Applications of RNA-Seq technology on medicinal plants / 中草药

RNA-Sequencing (RNA-Seq) is a newly developed method to analyze gene function and interaction at the omics level, which is widely used in frontier field in molecular biology and other fields. In recent years, this technology has been intensively used in the research of medicinal plants, and growing number of reports are published. This paper systematically sorted out relevant literatures and summarized applications of RNA-Seq technology in functional gene discovery, gene network analysis, genetic mechanism revelation and development of molecular marker of medicinal plants. Meanwhile, according to the technical characteristics of RNA-Seq and the development needs of medicinal plant research, this article brings the future prospects regarding RNA-seq technology in Chinese medicinal materials, and intending to provide inspirations for researches on Chinese materia medica based on RNA-Seq.

Bioinformatics analysis and functional analysis of bladder cancer gene microarray / 解剖学报

Objective To explore the pathogenesis of bladder cancer from the molecular level and provide new ideas for clinical diagnosis and prognosis evaluation. Methods Human bladder cancer-associated gene chip data GSE31189, including 52 bladder cancer samples and 40 normal bladder samples, was downloaded from a database of gene chips, and then Morpheus (https://software.broadinstitute.org/morpheus/) online tools were used to analyze cancer urothelial tissue and normal urothelial tissue. Differentially expressed genes were then analyzed online using gene-cloud of biotechnology information(GOBI) (https://www.GCBI.com.cn) for enrichment of differentially expressed gene signaling pathways and differential gene interactions. Finally, differential selection genes were selected for cell counting kit-8(CCK-8) , invasion and Western blotting assays. Initially verify its function. Results According to the q value, the top 20 genes with the largest difference were selected. Among them, 18 genes were up-regulated and 2 genes were down-regulated in bladder cancer. Gene ontology(GO)analysis revealed that these differentially expressed genes are mainly involved in many biological functions such as inflammatory responses, immune responses, negative regulation of apoptosis, and transcriptional negative control from the RNA polymerase D promoter. Pathway analysis showed that these differentially expressed genes are involved in biological processes such as transcriptional dysregulation, metabolic pathways, and nuclear factor kappa beta (NF-kB) signaling pathways in cancer. Gene network analysis found that CXC chemokine receptor 4 (CXCR4) and mitogen-activated protein kinase 10 (MAPK10) are the central links in these gene networks. In vitro experiments showed that matrix metalloproteindase-12 (MMP-12) downregulation led to the decreased proliferation and invasion of bladder cancer cells and the phosphorylation level of extracellular regulated protein kinases(ERK). Conclusion Multiple bioinformatics analysis can identify the key genes in bladder tumors. CXCR4 and MAPK10 are the key links in the bladder gene network. MMP-12 is highly expressed in bladder cancer cells. Downregulation of MMP-12 can inhibit the proliferation and invasion abilities of bladder cancer cells through ERK pathway.

PTMD: A Database of Human Disease-associated Post-translational Modifications / 基因组蛋白质组与生物信息学报·英文版

Various posttranslational modifications (PTMs) participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in human diseases. Therefore, an integral resource of PTM-disease associations (PDAs) would be a great help for both academic research and clinical use. In this work, we reported PTMD, a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of disease-associated PTM events. By reconstructing a disease-gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http://ptmd.biocuckoo.org.

Bioinformatics analysis of microarray data to reveal the pathogenesis of diffuse intrinsic pontine glioma

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is the main cause of pediatric brain tumor death. This study was designed to identify key genes associated with DIPG. METHODS: The gene expression profile GSE50021, which consisted of 35 pediatric DIPG samples and 10 normal brain samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by limma package. Functional and pathway enrichment analyses were performed by the DAVID tool. Protein-protein interaction (PPI) network, and transcription factor (TF)-microRNA (miRNA)-target gene network were constructed using Cytoscape. Moreover, the expression levels of several genes were validated in human glioma cell line U251 and normal glia HEB cells through real-time polymerase chain reaction (PCR). RESULTS: A total of 378 DEGs were screened (74 up-regulated and 304 down-regulated genes). In the PPI network, GRM1, HTR2A, GRM7 and GRM2 had higher degrees. Besides, GRM1 and HTR2A were significantly enriched in the neuroactive ligand-receptor interaction pathway, and calcium signaling pathway. In addition, TFAP2C was a significant down-regulated functional gene and hsa-miR-26b-5p had a higher degree in the TF-miRNA-target gene network. PCR analysis revealed that GRM7 and HTR2A were significantly downregulated while TFAP2C was upregulated in U251 cells compared with that in HEB cells (p < 0.001). GRM2 was not detected in cells. CONCLUSIONS: GRM1 and HTR2A might function in DIPG through the neuroactive ligand-receptor interaction pathway and the calcium signaling pathway. Furthermore, the TFAP2C and hsa-miR-26b-5p might play important roles in the development and progression mechanisms of DIPG.

Recent developments in pathogenesis of Hirschsprung's disease / 中华实用儿科临床杂志

Hirschsprung's disease (HD) is a conginental disorder of enteric nervous system (ENS) and is associated with the abnormal migration of gut neural cerst cell (GNCC).Recent studies showed that the regulation of this migration is a complex gene network.By the development of epigenetic and stem cells,this network is becoming much more clear.Transplantation of the modified gut neural crest stem cells/gut neural crest precursors(GNCSC/GNCP) acquired from the HD bowl is becoming the potential therapy of HD.This paper summerizes the recent advances and is to promote better understanding the pathogenesis of HD.

On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors

In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.

Modeling Colon Cancer Gene Logic Network With mRNA Microarray Data / 生物化学与生物物理进展

Analysis of cellular pathways and networks in terms of logic relations is important to decipher the networks of molecular interactions that underlie cellular function.A computational approach for identifying lower and higher order gene logic associations was presented on the base of graph coloring theory and applied it to the colon cancer mRNA microarray data.Then the logic relationships of 51 oncogenes and cancer suppressor genes are analyzed and the logic association network of them was constructed.The signal pathway of TGF? from the network model was found and verified by the colon cancer pathway of KEGG.The model reveals many higher order logic relationships of cancer genes.These relationships illustrate the complexities that arise in cancer cellular networks because of interacting pathways.The results show that this method is feasible and is expected to give a reference to the medical molecular biologist.