Screening of colorectal cancer associated lncRNA, miRNA and mRNA based on bioinformatics technology and analysis of their biological functions / 中国肿瘤生物治疗杂志

@# Objective: To screen differentially expressed lncRNA, miRNA and mRNA in colorectal cancer (CRC) in TCGA database, and to explore their relationship with CRC prognosis and related biological functions. Methods: RNA sequencing (RNA-Seq) data and miRNA-Seq data of CRC samples were downloaded from the TCGAdatabase and analyzed, and differentially expressed lncRNA, miRNA and mRNA were screened by R program. The lncRNA-miRNA-mRNA ceRNA network in CRC was constructed by analyzing and integrating the relationships between differentially expressed RNAs through miRcode, TargetScan and miRTarbase databases.KaplanMeier method was used to analyze the relationship between the expression of lncRNA, miRNA, mRNA in ceRNA network and the survival prognosis of patients.Finally, the signal pathways involved in the occurrence and development of CRC were analyzed by GSEA functional enrichment analysis software. Results: A total of 614 differentially expressed lncRNAs, 244 differentially expressed miRNAs, and 12 672 differentially expressed mRNAs in CRC were identified; a ceRNA network consisting of 139 lncRNAs, 37 miRNAs and 228 mRNAs was constructed;It was found that 58 lncRNAs, 23 miRNAs, and 150 mRNAs were associated with the prognosis of CRC.The results of GSEA enrichment analysis showed that mRNA was mainly involved in signaling pathways such as Notch, Hedgehog and TGF-β. Conclusion: CRC-related ceRNA network was successfully constructed and lncRNAs, miRNAs and mRNAs associated with CRC prognosis were screened. It provides a valuable preliminary basis for further in-depth clinical research and basic experimental research on CRC.

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods

Aortic dissection is characterized by the redirection of blood flow, which flows through an intimal tear into the aortic media. The purpose of this study was to find potential acute type A aortic dissection (AAAD)-related genes and molecular mechanisms by bioinformatics. The gene expression profiles of GSE52093 were obtained from Gene Expression Omnibus (GEO) database, including 7 AAAD samples and 5 normal samples. The differentially expressed genes (DEGs) were detected between AAAD and normal samples. The functional annotation and pathway enrichment analysis were conducted through the Database for Annotation, Visualization and Integration Discovery (DAVID). A protein-protein interaction network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) software. The microRNAs (miRNAs) of these differentially expressed genes were predicted using <microRNA.org> database. Moreover, DEGs were analyzed in the comparative toxicogenomics (CTD) database to screen out the potential therapeutic small molecules. As a result, there were 172 DEGs identified in patients with AAAD. These DEGs were significantly enriched in 6 pathways, including cell cycle, oocyte meiosis, DNA replication, extracellular matrix-receptor interaction, and mineral absorption pathway. Notably, CDC20, CDK1, CHEK1, KIF20A, MCM10, PBK, PTTG1, RACGAP, and TOP2A were crucial genes with a high degree in the protein-protein interaction network. Furthermore, potential miRNAs (miR-301, miR-302 family, and miR-130 family) were identified. In addition, small molecules like azathioprine and zoledronic acid were identified to be potential drugs for AAAD.

Candidate genes and pathogenesis investigation for sepsis-related acute respiratory distress syndrome based on gene expression profile

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. RESULTS: A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. CONCLUSIONS: Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS

Perfil de transcrição gênica de células humanas estimuladas com a saliva de Lu. intermedia ou de Lu / Gene transcription profile of human cells stimulated with Lu saliva. Intermedia or Lu

A saliva dos flebotomíneos transmissores do parasita Leishmania possui uma variedade de agentes farmacológicos, como anticoagulantes, vasodilatadores além de moléculas imunomoduladoras e anti-inflamatórias. A saliva de Lu. intermedia e de Lu. longipalpis provocam o aumentam da infecção por diferentes espécies de Leishmania, em modelos experimentais.Entretanto a pré-exposição à saliva de Lu. longipalpis confere proteção a infecção, enquanto a pré-exposição à saliva de Lu. intermedia causa exacerbação da doença. Neste trabalho estimulamos as células do sangue de voluntários sadios com a saliva de Lu. intermedia ou de Lu. longipalpis e, posteriormente, o RNA foi extraído e utilizado no sequenciamento em larga escala (RNAseq). O estudo demonstrou que a saliva de Lu. intermedia e de Lu.longipalpismodula a expressão de uma série de genes e os processos biológicos mais requentes são semelhantes após a estimulação com as duas diferentes salivas. Identificamos seis processos biológicos comuns às salivas dos dois lebotomineos:Taxis,Chemotaxis,Locomotory behavior, Positive regulation of immune system process, Regulation of cytokine production e Regulation of cell activation. Dentre os genes que caracterizam esses seis processos,detectamosgenes que codificam quimiocinas, citocinas além de moléculas de superfície tais como CCL19, CCL2, CCL3, CCL4, CD80, CD83, IL10, IL1B, IL4, IL6.Definimos um conjunto de genes encontrados exclusivamente na amostra estimulada com a saliva de Lu. intermedia (ADA, CCL23, CCL3, CCL3L1, CXCL11, PDGFB, PDPN, PLAU e TNFSF15). Da mesma forma, encontramos um outro conjunto de genes expresso exclusivamenteem células estimuladas com a saliva de Lu. longipalpis(ENPP2, EREG, IDO1,IL1A e VEGFA). Essas diferenças podem fornecer pistas para o desenvolvimento da leishmaniose em indivíduos continuamente expostos à saliva de Lu. intermedia.

The saliva of sand flies, vectors of leishmania parasite, has a variety of pharmacological agents, such as anticoagulants, vasodilators as well as immunomodulatory and antiinflammatory molecules. Lu. intermedia and Lu. longipalpis increase the infection by different species of leishmania in experimental models. However, the pre-exposure to Lu. longipalpis saliva provides protection to infection, while the pre-exposure Lu. intermedia saliva causes exacerbation of the disease. In this work, we stimulated peripheral blood cells from healthy volunteers with salivary glands from Lu. intermedia or Lu. longipalpis and later RNA was extracted and used in large-scale sequencing (RNAseq). This study demonstrated that Lu. intermedia and Lu. longipalpis saliva modulate the expression of a number of genes and the most frequent biological processes are similar in cells stimulated with both saliva. We identified six biological processes commonly upregulated following stimulation with saliva of the two sand flies: taxis, chemotaxis, locomotory behavior, positive regulation of immune system process, regulation of cytokine production and regulation of cell activation. Among the genes that characterize these six biological processes, we detected genes encoding chemokines, cytokines plus surface molecules such as:CCL19, CCL2, CCL3, CCL4, CD80, CD83, IL10, IL1B, IL4 and IL6. We found a set of genes upregulated exclusively in cells stimulated with Lu. intermedia saliva (ADA, CCL23, CCL3, CCL3L1, CXCL11, PDGFB, PDPN, PLAU and TNFSF15). Similarly, another set of genes was expressed only in cells stimulated Lu. longipalpis saliva (ENPP2, EREG, IDO1,IL1A and VEGFA). These differences may provide clues for the development of leishmaniasis in individuals continuously exposed to Lu. intermedia saliva.

Identification of molecular targets in the response of triple negative breast cancer to chemotherapy / 国际生物医学工程杂志

Objective To explore the molecular targets and mechanisms that could influence the sensitivity of triple negative breast cancer (TNBC) to chemotherapy,to provide important references for the chemotherapy based on gene detection.Methods The gene expression dataset GSE43502 was downloaded from the Gene Expression Omnibus in National Center for Biotechnology Information (NCBI).Gene expression data preprocessing was conducted by R Programming.The differentially expressed genes in the TNBC patients that relapsed after chemotherapy compared with the non-relapsed ones were obtained.Besides,the Database for Annotation Visualization and Integrated analysis (DAVID) was used for functional analysis of those genes.The microRNA (miRNA) that might regulate the differentially expressed genes was obtained from the starBase database.Furthermore,Cytoscape was used for the construction of miRNA-gene regulation network.Results Three hundred and twelve differentially expressed genes were obtained.Some biological process related to cell membrane,metal ion homeostasis and pathways involved in immune and inflammatory were found to be enriched in those genes.Furthermore,171 miRNA that might regulate the differentially expressed genes were obtained and 553 miRNA-gene regulation pairs were formed.Conclusions hsa-miR-30d-5p,SIX4,etc.might influence the sensitivity of TNBC to chemotherapy through cell structure or immune system.