Biomedical subjects

Chen Tan

Publications and source records attributed to Chen Tan.

14 recordsLinked to original sources

PubMed2026

Genome assembly and subgenomic interactions in Brassica napus additional lines with an alien B05 chromosome from B. juncea.

Alien chromosome addition lines hold significant value for breeding and genetic research. However, the genetic interaction between the recipient genome(s) and the alien chromosomes remain largely unclear. Here, we analyzed the genomic composition and gene expression of two purple-leaved B. napus alien addition lines carrying chromosome B05 from B. juncea: the monosomic line ZYCB3 (MAAL, 2n = 39, AACC + 1B05) and the disomic line ZY52 (DAAL, 2n = 40, AACC + 2B05). We assembled a chromosome-level genome of the DAAL ZY52 disomic line and characterized its genomic variation and chromosome introgression patterns. In addition to chromosome B05, multiple introgressed fragments derived from the donor B. juncea line ZYJC were identified, revealing extensive genome remodeling during distant hybridization and backcross breeding. We then used multi-omics approaches to explore chromosomal interactions and the regulation of anthocyanin biosynthesis. Notably, the addition of chromosome B05 was associated with stronger repression of homoeologous genes on C-subgenome chromosomes than on A-subgenome chromosomes. In ZY52, homoeologous genes on chromosome C01 showed reduced expression, whereas in the ZYCB3 monosomic line reduced expression was observed on both C01 and C02. Comparative transcriptomic and metabolomic analyses further showed that highly expressed anthocyanin biosynthesis genes (ABGs) on chromosome B05contributed to anthocyanin accumulation and the purple-leaf phenotype in both addition lines. Overall, this study provides new insights into interchromosomal interactions, genome remodeling, and phenotypic variation in alien addition lines.

Journal Article↗

PubMed2006

The single nucleotide polymorphisms of I(Ks) potassium channel genes and their association with atrial fibrillation in a Chinese population.

Recent studies suggest that genetic mutation of the slow delayed rectifier potassium channel (I(Ks)) may underlie atrial fibrillation (AF). We investigated the association between AF and the single nucleotide polymorphisms (SNPs) of genes KCNQ1, KCNE1 and KCNE4 associated with this channel. Common non-synonymous SNPs in KCNQ1 and KCNE1 known to be frequent in Asian people were selected and direct sequencing of KCNE4 was performed to identify possible SNPs. The AF group consisted of 142 hospitalized patients with AF, the community control group consisted of 120 subjects, and a ward control group consisted of 118 hospitalized patients without AF. Restriction fragment length polymorphism analysis was performed to determine the genotypes. The minor allele frequencies of P448R, R519H, G643S for KCNQ1 and G38S and D85N for KCNE1 in the AF group, the community control group and the ward control group were 9.9, 7.9, 9.3%; 0, 0, -; 4.3, 4.2, 1.7%; 28.4, 31.7, 29.7%; 0.7, 0.4%, -, respectively. There was no significant association between these SNPs and AF phenotype. There were eight SNPs in the whole length of KCNE4 plus 1,000 bases upstream of this gene including the non-synonymous SNP E145D. Logistical regression analysis revealed a difference in the distribution of KCNE4 E145D in the AF and the community control group (minor allele frequency was 34.0 versus 27.1% respectively, OR = 1.66, p = 0.044). We provided the frequencies of non-synonymous SNPs of KCNQ1 and KCNE1 in Chinese population; none of these SNPs was associated with AF. But KCNE4 E145D may be associated with the AF phenotype.

Aged↗

PubMed2006

Differential expression of Epstein-Barr virus-encoded RNA and several tumor-related genes in various types of nasopharyngeal epithelial lesions and nasopharyngeal carcinoma using tissue microarray analysis.

Studies have revealed that Epstein-Barr virus (EBV) infection, genetic aberration, and environmental factors are of importance in the development of nasopharyngeal carcinoma (NPC), although the definite mechanism remains to be fully elucidated. The aim of our study is to investigate using tissue microarray analysis whether differential expression of EBV-encoded small RNA-1 (EBER-1) and several tumor-related genes were associated with NPC carcinogenesis. Immunohistochemistry and in situ hybridization were performed on tissue microarrays containing 148 NPCs and 164 noncancerous nasopharyngeal epithelia (NPE) with different morphologic features. We found that overexpressions of EBER-1 hybridization signals, p53, p21ras, and bcl-2 proteins and loss expressions of p16 and p27 proteins were significantly increased in NPC tissues compared with normal NPE and hyperplastic NPE (P </= .001). The overexpressions of EBER-1 and p53 (P < .001) and the loss expressions of P16 (P < .001) and P27 (P = .005) were also significantly higher and more frequently observed in NPC than in dysplastic NPE. The positive expression of EBER-1 hybridization signals in NPC had significant associations with overexpressions of p53 (P < .001), p21ras (P = .041), and bcl-2 proteins (P < .001) and loss expression of p16 protein (P = .001). Further analysis confirmed that the abnormal expression of p53, p16, and p27 proteins occurred in the earliest stage of nasopharyngeal epithelial carcinogenesis. In the final logistic regression analysis model, the positive hybridization signals of EBER-1 and the abnormal expression of p53, p16, and p27 proteins were independent contributions for nasopharyngeal carcinogenesis, and EBER-1 was the most significant, independent predictor of nasopharyngeal carcinogenesis (hazard ratio = 13.412, 95% confidence interval 6.179-29.111, P < .001). In conclusion, EBV infection, together with overexpressions of p53, and loss expressions of p16 and p27 proteins are involved in the multistep process of human nasopharyngeal epithelial carcinogenesis.

Adenocarcinoma↗

PubMed2005

NGX6 gene inhibits cell proliferation and plays a negative role in EGFR pathway in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in other parts of the world. A novel NPC-related gene was isolated by location candidate cloning strategy, whose expression was down-regulated in NPC. This gene was designated human NGX6 (Genbank accession AF188239) and encoded a predicted protein of 338 amino acids that harbors an EGF-like domain. The effects of NGX6 on cells from human NPC cell line HNE1 were investigated. The cells transfected with NGX6 had a markedly high expression of NGX6, leading to significant decrease in cell proliferation and the capability to form colonies in soft agar, delaying the G0-G1 cell cycle progression. Flow cytometry assay indicated that the expression of cyclin D1 significantly decreased in NGX6-transfected HNE1 cells as well as cyclin A and E. There was a delay in tumor formation and a dramatic reduction in tumor size when cells transfected with NGX6 were injected into nude mice. In another way, we found NGX6 played a negative role in EGFR Ras/Mek/MAPK pathway. We propose that NGX6, as an EGF-like domain gene, could delay cell cycle G0-G1 progression and thus inhibit cell proliferation by negatively regulating EGFR pathway in NPC cells and down-regulating the expression of cyclin D1 and E.

Animals↗

PubMed2005

[Function of a novel brain-specific gene LRRC4].

OBJECTIVE: To study the suppressive effect of LRRC4 gene on human glioma U251 cells and further investigate its biological functions. METHODS: H&E, DNA and AgNORs stainings were performed on LRRC4-transfected U251 cells, mock-transfected U251 cells and non-transfected U251 cells, respectively. Quantitative analysis including cell morphometry, DNA content, DNA ploidy, silver stained argyrophilic nucleolar organizer regions (AgNORs) were investigated by image analysis. Flow cytometry was employed to determine the difference of cell cycle distribution and MTT staining was used to elucidate the activity of the LRRC4-transfected U251 cells. RESULTS: The morphological cell parameters such as area, perimeter and diameter, DNA content, chromosomal aneupoloidy, mean area of AgNORs particles and mean nucleus area of the LRRC4-transfected U251 cells were remarkably decreased compared to those of the mock-transfected and non-transfected U251 cells (P < 0.05, P < 0.01). Meanwhile, significant accumulation of cells in G(0)/G(1) phase but decrease of cells in S and G(2)/M phase, was observed in transfected U251 cells compared to those of the mock-transfected and non-transfected U251 cells (P < 0.05, P < 0.01). MTT staining showed that proliferation activity of both the mock- and non-trasfected U251 cells was significantly higher than that of the U251 cells transfected with LRRC4 gene (P < 0.01). CONCLUSION: LRRC4 gene might be involved in tumor suppression by restraining DNA synthesis and the nucleoli organizer regions-associated proteins, keeping the cell cycles in phase G(0)/G(1) and reducing proliferation activity of the glioma cells. Morphometry combined with other techniques such as flow cytometry and MTT staining can well elucidate the biological function of novel genes.

Brain Neoplasms↗

PubMed2005

[The association of single nucleotide polymorphism of slow delayed rectifier K+ channel genes with atrial fibrillation in Han nationality Chinese].

OBJECTIVE: To investigate the association between atrial fibrillation and the single nucleotide polymorphism (SNP) of slow delayed rectifier K(+) channel (I(Ks)) genes in Han nationality Chinese. METHODS: Three hundred and eighty of Han nationality Chinese (142 atrial fibrillation, 120 in-hospital and 118 out-hospital control) were enrolled in this study. Asian specific non-synonymous SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were genotyped by restriction fragment length polymorphism analysis. A newly cloned KCNE4 gene was also screened for any possible SNP. RESULTS: The minor allele frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D was discovered and proven statistically to relation significantly to atrial fibrillation by logistic regression analysis (OR = 1.66, P = 0.044). The minor allele frequency of KCNE4 E145D was as high as 0.271 in out-hospital subjects. CONCLUSIONS: None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4 E145D may relation to atrial fibrillation. The effect of KCNE4 E145D variation on the function of I(Ks) channel is to be determined.

Aged↗

PubMed2004

Role of a novel EGF-like domain-containing gene NGX6 in cell adhesion modulation in nasopharyngeal carcinoma cells.

The epidermal growth factor (EGF)-like domain is involved in receptor-ligand interactions, extracellular matrix formation, cell adhesion and chemotaxis. Nasopharyngeal carcinoma associated gene 6 (NGX6) is a novel EGF-like domain-containing gene located at the high frequent loss of heterozygosity (LOH) region 9p21-22 associated with nasopharyngeal carcinoma (NPC). It is down-regulated in NPC and its over-expression can delay the cell cycle G(0)-G(1) progression in NPC cells. In the present study, in situ hybridization analysis, using NPC tissue microarrays, showed that loss of NGX6 expression was associated with NPC lymph node metastasis. The Tet-on gene expression system and cDNA array techniques were used to profile the potential targets of NGX6. We found that NGX6 can influence the expression of some cell adhesion molecules in NPC cells. NGX6 can associate with ezrin, a linkage between the cell membrane and cytoskeleton. The NGX6 protein was expressed on the cell surface as a glycoprotein. Ectopic induction of NGX6 can impair NPC cell migration and invasive ability as well as improve cell adhesion and gap junctional intercellular communication, and can suppress tumor formation in vivo. The data revealed that NGX6 plays a role in cell adhesion modulation in NPC cells.

Animals↗

PubMed2004

A susceptibility locus at chromosome 3p21 linked to familial nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. Chromosome translocation t(1;3) and frequent loss of heterogeneity on short arms of chromosome 3 and 9 have been reported to be associated with NPC, and a genome-wide scan identified an NPC susceptibility locus on chromosome 4p15.1-q12 recently. In our study, we collected samples from 18 families at high risk of NPC from the Hunan province in southern China, genotyped with a panel of polymorphic markers on short arms of chromosomes 3, 9, and 4p15.1-q12. A locus on 3p21 was identified to link to NPC with a maximum logarithm of odds for linkage score of 4.18. Fine mapping located the locus to a 13.6-cM region on 3p21.31-21.2, where a tumor suppressor gene cluster resided. Our findings identified a novel locus for NPC and provided a map location for susceptibility genes candidates. In contrast to a recent study, no significant evidence for NPC linkage to chromosomes 4 and 9 was observed.

China↗

PubMed2003

[Researching a novel NPC-related candidate suppressor gene BRD7 by two-dimensional gel electrophoresis and MALDI-TOF-MS].

BRD7 was isolated through cDNA representational difference analysis (RDA) (GenBank accession No. AF152604). Previous studies showed that BRD7 gene was down-regulated in nasopharyngeal carcinoma (NPC) cells and tissues, and three cSNPs (coding-region single nucleotide polymorphisms) were found on BRD7. In addition, six BRD7-interacting proteins were identified by yeast two-hybrid system. To study the function of this gene on carcinogenesis in NPC, BRD7 gene was transfected into HNE1 cells low-expressed BRD7 by using liposomes and a stable cell line over-expressing BRD7 was established. After two-dimensional gel electrophoresis(2-DE), twenty differentially expressed proteins were identified by MALDI-TOF-MS including argininosuccinate lyase, metalloproteinase inhibitor-2 precursor, proteaseome activator28 beta subunit, thyroid transcriptional factor-1, cyclinH (MO15-associated protein), and so on. These differentially expressed proteins are related to cell cycling, transcription regulation, signaling pathway etc. Therefore, BRD7 may exert its functions by mediating differential expression of these proteins.

Carrier Proteins↗

PubMed2003

Expression of LRRC4 has the potential to decrease the growth rate and tumorigenesis of glioblastoma cell line U251.

BACKGROUND & OBJECTIVE: LRRC4 is a novel gene that the author has identified recently, which displayed significant downregulation in primary brain tumor biopsies. This study was designed to investigate if LRRC4 has the potential of suppressing brain tumor growth. METHODS: The full-length coding region of LRRC4 gene was subcloned into the expression vector pcDNA3.1, the recombinant was introduced into the glioblastoma cell line U251 by liposome transfection, and the U251 cells stably expressing LRRC4 gene were established by G418 selection. Furthermore, cell proliferation assay, soft agar assay, tumorigenesis assay were taken to examine the effect of LRRC4 expression on cell growth and tumor formation. RESULTS: U251 cells stably expressing full-length coding region of LRRC4 were established by lipofection-mediated transfection and selected for further study. Compared with the nontransfected and vector-transfected cells, the cells transfected with LRRC4 cDNA exhibited a significant increase of expression of LRRC4 mRNA by Northern blot analysis. Further, when cell proliferation was followed over several days, the cells expressing the transfected LRRC4 cDNA grew more slowly than nontransfected cells. Consistently, the cells transfected with LRRC4 exhibited markedly lower colony formation rate. These clones were injected into athymic nude mice who was killed after 40 days and the tumor sizes were evaluated. Tumor volume in mice was significantly smaller in the group of cells stably transfected with LRRC4 cDNA than in the control. CONCLUSION: LRRC4 gene may be transfected into the human glioblastoma cell line U251. The expression of LRRC4 in U251 cells may have the potential to suppress tumor cell growth and the tumorigenesis of U251 cell transplanted in nude mice.

Animals↗

PubMed2002

Proteomic analysis of differential protein expression in human nasopharyngeal carcinoma cells induced by NAG7 transfection.

Nasopharyngeal carcinoma (NPC) is a commonly occurring tumor in southern China and south east Asia. A genetic factor has now been recognized to be associated with this cancer. A new gene, named NAG7, was cloned from the common minimal deletion region in 3p25.3-26.3. In order to investigate the function of NAG7 gene, proteomic methods were used to find and identify the differential proteins and expected to elucidate the mechanism of NAG7. The NAG7 eukaryotic expression vector was constructed and transfected into NPC cell line HNE1 with liposome. Twenty-two differential protein spots in transfected cells were found significant and reproducible using high-resolution two-dimensional electrophoresis. Nine proteins that were up-regulated and seven proteins that were down-regulated were identified by matrix assisted laser desorption/ionization time of flight mass spectrometry and database analysis. These proteins included growth arrest specific protein, DNA binding protein, caspase 6, pinch protein and ras-related protein rab-36, which are involved in cell cycling, transcription regulation, signaling pathways and apoptosis. NAG7 may exert its functions by mediating differential expression of these proteins.

Animals↗

PubMed2002

Effects of NPC-associated gene NAG7 on cell cycle and apoptosis in nasopharyngeal carcinoma cells.

BACKGROUND & OBJECTIVE: NPC-associated gene NAG7 was a novel candidate tumor suppressor gene associated with nasopharyngeal carcinoma cloned in our laboratory. This study was designed to investigate the potential effect of NAG7 on the cell cycle and apoptosis of nasopharyngeal carcinoma cell line HNE1 and its molecular mechanism. METHODS: NAG7 gene was introduced into HNE1 cells using lipofectin transfection technique. The expression level of NAG7 gene was analyzed by Northern blot. Cell cycle, cyclins, and cell apoptosis were detected by flow cytometry, and the expressions of cyclin D1 and cyclin E were detected by Western blot. RESULTS: NAG7 gene was re-expressed in NAG7 transfected HNE1 cells. Compared with HNE1 cells and vector transfected HNE1 cells, NAG7 transfected HNE1 cells arrested in G0/G1 phase increased (P < 0.05) and cells in S phase decreased (P < 0.05), the apoptosis cells increased (P < 0.05), and the levels of cyclins of A, B1, D1, and E decreased. Furthermore, the expression of cyclin D1 and E decreased in NAG7 transfected HNE1 cells. CONCLUSION: NAG7 gene re-expression could inhibit overproliferation of NPC cell by delaying the progression of G1 into S in cell cycle and inducing cell apoptosis.

Apoptosis↗

PubMed2002

[Specific suppression of GFP gene expression by short double stranded RNA in mammalian cells].

BACKGROUND AND OBJECTIVE: Double-stranded RNA (dsRNA) has been shown to interfere the function of specific genes in various species. The current study was designed to investigate whether short interfering RNAs(siRNAs) of green fluorescence protein(GFP) can inhibit the expression of GFP in mammalian cells. METHODS: HeLa cells were grown in standard conditions and transfected with pEGFPC2 and long dsRNA or siRNAs. Fluoroscopy and fluoroscent spectrophotometer were used to evaluate impact of GFPds RNA, Cx26 siRNAs, and longer double-strand RNAs on GFP expression, and flow cytometry was used to evaluate the cell apoptosis. RESULTS: Synthetic siRNAs can inhibite specific expression of GFP gene in human HeLa cell lines and siRNAs have no such specific effect. Longer double-stranded but no siRNAs can induce cell apoptosis. CONCLUSION: These observations may open a path toward the use of siRNAs as a new tool for researching gene function in mammalian cells and a gene-specific therapeutic tool.

Apoptosis↗

PubMed2001

Preliminary Function Study of NAG7 Using Two-dimensional Electrophoresis and Mass Spectrometry.

In search of mechanisms of function of NAG7 gene, a powerful new tool for the unambiguous characterization of gel-separated proteins is accomplished by the combination of mass spectrometry and sequence database searching. NAG7, a novel putative tumor suppressor gene, located on 3p25.3, was introduced into HNE1 cells by liposome transfection. We used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to identify proteins that were overexpressed in NAG7 transfected cells. After staining and image analysis, spots of interest were isolated and subjected to mass spectrometry (MS). We found nine proteins, which up-regulated in NAG7 transfected cells and be identified by MS. These proteins included growth arrest specific protein, DNA binding protein, c-myc promoter-binding protein and caspase 6 etc., which involved in cell cycling, transcription regulation, and apoptosis. NAG7 may exert the function by up-regulating the expression of these proteins.

Journal Article↗