Project description:Application of EIIP / ISM bioinformatics platform in detection of new therapeutic targets and potential therapeutic molecules. Study of the molecular basis of rare human diseases
Project description:Little has been known about the role of long non-coding RNA (lncRNA) involves in meniscus degradation with aging.In order to investigate the molecular mechanisms of age-related meniscal degeneration and further explore potential biologic therapeutic targets, we performed microarray analysis of meniscus to determine lncRNAs and mRNAs expression profiles in young and aging adults. Then, we carried out bioinformatics analysis of differentially expressed molecules to identify key molecules and functional pathways in the aged meniscus tissues.
Project description:Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nucleotides, which do not encode proteins (non-coding), yet they participate in the regulation of gene expression through multiple mechanisms in the form of RNA. A total of 51 lncRNAs and 21 mRNAs whose expression changed significantly, were identified. Five deregulated lncRNAs and five mRNAs were confirmed by quantitative real-time polymerase chain reaction (PCR) in 10 paired samples. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of the deregulated genes. Furthermore, correlated expression networks of coding-noncoding co-expression (CNC) was constructed by using bioinformatics methods. We predicted the potential targets of lncRNAs by using bioinformatics methods. In summary, novel lnRNAs were identified as potential biomarkers and therapeutic targets for POCD treatment.
Project description:We hypothesized that circulating miRNAs could work as biomarkers for early detection of breast cancer brain metastasis (BCBM), and their targets could constitute new targets for modulation. We used a mouse model of BCBM and Next-Generation Sequencing to establish the circulating miRNAs alterations along brain metastasis development and performed bioinformatics analysis to identify their targets with relevance in the metastatic process. We additionally analyzed human resected brain metastasis of breast cancer patients for target’s expression validation. In our mouse model, we observed a deregulation of circulating miRNAs profile during BCBM progression, with a downregulation of miR-802-5p and miR-194-5p in plasma prior to brain metastases detection. The transcription factor myocyte enhancer factor 2C (MEF2C), was identified as a target for both miRNAs, and its expression was increasingly observed in malignant cells along brain metastasis development. Its upregulation was also observed in peritumoral astrocytes and in human BCBM. Collectively, downregulation of circulating miR-802-5p and miR-194-5p appear as precocious biomarkers for BCBM and MEF2C emerges as a new player and a potential target for modulation.
Project description:The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression. Keywords: ordered
Project description:To search for new therapeutic targets for type 1 & 2 diabetes, we have applied genome wide transcriptional profiling and systems biology oriented bioinformatics analysis to examine the impact of the Power mix(PM) and Alpha-1 Anti-Trypsin( AAT) regimens upon pancreatic lymph node (PLN) and fat, a crucial tissue for insulin dependent glucose disposal, in new onset diabetic NOD mice. Transcriptional profiles of fat and PLNs in normal (non diabetic) NOD mice (NOR), new onset diabetic (DIA), new onset diabetic NOD mice treated with AAT or PM were perfromed in this study
Project description:We first use microRNA expression profiles to find miRNA expression signatures in 3 cases of human angiosarcoma and capillary hemangiomauman, then RT-PCR for large sample verification. Through the bioinformatics prediction of its target genes, we study its function and aim to find the new molecular markers and therapeutic targets. We identified the miRNA expression signatures in human angiosarcomas and capillary hemangiomas by using microRNA expression profiles
Project description:Epithelial ovarian cancer (EOC) constitutes a major gynecological malignancy, with a reported incidence rate of 3-12/100 000 woman annually. As early symptoms of ovarian cancer are often clinically atypical or absent, the majority of ovarian cancer patients are diagnosed at a late stage, when the five-year survival rate is extremely low. This condition underscores the urgency of early detection of these patients and establishment of new therapeutic targets for successful intervention. Considering that the predominant biological characteristic that differentiates malignant from benign tumors is the ability to metastasize, it is necessary to identify novel metastasis-related molecules for ovarian cancer. In this study, we found that CAFs could significantly increase the metastatic potential of ovarian cancer cells compared with non-cancer associated fibroblasts(NAFs), which is associated with over-expression of CXCL14 in CAFs. We examined the impact of CAF-secreted CXCL14 on the lncRNA expression profiles in ovarian cancer during metastasis. We treated A2780s ovarian cancer cell line with recombinant CXCL14 protein and control respectively and subjected them to Arraystar Human LncRNA microarray v3.0 to profile differential lncRNAs in ovarian cancer upon treatment of CXCL14
Project description:Medulloblastoma (MB) is the most common pediatric malignant brain tumor and patients with a high-risk or recurrent MB respond poorly to current therapies, with higher related mortality. Potential molecules related to MB must be identified to develop targets for therapeutic development. In the present study, we compared MB microarray data obtained using different microarray systems and significant targets were selected by gene annotation and enrichment analysis. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function “vesicle” were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), had significantly lower expression levels in MB. In addition, SNAP25 was detected in a very low number of MB cells according to western blot analysis and immunohistochemical analyses of archived and formalin-fixed/paraffin-embedded human MB specimens. We found that SNAP25 could change the morphology and the chemotherapeutic effect of arabinofuranosyl cytidine (Ara-C) on SNAP25-expressing MB cells. In conclusion, the expression of SNAP25 is crucial for the dendrite formation and correlate to the targeted chemotherapy. The detection of SNAP25 expression in MB cells may be essential for the chemotherapeutic application of Ara-C.