• Title/Summary/Keyword: MafK

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Putative Association of ITGB1 Haplotype with the Clearance of HBV Infection

  • Park, Tae-Joon;Chun, Ji-Yong;Bae, Joon-Seol;Kim, Ja-Son Y.;Lee, Jin-Sol;Pasaje, Charisse Flerida;Park, Byung-Lae;Cheong, Hyun-Sub;Lee, Hyo-Suk;Kim, Yoon-Jun;Shin, Hyoung-Doo
    • Genomics & Informatics
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    • v.8 no.1
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    • pp.9-18
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    • 2010
  • Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (${\beta}1$) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and $P^{corr}=0.05$). The minor allele frequency (MAF) of ITGB1 haplotype -2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.

Bioinformatic Prediction of SNPs within miRNA Binding Sites of Inflammatory Genes Associated with Gastric Cancer

  • Song, Chuan-Qing;Zhang, Jun-Hui;Shi, Jia-Chen;Cao, Xiao-Qin;Song, Chun-Hua;Hassan, Adil;Wang, Peng;Dai, Li-Ping;Zhang, Jian-Ying;Wang, Kai-Juan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.937-943
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    • 2014
  • Polymorphisms in miRNA binding sites have been shown to affect miRNA binding to target genes, resulting in differential mRNA and protein expression and susceptibility to common diseases. Our purpose was to predict SNPs (single nucleotide polymorphisms) within miRNA binding sites of inflammatory genes in relation to gastric cancer. A complete list of SNPs in the 3'UTR regions of all inflammatory genes associated with gastric cancer was obtained from Pubmed. miRNA target prediction databases (MirSNP, Targetscan Human 6.2, PolymiRTS 3.0, miRNASNP 2.0, and Patrocles) were used to predict miRNA target sites. There were 99 SNPs with MAF>0.05 within the miRNA binding sites of 41 genes among 72 inflammation-related genes associated with gastric cancer. NF-${\kappa}B$ and JAK-STAT are the two most important signaling pathways. 47 SNPs of 25 genes with 95 miRNAs were predicted. CCL2 and IL1F5 were found to be the shared target genes of hsa-miRNA-624-3p. Bioinformatic methods could identify a set of SNPs within miRNA binding sites of inflammatory genes, and provide data and direction for subsequent functional verification research.

Comprehensive Bioinformation Analysis of the MRNA Profile of Fascin Knockdown in Esophageal Squamous Cell Carcinoma

  • Wu, Bing-Li;Luo, Lie-Wei;Li, Chun-Quan;Xie, Jian-Jun;Du, Ze-Peng;Wu, Jian-Yi;Zhang, Pi-Xian;Xu, Li-Yan;Li, En-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7221-7227
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    • 2013
  • Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers, is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC). Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC. Method: In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown were analyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin. Results: Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

Bach2 represses the AP-1-driven induction of interleukin-2 gene transcription in CD4+ T cells

  • Jang, Eunkyeong;Lee, Hye Rim;Lee, Geon Hee;Oh, Ah-Reum;Cha, Ji-Young;Igarashi, Kazuhiko;Youn, Jeehee
    • BMB Reports
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    • v.50 no.9
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    • pp.472-477
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    • 2017
  • The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed $CD4^+$ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect. Luciferase and chromatin immunoprecipitation assays revealed that Bach2 binds to multiple Maf-recognition element-like sites on the interleukin-2 proximal promoter in a manner competitive with AP-1, and thereby represses AP-1-driven induction of interleukin-2 transcription. Thus, this study demonstrates that Bach2 is a direct repressor of the interleukin-2 gene in $CD4^+$ T cells during the immediate early phase of AP-driven activation, thereby playing an important role in the maintenance of immune quiescence in the steady state.

A Comparison of Two Kinds of Markers Applied in Analysis of Genetic Diversity in Sheep and Goat Populations

  • Yang, Z.P.;Chang, H.;Sun, W.;Gen, R.Q.;Mao, Y.J.;Tsunoda, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.7
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    • pp.892-896
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    • 2004
  • A genetic examination using 14 structural loci and 7 microsatellite markers was carried out among random samples of Hu sheep (Hu), Tong sheep (Tong) and Yantse River Delta White goat (YRD); The mean heterozygosity (H), mean polymorphism information contents (PIC) and mean effective numbers of alleles (Ne) calculated based on the data from the above two types of genetic markers were compared. The standard genetic distances among the three populations based on two types of gene frequencies were calculated and compared. The results show that the mean heterozygosity (H), mean polymorphism information contents (PIC) and mean effective numbers of alleles (Ne) based on 7 microsatellite markers are greater than those based on the structural loci. The standard genetic distances based on structural loci among the three populations are: 0.0268-0.2487, the standard genetic distances based on microsatellite markers are: 0.2321-1.2313. The study indicates that structural and microsatellite markers reflect the genetic variation of the three populations consistently: Tong>Hu>YRD. The differentiation between related species or interpopulations can be expressed more effectively by microsatellite markers than structural markers. Oar FCB11, MAF33, Oar AE101, Oar FCB128 and OarFCB304 can be used as representative loci for research on genetic differentiation between sheep and goat.

Microarray Analysis of Gene Expression in Raw 264.7 Cells Treated with Hominis Placenta Herbal-Acupuncture Solution (자하거(紫河車) 약침액(藥鍼液)이 Lipopolysaccharide로 처리된 RAW 264.7 대식세포주(大食細胞柱)의 유전자(遺傳子) 발현(發顯)에 미치는 영향(影響))

  • Jang, Hyun-Seok;Lee, Kyung-Min;Lim, Sung-Chul;Eom, Dong-Myung;Seo, Jung-Chul
    • Korean Journal of Oriental Medicine
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    • v.12 no.3 s.18
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    • pp.131-141
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    • 2006
  • Hominis Placenta has a broad array of clinical applications in Korean medicine, including treatment of inflammatory conditions such as rheumatoid arthritis. The purpose of this study is to explore the global gene expression profiles in human RAW 264.7 cell lines treated with Hominis Placenta herbal-acupuncture solution (HPHAS) using microarray analysis. The RAW 264.7 cells were treated with lipopolysaccharide (LPS), HPHAS, or both. Of the 8,170 genes profiled in this study, with a cut-off level of two-fold change in the expression, 72 genes (CTD1, regulating synaptic membrane exocytosis 2, etc.) were upregulated and 135 genes(splicing factor, arginine/serine-rich 1, actinin, alpha 1, etc.) downregulated following LPS treatment. One gene (acrosin) was upregulated and 12 genes (phospholipase A2, group IB, neurofilament, heavy polypeptide 200kDa, etc.) were downregulated following HPHAS treatment. Eleven genes (RAB27A, member RAS oncogene family, eosinophil peroxidase, etc.) were upregulated and 16 genes (V-maf musculoaponeurotic fibrosarcoma oncogene homolog G (avian), RW1 protein, etc.) were downregulated following co-stimulation of HPHAS and LPS. It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacological actions of HPHAS in the treatment of arthritis. Further studies, however, are required to concretely prove the effectiveness of HPHAS.

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Effect of Atractylodis Rhizoma Alba on Osteoclast Formation (백출의 파골세포 분화에 미치는 영향)

  • Park, Sung-Tae;Lee, Myeung-Su;Jeon, Byung-Hun;Park, Kie-In;Oh, Jae-Min
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.1
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    • pp.109-114
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    • 2011
  • Atractylodis Rhizoma Alba is commonly used herbal medicine and it has been known that has immuno-regualtory effects and anti-cancer effects. The inhibition of osteoclastogenesis is essential for the prevention and treatment of osteoporosis. The aim of this study was to evaluate the effects of Atractylodis Rhizoma Alba on osteoclast differentiation in vitro and on resorbing activity of osteoclast. Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of Atractylodis Rhizoma Alba. The expression of c-fos, tartrate-resistant acid phosphatase (TRAP), OSCAR, DC-STAMP, cathepsin K, MafB and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of TNF receptor-associated factor-6 (TRAF-6), c-fos and NFATc1 protein were assessed by Western blot analysis. Also the correlation with MAPKs and NF-${\kappa}B$ pathways were measured by using Western blot analysis. With bone resorption study, I tried to evaluate the inhibitory effects of Atractylodis Rhizoma Alba on mature osteoclast function. Atractylodis Rhizoma Alba inhibited the RANKL induced osteoclastic differentiation from bone marrow macrophage in a dose dependant manner without cellular toxicity. Gene expression of c-fos and NFATc1 was significantly down regulated with Atractylodis Rhizoma Alba treatment. Atractylodis Rhizoma Alba markedly inhibited the RANKL-induced osteoclastogenesis through suppression of nuclear factor kappa b (NF-${\kappa}B$) pathway, down stream pathway of p38, ERK and JNK pathway. Taken together, I concluded that Atractylodis Rhizoma Alba have beneficial effect on osteoporosis by inhibition of osteoclast differentiation and by inhibition of functioning osteoclast. Thus I expect that Atractylodis Rhizoma Alba could be a treatment option for osteoporosis.

Identification of Genomic Differences between Hanwoo and Holstein Breeds Using the Illumina Bovine SNP50 BeadChip

  • Melka, Hailu Dadi;Jeon, Eun-Kyeong;Kim, Sang-Wook;Han, James-Bond;Yoon, Du-Hak;Kim, Kwan-Suk
    • Genomics & Informatics
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    • v.9 no.2
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    • pp.69-73
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    • 2011
  • The use of genomic information in genomic selection programs for dairy and beef cattle breeds has become a reality in recent years. In this investigation, we analyzed single-nucleotide polymorphisms (SNPs) for Hanwoo (n=50) and Holstein (n=50) breeds using the Illumina Bovine SNP50 BeadChip to facilitate genomic selection and utilization of the Hanwoo breed in Korea. Analysis of the entire genomes showed different spectra of SNP frequencies for Hanwoo and Holstein cattle. The study revealed a highly significant (p<0.001) difference between Hanwoo and Holstein cattle in minor allele frequency (MAF). The average MAFs were $0.19{\pm}0.16$ and $0.22{\pm}0.16$ for Hanwoo and Holstein, respectively. From the total of 52,337 SNPs that were successfully identified, about 72% and 79% were polymorphic in Hanwoos and Holsteins, respectively. Polymorphic and fixed SNPs were not distributed uniformly across the chromosomes within breeds or between the two breeds. The number of fixed SNPs on all chromosomes was higher in Hanwoo cattle, reflecting the genetic uniqueness of the Hanwoo breed. In general, the rate of polymorphisms detected in these two breeds suggests that the SNPs can be used for different applications, such as whole-genome association and comparative genetic studies, and are a helpful tool in developing breed identification genetic markers.

Embryological Characteristics on Seed Sterility of Ligusticum chuanxiong Hoit. (천궁의 종자불임에 관한 발생학적 특성)

  • Park, Chung-Heon;Lee, Man-Sang;Namkoong, Seung-Bak;Yu, Hong-Seob;Park, Hee-Woon
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.3
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    • pp.209-213
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    • 2004
  • Ligusticum chuanxiong is receiving much attentions as one of the important medicinal crops with the increasement of the crude drug demands. This study was conducted to obtain the basic informations of breeding of Ligusticum chuanxiong. Embryological characteristics were examined to elucidate the process of male and female gametophytic development and fertilization. Meiosis and nucleus division of megaspore and microspore were proceeded normally. With regard to the formation of female gametophyte, only a half of female gametophyte developed to normal egg apparatus. While another 50% showed abnormal egg apparatus with poly-nuclei or non-nuclei ovule. The pollens developed from the micros pore were formed more than 90 % of normal pollen. It was difficult to observe fertilization because ovule tissue was very compact and cell was extremely tiny, but could be easely observed proembryo and embryo formation. Only 30 percent developed into proembryo and subsequently into embryo, and the others were degenerated.

Histopathological observations and virus detection by in situ hybridization in wild rats intranasally infected with Aujeszky's disease virus isolated in Korea (국내분리 오제스키병 바이러스로 비강접종한 야생집쥐(Rattus norvegicus)의 병리학적 소견 및 in situ hybridization에 의한 바이러스 동정)

  • Song, Geun-seok;Moon, Oun-kyong;Jeong, Chang-geun;Kim, Soon-bok
    • Korean Journal of Veterinary Research
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    • v.39 no.3
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    • pp.531-537
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    • 1999
  • The present study was carried out to investigate the pathogenicity and pathogenesis of wild rats(Rattus norvegicus), trapped in nature, intranasally infected with Aujeszky's disease virus(ADV/NYJ-1-87) by histopathology, immunohistochemistry and in situ hybridization(ISH). Fifteen rats inoculated intranasally were roughened haircoat, anorexia, listlessness, and depression second day after inoculation, and three rats died in 66-72 hours. Eight rats showed severe pruritus at the face that was accompanied by frequent face-washing movements of the forelegs, and then became violent and spasmodic for an hour or until they died. Four rats slowly recovered after showing mild clinical signs of the disease. Microscopic lesions in infected rats were characterized by meningitis, perivascular round cell infiltration, focal gliosis, and neuronal degeneration and necrosis. And intranuclear inclusion bodies were frequently detected in the cerebral cortex and medulla. Positive reaction to ADV by immunohistochemistry and ISH were detected in the following areas : trigermimal ganglion, brain, tonsil, nasal mucosa, spleen, lung and liver. The result has suggested that ADV intranasally infected in wild rats is followed by replication in epithelial calls of nasal mucosa and tonsil, then invade local lymph nodes by way of the lymphatics. It is also believed that the virus invades bipolar olfactory cells and trigerminal ganglion; and then spread into central nervous system.

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