An epithelial–mesenchymal transition-related long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer

Bladder cancer is a common malignant tumour worldwide. Epithelial–mesenchymal transition (EMT)-related biomarkers can be used for early diagnosis and prognosis of cancer patients. To explore, accurate prediction models are essential to the diagnosis and treatment for bladder cancer. In the present study, an EMT-related long noncoding RNA (lncRNA) model was developed to predict the prognosis of patients with bladder cancer. Firstly, the EMT-related lncRNAs were identified by Pearson correlation analysis, and a prognostic EMT-related lncRNA signature was constructed through univariate and multivariate Cox regression analyses. Then, the diagnostic efficacy and the clinically predictive capacity of the signature were assessed. Finally, Gene set enrichment analysis (GSEA) and functional enrichment analysis were carried out with bioinformatics. An EMT-related lncRNA signature consisting of TTC28-AS1, LINC02446, {"type":"entrez-nucleotide","attrs":{"text":"AL662844.4","term_id":"17978158","term_text":"AL662844.4"}}AL662844.4, {"type":"entrez-nucleotide","attrs":{"text":"AC105942.1","term_id":"18129419","term_text":"AC105942.1"}}AC105942.1, {"type":"entrez-nucleotide","attrs":{"text":"AL049840.3","term_id":"7406443","term_text":"AL049840.3"}}AL049840.3, SNHG26, USP30-AS1, PSMB8-AS1, {"type":"entrez-nucleotide","attrs":{"text":"AL031775.1","term_id":"4071041","term_text":"AL031775.1"}}AL031775.1, {"type":"entrez-nucleotide","attrs":{"text":"AC073534.1","term_id":"8655969","term_text":"AC073534.1"}}AC073534.1, {"type":"entrez-nucleotide","attrs":{"text":"U62317.2","term_id":"6862558","term_text":"U62317.2"}}U62317.2, C5orf56, {"type":"entrez-nucleotide","attrs":{"text":"AJ271736.1","term_id":"8979791","term_text":"AJ271736.1"}}AJ271736.1, and {"type":"entrez-nucleotide","attrs":{"text":"AL139385.1","term_id":"6996206","term_text":"AL139385.1"}}AL139385.1 was constructed. The diagnostic efficacy of the signature was evaluated by the time-dependent receiver-operating characteristic (ROC) curves, in which all the values of the area under the ROC (AUC) were more than 0.73. A nomogram established by integrating clinical variables and the risk score confirmed that the signature had a good clinically predict capacity. GSEA analysis revealed that some cancer-related and EMT-related pathways were enriched in high-risk groups, while immune-related pathways were enriched in low-risk groups. Functional enrichment analysis showed that EMT was associated with abundant GO terms or signaling pathways. In short, our research showed that the 14 EMT-related lncRNA signature may predict the prognosis and progression of patients with bladder cancer.     

NF-κB-mediated lncRNA AC007271.3 promotes carcinogenesis of oral squamous cell carcinoma by regulating miR-125b-2-3p/Slug

Oral squamous cell carcinoma (OSCC) is the most common oral cancer. The molecular mechanisms of this disease are not fully understood. Our previous studies confirmed that dysregulated function of long non-coding RNA (lncRNA) {"type":"entrez-nucleotide","attrs":{"text":"AC007271.3","term_id":"7408074","term_text":"AC007271.3"}}AC007271.3 was associated with a poor prognosis and overexpression of {"type":"entrez-nucleotide","attrs":{"text":"AC007271.3","term_id":"7408074","term_text":"AC007271.3"}}AC007271.3 promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of {"type":"entrez-nucleotide","attrs":{"text":"AC007271.3","term_id":"7408074","term_text":"AC007271.3"}}AC007271.3 dysregulation remained obscure. In this study, our investigation showed that {"type":"entrez-nucleotide","attrs":{"text":"AC007271.3","term_id":"7408074","term_text":"AC007271.3"}}AC007271.3 functioned as competing endogenous RNA by binding to miR-125b-2-3p and by destabilizing primary miR-125b-2, resulted in the upregulating expression of Slug, which is a direct target of miR-125b-2-3p. Slug also inhibited the expression of E-cadherin but N-cadherin, vimentin, and β-catenin had no obvious change. The expression of {"type":"entrez-nucleotide","attrs":{"text":"AC007271.3","term_id":"7408074","term_text":"AC007271.3"}}AC007271.3 was promoted by the canonical nuclear factor-κB (NF-κB) pathway. Taken together, these results suggested that the classical NF-κB pathway-activated {"type":"entrez-nucleotide","attrs":{"text":"AC007271.3","term_id":"7408074","term_text":"AC007271.3"}}AC007271.3 regulates EMT by miR-125b-2-3p/Slug/E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.Subject terms: Metastasis, Oral cancer     

The selective alpha7 nicotinic acetylcholine receptor agonist AR-R17779 does not affect ischemia–reperfusion brain injury in mice

Inflammation plays a central role in stroke-induced brain injury. The alpha7 nicotinic acetylcholine receptor (α7nAChR) can modulate immune responses in both the periphery and the brain. The aims of the present study were to investigate α7nAChR expression in different brain regions and evaluate the potential effect of the selective α7nAChR agonist AR-{"type":"entrez-nucleotide","attrs":{"text":"R17779","term_id":"771389"}}R17779 on ischemia–reperfusion brain injury in mice. Droplet digital PCR (ddPCR) was used to evaluate the absolute expression of the gene encoding α7nAChR (Chrna7) in hippocampus, striatum, thalamus and cortex in adult, naïve mice. Mice subjected to transient middle cerebral artery occlusion (tMCAO) or sham surgery were treated with α7nAChR agonist AR-{"type":"entrez-nucleotide","attrs":{"text":"R17779","term_id":"771389"}}R17779 (12 mg/kg) or saline once daily for 5 days. Infarct size and microglial activation 7 days after tMCAO were analyzed using immunohistochemistry. Chrna7 expression was found in all analyzed brain regions in naïve mice with the highest expression in cortex and hippocampus. At sacrifice, white blood cell count was significantly decreased in AR-{"type":"entrez-nucleotide","attrs":{"text":"R17779","term_id":"771389"}}R17779 treated mice compared with saline controls in the sham groups, although, no effect was seen in the tMCAO groups. Brain injury and microglial activation were evident 7 days after tMCAO. However, no difference was found between mice treated with saline or AR-{"type":"entrez-nucleotide","attrs":{"text":"R17779","term_id":"771389"}}R17779. In conclusion, α7nAChR expression varies in different brain regions and, despite a decrease in white blood cells in sham mice receiving AR-{"type":"entrez-nucleotide","attrs":{"text":"R17779","term_id":"771389"}}R17779, this compound does not affect stroke-induced brain injury.     

Peroxiredoxin alleviates the fitness costs of imidacloprid resistance in an insect pest of rice

Chemical insecticides have been heavily employed as the most effective measure for control of agricultural and medical pests, but evolution of resistance by pests threatens the sustainability of this approach. Resistance-conferring mutations sometimes impose fitness costs, which may drive subsequent evolution of compensatory modifier mutations alleviating the costs of resistance. However, how modifier mutations evolve and function to overcome the fitness cost of resistance still remains unknown. Here we show that overexpression of P450s not only confers imidacloprid resistance in the brown planthopper, Nilaparvata lugens, the most voracious pest of rice, but also leads to elevated production of reactive oxygen species (ROS) through metabolism of imidacloprid and host plant compounds. The inevitable production of ROS incurs a fitness cost to the pest, which drives the increase or fixation of the compensatory modifier allele {"type":"entrez-nucleotide","attrs":{"text":"T65549","term_id":"674594","term_text":"T65549"}}T65549 within the promoter region of N. lugens peroxiredoxin (NlPrx) in the pest populations. {"type":"entrez-nucleotide","attrs":{"text":"T65549","term_id":"674594","term_text":"T65549"}}T65549 allele in turn upregulates the expression of NlPrx and thus increases resistant individuals’ ability to clear the cost-incurring ROS of any source. The frequent involvement of P450s in insecticide resistance and their capacity to produce ROS while metabolizing their substrates suggest that peroxiredoxin or other ROS-scavenging genes may be among the common modifier genes for alleviating the fitness cost of insecticide resistance.

This study shows that peroxiredoxin is a modifier gene whose cis-upregulation in the brown planthopper (Nilaparvata lugens) increases the ability of resistant populations to clear the fitness cost-incurring reactive oxygen species that inevitably result from P450-meditated metabolism of imidacloprid insecticide.     

MiR‐29 coordinates age‐dependent plasticity brakes in the adult visual cortex

The authors regret having omitted grant attributions in the original publication. The funding section is herewith updated to reflect the change. “Funding attributed to Tommaso Pizzorusso was provided by EPIGEN Flagship project and PRIN2017HM8FA, funding attributed to Alessandro Cellerino was provided by Fondazione Pisa ETHERNA project, funding attributed to Pierre Baldi was provided by NIH (grant NIH {"type":"entrez-nucleotide","attrs":{"text":"GM123558","term_id":"221306858","term_text":"GM123558"}}GM123558), funding attributed to Jessica Kwok was provided by the Leverhulme Trust project grant (RPG‐2018‐100).”     

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.     

The fructose-1,6-bisphosphatase deficiency and the p.(Lys204ArgfsTer72) variant

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inborn error of fructose metabolism caused by pathogenic variants in the FBP1 gene. As gluconeogenesis is affected, catabolic episodes can induce ketotic hypoglycemia in patients. FBP1 analysis is the most commonly used approach for the diagnosis of this disorder. Herein, a Brazilian patient is reported. The proband, a girl born to a consanguineous couple, presented with severe hypoglycemia crisis in the neonatal period. At the age 17 months, presented a new crisis accompanied by metabolic acidosis associated with a feverish episode. Genetic analysis was performed by next-generation sequencing (NGS), identifying the {"type":"entrez-nucleotide","attrs":{"text":"NM_000507.3","term_id":"160298191","term_text":"NM_000507.3"}}NM_000507.3:c.611_614del variant in homozygosis in the FBP1 gene. In silico analysis and 3D modeling were performed, suggesting that this variant is associated with a loss of sites for substrate and Mg²⁺ binding and for posttranslational modifications of FBPase. The c.611_614del variant is located in a repetitive region of the FBP1 gene that appears to be a hotspot for mutational events. This frameshift creates a premature termination codon in the last coding exon which escapes the nonsense-mediated decay mechanism, according to in silico analysis. This variant results in an intrinsically disordered protein with loss of substrate recognition and post-translational modification sites.     

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.     

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.     

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     

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.     

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.     

Morphological and Molecular Identification of Spirometra Tapeworms (Cestoda: Diphyllobothriidae) from Carnivorous Mammals in the Serengeti and Selous Ecosystems of Tanzania

Spirometra tapeworms (Cestoda: Diphyllobothriidae) collected from carnivorous mammals in Tanzania were identified by the DNA sequence analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) and internal transcribed spacer 1 (ITS1), and by morphological characteristics. A total of 15 adult worms were collected from stool samples and carcasses of Panthera leo, Panthera pardus, and Crocuta crocuta in the Serengeti and Selous ecosystems of Tanzania. Three Spirometra species: S. theileri, S. ranarum and S. erinaceieuropaei were identified based on morphological features. Partial cox1 sequences (400 bp) of 10 specimens were revealed. Eight specimens showed 99.5% similarity with Spirometra theileri ({"type":"entrez-nucleotide","attrs":{"text":"MK955901","term_id":"1796114604","term_text":"MK955901"}}MK955901), 1 specimen showed 99.5% similarity with the Korean S. erinaceieuropaei and 1 specimen had 99.5% similarity with Myanmar S. ranarum. Sequence homology estimates for the ITS1 region of S. theileri were 89.8% with S. erinaceieuropaei, 82.5% with S. decipiens, and 78.3% with S. ranarum; and 94.4% homology was observed between S. decipiens and S. ranarum. Phylogenetic analyses were performed with 4 species of Spirometra and 2 species of Dibothriocephalus (=Diphyllobothrium). By both ML and BI methods, cox1 and ITS1 gave well supported, congruent trees topology of S. erinaceieuropaei and S. theileri with S. decipiens and S. ranarum forming a clade. The Dibothriocephalus species were sisters of each other and collectively forming successive outgroups. Our findings confirmed that 3 Spirometra species (S. theileri, S. ranarum, and S. erinaceieuropaei) are distributed in the Serengeti and Selous ecosystems of Tanzania.     

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 immune-related lncRNAs to improve the prognosis prediction for patients with papillary thyroid cancer

Objective: To identify immune-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC).Methods: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to obtain the gene expression profile. Immune-related lncRNAs were screened from the Molecular Signatures Database v4.0 (MsigDB). We performed a survival analysis of critical lncRNAs. Further, the function of prognostic lncRNAs was inferred using the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) to clarify the possible mechanisms underlying their predictive ability. The assessment was performed in clinical samples and PTC cells.Results: We obtained 4 immune-related lncRNAs, 15 microRNAs (miRNAs), and 375 mRNAs as the key mediators in the pathophysiological processes of PTC from the GEO database. Further, Lasso regression analysis identified seven prognostic markers (LINC02550, SLC26A4-AS1, ACVR2B-AS1, {"type":"entrez-nucleotide","attrs":{"text":"AC005479.2","term_id":"4508155","term_text":"AC005479.2"}}AC005479.2, LINC02454, and AL136366.1), most of which were related to tumor development. The KEGG pathway enrichment analysis showed different, changed genes mainly enriched in the cancer-related pathways, PI3K-Akt signaling pathway, and focal adhesion. Only SLC26A4-AS1 had an intersection in the results of the two databases.Conclusion: LncRNA SLC26A4-AS1, which is the most associated with prognosis, may play an oncogenic role in the development of PTC.     

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.     

STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells

Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca²⁺. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca²⁺ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from {"type":"entrez-protein","attrs":{"text":"SKF96365","term_id":"1156357400","term_text":"SKF96365"}}SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in {"type":"entrez-protein","attrs":{"text":"SKF96365","term_id":"1156357400","term_text":"SKF96365"}}SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.Subject terms: Tumour angiogenesis, Cancer microenvironment