRNA‐targeting down‐regulated genes as well as 364 hypomethylation–high‐expressed genes and 541 hypermethylation–low‐expressed genes were obtained. They were mainly enriched in terms of axon guidance, purine metabolism, focal adhesion and proteasome, respectively. In addition, 115 genes (67 up‐regulated and 48 down‐regulated) were regulated by both aberrant alternations of miRNAs and DNA methylation. Ten chemicals were identified as putative therapeutic agents for GDM and four hub genes (IGF1R, ATG7, DICER1 and RANBP2) were found in PPI and may be associated with GDM. Overall, this study identified a series of differentially expressed genes that are associated with epigenetic alternations of miRNA and DNA methylation in GDM. Ten chemicals and four hub genes may be further explored as potential drugs and targets for GDM diagnosis and treatment, respectively.     

Bioinformatic analysis of key pathways and genes involved in pediatric atopic dermatitis

The initiation of atopic dermatitis (AD) typically happens very early in life, but most of our understanding of AD is derived from studies on AD patients in adult. The aim of the present study was to identify gene signature speficic to pediatric AD comapred with adult AD. The gene expression profiles of four datasets ({"type":"entrez-geo","attrs":{"text":"GSE32924","term_id":"32924"}}GSE32924, {"type":"entrez-geo","attrs":{"text":"GSE36842","term_id":"36842"}}GSE36842, {"type":"entrez-geo","attrs":{"text":"GSE58558","term_id":"58558"}}GSE58558, and {"type":"entrez-geo","attrs":{"text":"GSE107361","term_id":"107361"}}GSE107361) were downloaded from the GEO database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein–protein interaction (PPI) network was constructed by Cytoscape software. Total 654 differentially expressed genes (DEGs) (394 up-regulated and 260 down-regulated) were identified in pediatric AD samples with adult AD samples as control. The up-regulated DEGs were significantly enriched in the migration and chemotaxis of granulocyte and neutrophil, while down-regulated DEGs were significantly enriched in biological adhesion. KEGG pathway analysis showed that up-regulated DEGs participated in chemokine signaling pathway while down-regulated DEGs participated in adherens junction, focal adhesion, and regulation of actin cytoskeleton. The top 10 hub genes GAPDH, EGFR, ACTB, ESR1, CDK1, CXCL8, CD44, KRAS, PTGS2, and SMC3 were involved in chemokine signaling pathway, cytokine–cytokine receptor interaction, interleukin-17 signaling pathway, and regulation of actin cytoskeleton. In conclusion, we identified DEGs and hub genes involved in pediatric AD, which might be used as therapeutic targets and diagnostic biomarkers for pediatric AD.     

Mining the key genes for ventilator-induced lung injury using co-expression network analysis

Mechanical ventilation is extensively adopted in general anesthesia and respiratory failure management, but it can also induce ventilator-induced lung injury (VILI). Therefore, it is of great urgency to explore the mechanisms involved in the VILI pathogenesis, which might contribute to its future prevention and treatment. Four microarray datasets from the GEO database were selected in our investigation, and were subjected to the Weighted Gene Co-Expression Network Analysis (WGCNA) to identify the VILI-correlated gene modules. The limma package in R software was used to identify the differentially expressed genes (DEGs) between the VILI and control groups. WGCNA was constructed by merging the {"type":"entrez-geo","attrs":{"text":"GSE9314","term_id":"9314"}}GSE9314, {"type":"entrez-geo","attrs":{"text":"GSE9368","term_id":"9368"}}GSE9368, {"type":"entrez-geo","attrs":{"text":"GSE11434","term_id":"11434"}}GSE11434 and {"type":"entrez-geo","attrs":{"text":"GSE11662","term_id":"11662"}}GSE11662 datasets. A total of 49 co-expression network modules were determined as associated with VILI. The intersected genes between hub genes screened from DEGs for VILI and those identified using WGCNA were as follows: Tlr2, Hmox1, Serpine1, Mmp9, Il6, Il1b, Ptgs2, Fos and Atf3, which were determined to be key genes for VILI. Those key genes were validated by {"type":"entrez-geo","attrs":{"text":"GSE86229","term_id":"86229"}}GSE86229 and quantitative PCR (qPCR) experiment to have significantly statistical difference in their expression between the VILI and control groups. In a nutshell, nine key genes with expression differences in VILI were screened by WGCNA by integrating multiple datasets.     

Screening and identification of LMNB1 and DLGAP5, two key biomarkers in gliomas

Glioma is the most common primary cancer in the central nervous system. Despite advances in surgery, radiotherapy and chemotherapy over the past decades, the prognosis of glioblastoma patients remains poor. We aim to identify robust gene signatures to better understand the complex molecular mechanisms and to discover potential novel molecular biomarkers for glioma. By exploring {"type":"entrez-geo","attrs":{"text":"GSE16011","term_id":"16011"}}GSE16011, {"type":"entrez-geo","attrs":{"text":"GSE4290","term_id":"4290"}}GSE4290 and {"type":"entrez-geo","attrs":{"text":"GSE50161","term_id":"50161"}}GSE50161 data in Gene Expression Omnibus (GEO) database, we screened out 380 differentially expressed genes between non-tumor and glioma tissues, and further selected 30 hub genes through the Molecular Complex Detection (MCODE) plug-in in Cytoscape. In addition, LMNB1 and DLGAP5 were selected for further analyses due to their high expression in gliomas and were verified by using our cohort. Our study confirmed that LMNB1 and DLGAP5 were up-regulated in gliomas, and patients with high expression of LMNB1 or DLGAP5 had poor survival rate. Furthermore, silence of LMNB1 and DLGAP5 inhibited the proliferation of glioma cells. Together, LMNB1 and DLGAP5 were two potentially novel molecular biomarkers for diagnosis and prognosis of glioma.     

Identification of novel biomarkers and candidate small molecule drugs in rheumatoid arthritis and osteoarthritis based on bioinformatics analysis of high‐throughput data

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases. The present study aimed to identify hub genes involved in the pathogenesis and further explore the potential treatment targets of RA and OA.Methods: The gene expression profile of {"type":"entrez-geo","attrs":{"text":"GSE12021","term_id":"12021"}}GSE12021 was downloaded from Gene Expression Omnibus (GEO). Total 31 samples (12 RA, 10 OA and 9 NC samples) were used. The differentially expressed genes (DEGs) in RA versus NC, OA versus NC and RA versus OA groups were screened using limma package. We also verified the DEGs in {"type":"entrez-geo","attrs":{"text":"GSE55235","term_id":"55235"}}GSE55235 and {"type":"entrez-geo","attrs":{"text":"GSE100786","term_id":"100786"}}GSE100786. Functional annotation and protein–protein interaction (PPI) network construction of OA‐ and RA‐specific DEGs were performed. Finally, the candidate small molecules as potential drugs to treat RA and OA were predicted in CMap database.Results: 165 up-regulated and 163 down-regulated DEGs between RA and NC samples, 73 up-regulated and 293 down-regulated DEGs between OA and NC samples, 92 up-regulated and 98 down-regulated DEGs between RA and OA samples were identified. Immune response and TNF signaling pathway were significantly enriched pathways for RA‐ and OA‐specific DEGs, respectively. The hub genes were mainly associated with ‘Primary immunodeficiency’ (RA vs. NC group), ‘Ribosome’ (OA vs. NC group), and ‘Chemokine signaling pathway’ (RA vs. OA group). Arecoline and Cefamandole were the most promising small molecule to reverse the RA and OA gene expression.Conclusion: Our findings suggest new insights into the underlying pathogenesis of RA and OA, which may improve the diagnosis and treatment of these intractable chronic diseases.     

Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer

Background: The present study aimed to use bioinformatics tools to explore pivotal genes associated with the occurrence of gastric cancer (GC) and assess their prognostic significance, and link with clinicopathological parameters. We also investigated the predictive role of COL1A1, THBS2, and SPP1 in immunotherapy.Materials and methods: We identified differential genes (DEGs) that were up- and down-regulated in the three datasets ({"type":"entrez-geo","attrs":{"text":"GSE26942","term_id":"26942"}}GSE26942, {"type":"entrez-geo","attrs":{"text":"GSE13911","term_id":"13911"}}GSE13911, and {"type":"entrez-geo","attrs":{"text":"GSE118916","term_id":"118916"}}GSE118916) and created protein–protein interaction (PPI) networks from the overlapping DEGs. We then investigated the potential functions of the hub genes in cancer prognosis using PPI networks, and explored the influence of such genes in the immune environment.Results: Overall, 268 overlapping DEGs were identified, of which 230 were up-regulated and 38 were down-regulated. CytoHubba selected the top ten hub genes, which included SPP1, TIMP1, SERPINE1, MMP3, COL1A1, BGN, THBS2, CDH2, CXCL8, and THY1. With the exception of SPP1, survival analysis using the Kaplan–Meier database showed that the levels of expression of these genes were associated with overall survival. Genes in the most dominant module explored by MCODE, COL1A1, THBS2, and SPP1, were primarily enriched for two KEGG pathways. Further analysis showed that all three genes could influence clinicopathological parameters and immune microenvironment, and there was a significant correlation between COL1A1, THBS2, SPP1, and PD-L1 expression, thus indicating a potential predictive role for GC response to immunotherapy.Conclusion: ECM–receptor interactions and focal adhesion pathways are of great significance in the progression of GC. COL1A1, THBS2, and SPP1 may help predict immunotherapy response in GC patients.     

An autophagy-related prognostic signature associated with immune microenvironment features of uveal melanoma

Autophagy is involved in cancer initiation and progression but its role in uveal melanoma (UM) was rarely investigated. Herein, we built an autophagy-related gene (ARG) risk model of UM patients by univariate Cox regression and least absolute shrinkage and selection operator (Lasso) regression model and filtrated out nine prognostic ARGs in The Cancer Genome Atlas (TCGA) cohort. Survival and Receiver Operating Characteristic (ROC) Curve analysis in the TCGA and other four independent UM cohorts ({"type":"entrez-geo","attrs":{"text":"GSE22138","term_id":"22138"}}GSE22138, {"type":"entrez-geo","attrs":{"text":"GSE27831","term_id":"27831"}}GSE27831, {"type":"entrez-geo","attrs":{"text":"GSE44295","term_id":"44295"}}GSE44295 and {"type":"entrez-geo","attrs":{"text":"GSE84976","term_id":"84976"}}GSE84976) proved that the ARG-signature possessed robust and steady prognosis predictive ability. We calculated risk scores for patients included in our study and patients with higher risk scores showed worse clinical outcomes. We found the expressions of the nine ARGs were significantly associated with clinical and molecular features (including risk score) and overall survival (OS) of UM patients. Furthermore, we utilized univariate and multivariate Cox regression analyses to determine the independent prognostic ability of the ARG-signature. Functional enrichment analysis showed the ARG-signature was correlated with several immune-related processes and pathways like T-cell activation and T-cell receptor signaling pathway. Gene set enrichment analysis (GSEA) found tumor hallmarks including angiogenesis, IL6-JAK-STAT3-signaling, reactive oxygen species pathway and oxidative phosphorylation were enriched in high-risk UM patients. Finally, infiltrations of several immune cells and immune-related scores were found significantly associated with the ARG-signature. In conclusion, the ARG-signature might be a strong predictor for evaluating the prognosis and immune infiltration of UM patients.     

The diagnostic and prognostic values of microRNA-196a in cancer

MicroRNA-196a (miR-196a) was previously reported to be up-regulated in cancers, and it has the diagnostic and prognostic values in cancers. Whereas, the conclusion was still unclear according to the published data. To assess such roles of miR-196a in cancers, the present study was conducted based on published data and online cancer-related databases. To identify the relevant published data, we searched articles in databases and then the relevant data were extracted to evaluate the correlation between miR-196a expression and diagnosis, prognosis for cancer patients. The pooled results showed that miR-196a was a valuable diagnostic biomarker in cancer (area under curve (AUC) = 0.87, 95% CI: 0.84–0.90; sensitivity (SEN) = 0.73, 95% CI: 0.64–0.81; specificity (SPE) = 0.90, 95% CI: 0.81–0.95), which was consistent with the data from databases (breast cancer: miR-196a-3p: AUC = 0.77, 95% CI: 0.74–0.79; miR-196a-5p: AUC = 0.71, 95% CI: 0.66–0.75; pancreatic cancer: miR-196a-3p: AUC = 0.80, 95% CI: 0.73–0.87; miR-196a-5p: AUC = 0.61, 95% CI: 0.51–0.71). In addition, the pooled result revealed that elevated miR-196a expression in tumor tissues (HR = 2.54, 95% CI: 1.79–3.61, P_{Heterogeneity}=0.000, I² = 75.8%) or serum/plasma (HR = 4.06, 95% CI: 2.67–6.18, P_{Heterogeneity}=0.668, I² = 0%) of patients was an unfavorable survival biomarker, which was consistent with the data from databases (adrenocortical carcinoma: HR = 5.70; esophageal carcinoma: HR = 1.93; brain lower grade glioma: HR = 2.91; {"type":"entrez-geo","attrs":{"text":"GSE40267","term_id":"40267"}}GSE40267: HR = 2.47, 95% CI: 1.2–5.07; TCGA: HR = 1.82, 95% CI: 1.21–2.74; {"type":"entrez-geo","attrs":{"text":"GSE19783","term_id":"19783"}}GSE19783: HR = 4.24, 95% CI: 1–18.06). In short, our results demonstrated that miR-196a in tumor tissue or serum/plasma could be used as a prognostic and diagnostic values for cancers.     

Circulating lncRNA UCA1 and lncRNA PGM5-AS1 act as potential diagnostic biomarkers for early-stage colorectal cancer

Background: Colorectal cancer (CRC) is one of the most common and significant malignant diseases worldwide. In the present study, we evaluated two long non-coding RNAs (lncRNAs) in CRC patients as diagnostic markers for early-stage CRC.Methods: Using Gene Expression Omnibus (GEO) datasets {"type":"entrez-geo","attrs":{"text":"GSE102340","term_id":"102340"}}GSE102340, {"type":"entrez-geo","attrs":{"text":"GSE126092","term_id":"126092"}}GSE126092, {"type":"entrez-geo","attrs":{"text":"GSE109454","term_id":"109454"}}GSE109454 and {"type":"entrez-geo","attrs":{"text":"GSE115856","term_id":"115856"}}GSE115856, 14 differentially expressed lncRNAs were identified between cancer and adjacent tissues, among which, the two most differentially expressed were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR) in 200 healthy controls and 188 CRC patients. A receiver operating characteristic (ROC) analysis was employed to evaluate the diagnostic accuracy for CRC.Results: From four GEO datasets, three up-regulated and eleven down-regulated lncRNAs were identified in CRC tissues, among which, lncRNA urothelial carcinoma-associated 1 (UCA1) and lncRNA phosphoglucomutase 5-antisense RNA 1 (PGM5-AS1) were the most significantly up- and down-regulated lncRNAs in CRC patient plasma, respectively. The area under the ROC curve was calculated to be 0.766, 0.754 and 0.798 for UCA1, PGM5-AS1 and the combination of these two lncRNAs, respectively. Moreover, the diagnostic potential of these two lncRNAs was even higher for the early stages of CRC. The combination of UCA1 and PGM5-AS1 enhanced the AUC to 0.832, and when the lncRNAs were used with carcinoembryonic antigen (CEA), the AUC was further improved to 0.874.Conclusion: In the present study, we identified two lncRNAs, UCA1 and PGM5-AS1, in CRC patients’ plasma, which have the potential to be used as diagnostic biomarkers of CRC.     

FRZB as a key molecule in abdominal aortic aneurysm progression affecting vascular integrity

Abdominal aortic aneurysm (AAA), when ruptured, results in high mortality. The identification of molecular pathways involved in AAA progression is required to improve AAA prognosis. The aim of the present study was to assess the key genes for the progression of AAA and their functional role. Genomic and clinical data of three independent cohorts were downloaded from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) ({"type":"entrez-geo","attrs":{"text":"GSE57691","term_id":"57691"}}GSE57691, {"type":"entrez-geo","attrs":{"text":"GSE7084","term_id":"7084"}}GSE7084, and {"type":"entrez-geo","attrs":{"text":"GSE98278","term_id":"98278"}}GSE98278). To develop AAA diagnosis and progression-related differentially expressed genes (DEGs), we used a significance analysis of microarray (SAM). Spearman correlation test and gene set analysis were performed to identify potential enriched pathways for DEGs. Only the Frizzled-related protein (FRZB) gene and chromosome 1 open reading frame 24 (C1orf24) exhibited significant down-regulation in all analyses. With FRZB, the pathways were associated with RHO GTPase and elastin fiber formation. With C1orf24, the pathways were elastic fiber formation, extracellular matrix organization, and cell–cell communication. Since only FRZB was evolutionally conserved in the vertebrates, function of FRZB was validated using zebrafish embryos. Knockdown of frzb remarkably reduced vascular integrity in zebrafish embryos. We believe that FRZB is a key gene involved in AAA initiation and progression affecting vascular integrity.     

Early B-cell factors involve in the tumorigenesis and predict the overall survival of gastric cancer

Gastric cancer (GC) is a heavy health burden around the world, which is the fifth most frequent tumor and leads to the third most common cancer-related deaths. It is urgent to identify prognostic markers as the guideline for personalized treatment and follow-up. We accessed the prognostic value of Early B-cell factors (EBFs) in GC. A total of 415 GC tissues and 34 normal tissues from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort, 616 external patients from {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459, {"type":"entrez-geo","attrs":{"text":"GSE22377","term_id":"22377"}}GSE22377, {"type":"entrez-geo","attrs":{"text":"GSE51105","term_id":"51105"}}GSE51105, {"type":"entrez-geo","attrs":{"text":"GSE62245","term_id":"62245"}}GSE62245 were enrolled for analysis. Univariate and multivariate Cox regression analyses were employed to evaluate the sole and integrative prognostic value of EBFs, respectively. Genetic alterations, DNA methylation of EBFs were also evaluated, as well as the involved signaling pathways. We revealed that increased EBFs associated with the poor prognosis of GC patients, the prognostic model was established in TCGA-STAD cohort, and validated in Gene Expression Omnibus (GEO) cohorts, with effectiveness in both HER2 positive and negative patients. DNA methylation was involved in the impact on prognosis. Cell cycle, immune-associated, and MAPK pathways were influenced by EBFs. Anti-CTLA4 immunotherapy is more suitable for EBFs determining high-risk groups, but not anti-PD-1/PD-L1 therapy. 5-Fluorouracil, methotrexate, vorinostat are suitable to inhibit the function of EBFs. Our new findings provide novel insight into the prediction of prognosis and clinical treatment of GC patients based on EBFs.     

High expression of COL5A2, a member of COL5 family,indicates the poor survival and facilitates cell migration in gastric cancer

Background: Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. The present study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC.Methods: The expression, overall survival, and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas (TCGA) database, respectively. Weighted gene co-expression network analysis of the {"type":"entrez-geo","attrs":{"text":"GSE62229","term_id":"62229"}}GSE62229 database was performed out to identify modules and associated genes.Results: COL5A2 was selected as our research target in the TCGA database, and was also verified in the {"type":"entrez-geo","attrs":{"text":"GSE62229","term_id":"62229"}}GSE62229 and {"type":"entrez-geo","attrs":{"text":"GSE15459","term_id":"15459"}}GSE15459 datasets. COL5A2 was up-regulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and {"type":"entrez-geo","attrs":{"text":"GSE62229","term_id":"62229"}}GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.Conclusion: COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.     

Identification of potential biomarkers in dengue via integrated bioinformatic analysis

Dengue fever virus (DENV) is a global health threat that is becoming increasingly critical. However, the pathogenesis of dengue has not yet been fully elucidated. In this study, we employed bioinformatics analysis to identify potential biomarkers related to dengue fever and clarify their underlying mechanisms. The results showed that there were 668, 1901, and 8283 differentially expressed genes between the dengue-infected samples and normal samples in the {"type":"entrez-geo","attrs":{"text":"GSE28405","term_id":"28405"}}GSE28405, {"type":"entrez-geo","attrs":{"text":"GSE38246","term_id":"38246"}}GSE38246, and {"type":"entrez-geo","attrs":{"text":"GSE51808","term_id":"51808"}}GSE51808 datasets, respectively. Through overlapping, a total of 69 differentially expressed genes (DEGs) were identified, of which 51 were upregulated and 18 were downregulated. We identified twelve hub genes, including MX1, IFI44L, IFI44, IFI27, ISG15, STAT1, IFI35, OAS3, OAS2, OAS1, IFI6, and USP18. Except for IFI44 and STAT1, the others were statistically significant after validation. We predicted the related microRNAs (miRNAs) of these 12 target genes through the database miRTarBase, and finally obtained one important miRNA: has-mir-146a-5p. In addition, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out, and a protein–protein interaction (PPI) network was constructed to gain insight into the actions of DEGs. In conclusion, our study displayed the effectiveness of bioinformatics analysis methods in screening potential pathogenic genes in dengue fever and their underlying mechanisms. Further, we successfully predicted IFI44L and IFI6, as potential biomarkers with DENV infection, providing promising targets for the treatment of dengue fever to a certain extent.     

Identification of ribosomal protein family in triple-negative breast cancer by bioinformatics analysis

Triple-negative breast cancer (TNBC) accounts for ∼20% of all breast cancer (BC) cases. The management of TNBC represents a challenge due to its worse prognosis, heterogeneity and lack of targeted therapy. Moreover, its mechanisms are not fully clear. The aim of the study is to identify crucial genes between TNBC and non-TNBC for underlying targets for diagnostic and therapeutic methods of TNBC. The differentially expressed genes (DEGs) between TNBC and non-TNBC were selected from the Gene Expression Omnibus (GEO) database after the integrated analysis of two datasets ({"type":"entrez-geo","attrs":{"text":"GSE65194","term_id":"65194"}}GSE65194 and {"type":"entrez-geo","attrs":{"text":"GSE76124","term_id":"76124"}}GSE76124). Then Gene ontology (GO) and KEGG analysis were performed by DAVID database, protein–protein interaction (PPI) of DEGs was constructed by Search Tool for the Retrieval of Reciprocity Genes (STRING) database. Furthermore, centrality analysis and module analysis were carried out by Cytoscape to analyze the TNBC-related PPI. Subsequently, overall survival (OS) analysis was performed by GEPIA. Finally, the expressions of these key genes in TNBC and non-TNBC tissues were tested by qRT-PCR. The results showed that 955 DEGs were obtained, which were mainly enriched in ribosome, ribosomal subunit, and so on. Moreover, 19 candidate genes were focused on by centrality analysis and module analysis. Furthermore, we found the low expressions of ribosomal protein S9 (RPS9), ribosomal protein S14 (RPS14), ribosomal protein S27 (RPS27), ribosomal protein L11 (RPL11) and ribosomal protein L14 (RPL14) were related to a poor OS in BC patients. Additionally, qRT-PCR results suggested that these five genes were notably down-regulated in TNBC tissues. In summary, the present study suggests that ribosomal proteins are related to TNBC, and they may play an important role in the diagnosis, treatment and prognosis of TNBC.     

Expression of the Genetic Suppressor Element 24.2 (GSE24.2) Decreases DNA Damage and Oxidative Stress in X-Linked Dyskeratosis Congenita Cells

The predominant X-linked form of Dyskeratosis congenita results from mutations in DKC1, which encodes dyskerin, a protein required for ribosomal RNA modification that is also a component of the telomerase complex. We have previously found that expression of an internal fragment of dyskerin ({"type":"entrez-geo","attrs":{"text":"GSE24","term_id":"24"}}GSE24.2) rescues telomerase activity in X-linked dyskeratosis congenita (X-DC) patient cells. Here we have found that an increased basal and induced DNA damage response occurred in X-DC cells in comparison with normal cells. DNA damage that is also localized in telomeres results in increased heterochromatin formation and senescence. Expression of a cDNA coding for {"type":"entrez-geo","attrs":{"text":"GSE24","term_id":"24"}}GSE24.2 rescues both global and telomeric DNA damage. Furthermore, transfection of bacterial purified or a chemically synthesized {"type":"entrez-geo","attrs":{"text":"GSE24","term_id":"24"}}GSE24.2 peptide is able to rescue basal DNA damage in X-DC cells. We have also observed an increase in oxidative stress in X-DC cells and expression of {"type":"entrez-geo","attrs":{"text":"GSE24","term_id":"24"}}GSE24.2 was able to diminish it. Altogether our data indicated that supplying {"type":"entrez-geo","attrs":{"text":"GSE24","term_id":"24"}}GSE24.2, either from a cDNA vector or as a peptide reduces the pathogenic effects of Dkc1 mutations and suggests a novel therapeutic approach.     

Weighted gene coexpression network and experimental analyses identify lncRNA SPRR2C as a regulator of the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis

Psoriasis is a chronic inflammatory disease of the skin with highly complex pathogenesis. In this study, we identified lncRNA SPRR2C (small proline-rich protein 2C) as a hub gene with a critical effect on the pathogenesis of psoriasis and response to treatment using both weighted gene coexpression network analysis (WGCNA) and differential expression analysis. SPRR2C expression was significantly upregulated in both psoriatic lesion samples and HaCaT cell lines in response to IL-22 treatment. After SPRR2C knockdown, IL-22-induced suppression of HaCaT proliferation, changes in the KRT5/14/1/10 protein levels, and suppression of the IL-1β, IL-6, and TNF-α mRNA levels were dramatically reversed. In the coexpression network with SPRR2C based on {"type":"entrez-geo","attrs":{"text":"GSE114286","term_id":"114286"}}GSE114286, miR-330 was significantly negatively correlated with SPRR2C, while STAT1 and S100A7 were positively correlated with SPRR2C. By binding to miR-330, SPRR2C competed with STAT1 and S100A7 to counteract miR-330-mediated suppression of STAT1 and S100A7. MiR-330 overexpression also reversed the IL-22-induced changes in HaCaT cell lines; in response to IL-22 treatment, miR-330 inhibition significantly attenuated the effects of SPRR2C knockdown. STAT1 and S100A7 expression was significantly upregulated in psoriatic lesion samples. The expression of miR-330 had a negative correlation with the expression of SPRR2C, while the expression of SPRR2C had a positive correlation with the expression of STAT1 and S100A7. Thus, SPRR2C modulates the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis. WGCNA might uncover additional biological pathways that are crucial in the pathogenesis and response to the treatment of psoriasis.Subject terms: Cells, Diseases     

Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation

Background: Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) allow entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells and play essential roles in cancer therapy. However, the functions of ACE2 and TMPRSS2 in kidney cancer remain unclear, especially as kidneys are targets for SARS-CoV-2 infection.Methods: UCSC Xena project, the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases ({"type":"entrez-geo","attrs":{"text":"GSE30589","term_id":"30589"}}GSE30589 and {"type":"entrez-geo","attrs":{"text":"GSE59185","term_id":"59185"}}GSE59185) were searched for gene expression in human tissues, gene expression data, and clinical information. Several bioinformatics methods were utilized to analyze the correlation between ACE2 and TMPRSS2 with respect to the prognosis of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP).Results: ACE2 expression was significantly upregulated in tumor tissue, while its downregulation was associated with low survival in KIRC and KIRP patients. TMPRSS2 was downregulated in KIRC and KIRP, and its expression was not correlated with patient survival. According to clinical risk factor-based prediction models, ACE2 exhibits predictive accuracy for kidney cancer prognosis and is correlated with metabolism and immune infiltration. In an animal model, ACE2 expression was remarkably downregulated in SARS-CoV-2-infected cells compared to in the control.Conclusion: ACE2 expression is highly correlated with various metabolic pathways and is involved in immune infiltration.it plays a crucial role than TMPRSS2 in diagnosing and prognosis of kidney cancer patients. The overlap in ACE2 expression between kidney cancer and SARS-CoV-2 infection suggests that patients with KIRC or KIRP are at high risk of developing serious symptoms.     

Immune implication of an autophagy-related prognostic signature in uveal melanoma

Uveal Melanoma (UM) is a rare cancer deriving from melanocytes within the uvea. It has a high rate of metastasis, especially to the liver, and a poor prognosis thereafter. Autophagy, an intracellular programmed digestive process, has been associated with the development and progression of cancers, with controversial pro- and anti-tumour roles. Although previous studies have been conducted on autophagy-related genes (ARGs) in various cancer types, its role in UM requires a deeper understanding for improved diagnosis and development of novel therapeutics. In the present study, Zheng et al. used univariate Cox regression followed by least absolute shrinkage and selection operator (Lasso) regression to identify a robust 9-ARG signature prognostic of survival in a total of 230 patients with UM. The authors used the Cancer Genome Atlas (TCGA) UM cohort as a training cohort (n=80) to identify the signature and validated it in another four independent cohorts of 150 UM patients from the Gene Expression Omnibus (GEO) repository ({"type":"entrez-geo","attrs":{"text":"GSE22138","term_id":"22138"}}GSE22138, {"type":"entrez-geo","attrs":{"text":"GSE27831","term_id":"27831"}}GSE27831, {"type":"entrez-geo","attrs":{"text":"GSE44295","term_id":"44295"}}GSE44295 and {"type":"entrez-geo","attrs":{"text":"GSE84976","term_id":"84976"}}GSE84976). This 9-ARG signature was also significantly associated with the enrichment of cancer hallmarks, including angiogenesis, IL6-KJAK-STAT3 signalling, reactive oxygen species pathway and oxidative phosphorylation. More importantly, this signature is associated with immune-related functional pathways and immune cell infiltration. Thus, this 9-ARG signature predicts prognosis and provides deeper insights into the immune mechanisms in UM, with potential implications for future immunotherapy.