Biomedical subjects

Zhong-Hui Duan

Publications and source records attributed to Zhong-Hui Duan.

5 recordsLinked to original sources

PubMed2006

The relationship between protein sequences and their gene ontology functions.

BACKGROUND: One main research challenge in the post-genomic era is to understand the relationship between protein sequences and their biological functions. In recent years, several automated annotation systems have been developed for the functional assignment of uncharacterized proteins. The underlying assumption of these systems is that similar sequences imply similar biological functions. However, it has been noted that matching sequences do not always infer similar functions. RESULTS: In this paper, we present the correlation between protein sequences and protein functions for the yeast proteome in the context of gene ontology. A novel measure is introduced to define the overall similarity between two protein sequences. The effects of the level as well as the size of a gene ontology group on the degree of similarity were studied. The similarity distributions at different levels of gene ontology trees are presented. To evaluate the theoretical prediction power of similar sequences, we computed the posterior probability of correct predictions. CONCLUSION: The results indicate that protein pairs of similar biological functions tend to have higher sequence similarity, although the similarity distribution in each functional group is heterogeneous and varies from group to group. We conclude that sequence similarity can serve as a key measure in protein function prediction. However, the resulting annotations must be verified through other means. A method that combines a broader range of measures is more likely to provide more accurate prediction. Our study indicates that the posterior probability of a correct prediction could serve as one of the key measures.

Amino Acid Sequence↗

PubMed2006

Novel alpha1-adrenergic receptor signaling pathways: secreted factors and interactions with the extracellular matrix.

alpha1-Adrenergic receptor (alpha1-ARs) subtypes (alpha1A, alpha1B, and alpha1D) regulate multiple signal pathways, such as phospholipase C, protein kinase C (PKC), and mitogen-activated protein kinases. We employed oligonucleotide microarray technology to explore the effects of both short- (1 h) and long-term (18 h) activation of the alpha1A-AR to enable RNA changes to occur downstream of earlier well characterized signaling pathways, promoting novel couplings. Polymerase chain reaction (PCR) studies confirmed that PKC was a critical regulator of alpha1A-AR-mediated gene expression, and secreted interleukin (IL)-6 also contributed to gene expression alterations. We next focused on two novel signaling pathways that might be mediated through alpha1A-AR stimulation because of the clustering of gene expression changes for cell adhesion/motility (syndecan-4 and tenascin-C) and hyaluronan (HA) signaling. We confirmed that alpha1-ARs induced adhesion in three cell types to vitronectin, an interaction that was also integrin-, FGF7-, and PKC-dependent. alpha1-AR activation also inhibited cell migration, which was integrin- and PKC-independent but still required secretion of FGF7. alpha1-AR activation also increased the expression and deposition of HA, a glycosaminoglycan, which displayed two distinct structures: pericellular coats and long cable structures, as well as increasing expression of the HA receptor, CD44. Long cable structures of HA can bind leukocytes, which this suggests that alpha1-ARs may be involved in proinflammatory responses. Our results indicate alpha1-ARs induce the secretion of factors that interact with the extracellular matrix to regulate cell adhesion, motility and proinflammatory responses through novel signaling pathways.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2004

Effects of resveratrol on gene expression in renal cell carcinoma.

Studies have shown that Resveratrol (RE) can inhibit cancer initiation, promotion, and progression. However the gene expression profile in renal cell carcinoma (RCC) in response to RE treatment has never been reported. To understand the potential anticancer effect of RE on RCC at molecular level, we profiled and analyzed the expression of 2059 cancer-related genes in a RCC cell line RCC54 treated with RE. Biological functions of 633 genes were annotated based on biological process ontology and clustered into functional categories. Twenty-nine highly differentially expressed genes in RE treated RCC54 were identified and the potential implications of some gene expression alterations in RCC carcinogenesis were identified. RE was also shown to inhibit cell growth and induce cell death of RCC cells. The expression alterations of selected genes were validated using reverse transcription polymerase chain reaction. In addition, the gene expression profiles under different RE treatments were analyzed and visualized using singular value decomposition. The findings from this study support the hypothesis that RE induces differential expression of genes that are directly or indirectly related to the inhibition of RCC cell growth and induction of RCC cell death. In addition, it is apparent that the gene expression alterations due to RE treatment depend strongly on RE concentration. This study provides a general understanding of the overall genetic response of RCC54 to RE treatment and yields insights into the understanding of the cancer preventive mechanism of RE in RCC.

Angiogenesis Inhibitors↗

PubMed2004

Microarray gene expression profiling and analysis in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. METHODS: Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. RESULTS: Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR). Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. CONCLUSIONS: This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most notably, genes involved in cell adhesion were dominantly up-regulated whereas genes involved in transport were dominantly down-regulated. This study reveals significant gene expression alterations in key biological pathways and provides potential insights into understanding the molecular mechanism of renal cell carcinogenesis.

Adenocarcinoma, Clear Cell↗

PubMed2004

Differential protein profiling in renal-cell carcinoma.

Characterizing the alterations of protein expression in cancer cells can be very useful in providing insight into the changes in the functional pathways and thus the fundamental mechanisms of cancer development at the molecular level. In this study, we profiled protein expressions in eleven pairs of primary cell cultures derived from renal-cell carcinoma (RCC) tissues and patient-matched normal kidney tissues utilizing two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Together with the immunoblot analysis of proteins from the RCC tissues, the study also demonstrated that the alterations of protein expression observed in RCC primary cell cultures reflected those observed in the original RCC tissues. We analyzed the expression profiles and identified proteins differentially expressed in RCC primary cell cultures by 2-D PAGE and mass spectrometry (MS). We found sixteen proteins were overexpressed and seven proteins underexpressed in RCC. The deregulated expressions of proteins include those involved in metabolism, cellular morphology, heat shock response, cell growth, etc. Overexpression of three proteins, alphabeta-crystallin, manganese superoxide dismutase (MnSOD), and annexin IV, most commonly observed in primary RCC cell cultures, were also observed by immunoblot analysis of proteins from the RCC tissues from which the primary cell cultures were derived. Semi-quantitative reverse transcription (RT)-polymerase chain reaction (PCR) analysis revealed the direct correlation between deregulated gene expression and the corresponding protein abundance in two of the three most commonly upregulated proteins we found in RCC.

Annexin A4↗