• Title/Summary/Keyword: pathway database

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GATA2-Mediated Transcriptional Activation of Notch3 Promotes Pancreatic Cancer Liver Metastasis

  • Lin, Heng;Hu Peng;Zhang, Hongyu;Deng, Yong;Yang, Zhiqing;Zhang, Leida
    • Molecules and Cells
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    • v.45 no.5
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    • pp.329-342
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    • 2022
  • The liver is the predominant metastatic site for pancreatic cancer. However, the factors that determine the liver metastasis and the specific molecular mechanisms are still unclear. In this study, we used human pancreatic cancer cell line Hs766T to establish Hs766T-L3, a subline of Hs766T with stable liver metastatic ability. We performed RNA sequencing of Hs766T-L3 and its parental cell line Hs766T, and revealed huge differences in gene expression patterns and pathway activation between these two cell lines. We correlated the difference in pathway activation with the expression of the four core transcriptional factors including STAT1, NR2F2, GATA2, and SMAD4. Using the TCGA database, we examined the relative expression of these transcription factors (TFs) in pan-cancer and their relationship with the prognosis of the pancreatic cancer. Among these TFs, we considered GATA2 is closely involved in tumor metastasis and may serve as a potential metastatic driver. Further in vitro and in vivo experiments confirmed that GATA2-mediated transcriptional activation of Notch3 promotes the liver metastasis of Hs766T-L3, and knockdown of either GATA2 or Notch3 reduces the metastatic ability of Hs766T-L3. Therefore, we claim that GATA2 may serve as a metastatic driver of pancreatic cancer and a potential therapeutic target to treat liver metastasis of pancreatic cancer.

Analysis of the Active Compounds and Therapeutic Mechanisms of Yijin-tang on Meniere's Disease Using Network Pharmacology(II) (네트워크 약리학을 활용한 메니에르병에 대한 이진탕(二陳湯)의 활성 성분과 치료 기전 연구(II))

  • SunKyung Jin;HaeJeong Nam
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.36 no.2
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    • pp.1-9
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    • 2023
  • Objectives : This study used a network pharmacology approach to analyze the treatment mechanisms of Yijin-tang on Meniere's disease, and comparative analysis the treatment mechanisms of drugs recommended in the Meniere's disease treatment guidelines. Methods : We collected information on the recommended drugs from the Meniere's disease treatment guidelines and their target proteins were screened via the STITCH database. The intersection targets were obtained through Venny 2.1.0. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed using ClueGO. Results : The 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were associated with both Yijin-tang and Meniere's disease related genes. The 10 proteins(AQP2, KCNE1, AQP1, AVP, ACE, HRH1, HRH3, NOS1, CA1, CFTR) were associated with both the recommended drugs in the guidelines and Meniere's disease related genes. The 2 proteins(CFTR, NOS1) were common across all three groups. Further, GO/KEGG pathway analysis of the collected proteins revealed that the common mechanisms of action between Yijin-tang and the recommended drugs in the guidelines were related to pathways involving immune dysfunction and disturbances in lymphatic fluid homeostasis. In addition, the recommended drugs in the guidelines appeared to act through mechanisms that improve blood flow through vasodilation. Conclusions : Pharmacological network analysis can help to explain the treatment mechanisms of Yijin-tang on Meniere's disease.

Characterization of a Potential Probiotic Lactiplantibacillus plantarum LRCC5310 by Comparative Genomic Analysis and its Vitamin B6 Production Ability

  • Yunjeong Lee;Nattira Jaikwang;Seong keun Kim;Jiseon Jeong;Ampaitip Sukhoom;Jong-Hwa Kim;Wonyong Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.5
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    • pp.644-655
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    • 2023
  • Safety assessment and functional analysis of probiotic candidates are important for their industrial applications. Lactiplantibacillus plantarum is one of the most widely recognized probiotic strains. In this study we aimed to determine the functional genes of L. plantarum LRCC5310, isolated from kimchi, using next-generation, whole-genome sequencing analysis. Genes were annotated using the Rapid Annotations using Subsystems Technology (RAST) server and the National Center for Biotechnology Information (NCBI) pipelines to establish the strain's probiotic potential. Phylogenetic analysis of L. plantarum LRCC5310 and related strains showed that LRCC5310 belonged to L. plantarum. However, comparative analysis revealed genetic differences between L. plantarum strains. Carbon metabolic pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database showed that L. plantarum LRCC5310 is a homofermentative bacterium. Furthermore, gene annotation results indicated that the L. plantarum LRCC5310 genome encodes an almost complete vitamin B6 biosynthetic pathway. Among five L. plantarum strains, including L. plantarum ATCC 14917T , L. plantarum LRCC5310 detected the highest concentration of pyridoxal 5'-phosphate with 88.08 ± 0.67 nM in MRS broth. These results indicated that L. plantarum LRCC5310 could be used as a functional probiotic for vitamin B6 supplementation.

Network pharmacology and molecular docking reveal the mechanism of Qinghua Xiaoyong Formula in Crohn's disease

  • Chenyang Fang;Yanni Pei;Yunhua Peng;Hong Lu;Yin Qu;Chunsheng Luo;Yafeng Lu;Wei Yang
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.365-374
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    • 2023
  • Crohn's disease (CD) is a chronic inflammatory illness of the digestive system with unknown etiology, and its incidence is increasing worldwide. However, there are currently no effective treatments or medications available for individuals with CD. Therefore, novel therapeutic strategies are urgently needed. The bioactive compounds and targets associated with compounds of Qinghua Xiaoyong Formula (QHXYF) were examined using The Traditional Chinese Medicine Systems Pharmacology database, and 5 disease target databases were also used to identify CD-related disease targets. A total of 166 overlapping targets were identified from QHXYF-related and CD-related disease targets and they were found to be enriched in oxidative stress-related pathways and the PI3K/AKT signaling pathway. Molecular docking was then used to predict how the bioactive compounds would bind to the hub targets. It was found that quercetin could be the core bioactive compound and had good binding affinity to the top 5 hub targets. Finally, animal experiments were performed to further validate the findings, and the results revealed that QHXYF or quercetin inhibited 2,4,6-trinitrobenzenesulfonic acid-induced inflammation and oxidative stress processes by inhibiting the PI3K/AKT pathway, thereby improving CD symptoms. These findings suggest that QHXYF and quercetin may be potential novel treatments for CD.

Expression of anoctamin 7 (ANO7) is associated with poor prognosis and mucin 2 (MUC2) in colon adenocarcinoma: a study based on TCGA data

  • Chen, Chen;Siripat Aluksanasuwan;Keerakarn Somsuan
    • Genomics & Informatics
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    • v.21 no.4
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    • pp.46.1-46.10
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    • 2023
  • Colon adenocarcinoma (COAD) is the predominant type of colorectal cancer. Early diagnosis and treatment can significantly improve the prognosis of COAD patients. Anoctamin 7 (ANO7), an anion channel protein, has been implicated in prostate cancer and other types of cancer. In this study, we analyzed the expression of ANO7 and its correlation with clinicopathological characteristics among COAD patients using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the University of Alabama at Birmingham CANcer (UALCAN) databases. The GEPIA2, Kaplan-Meier plotter, and the Survival Genie platform were employed for survival analysis. The co-expression network and potential function of ANO7 in COAD were analyzed using GeneFriends, the Database for Annotation, Visualization and Integrated Discovery (DAVID), GeneMANIA, and Pathway Studio. Our data analysis revealed a significant reduction in ANO7 expression levels within COAD tissues compared to normal tissues. Additionally, ANO7 expression was found to be associated with race and histological subtype. The COAD patients exhibiting low ANO7 expression had lower survival rates compared to those with high ANO7 expression. The genes correlated with ANO7 were significantly enriched in proteolysis and mucin type O-glycan biosynthesis pathway. Furthermore, ANO7 demonstrated a direct interaction and a positive co-expression correlation with mucin 2 (MUC2). In conclusion, our findings suggest that ANO7 might serve as a potential prognostic biomarker and potentially plays a role in proteolysis and mucin biosynthesis in the context of COAD.

Pedigree Analysis of 17 High Quality Korean Rice Cultivars Using Web Database Systems

  • Yi, Gi-Hwan;Park, Dong-Soo;Chung, Eun-Sook;Song, Song-Yi;Jeon, Nam-Soo;Nam, Min-Hee;Kim, Doh-Hoon;Han, Chang-Deok;Eun, Moo-Young;Ku, Yeon-Chung
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.51 no.6
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    • pp.554-564
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    • 2006
  • It is important to understand pedigree of rice cultivars commonly used for breeding. In this paper, pedigree tables for tracking the pedigree of 17 representative rice cultivars recommended by Rural development Adminstration (RDA) were completed and analyzed using two kinds of web database system; 'IRIS' and 'RRDB'. Seven cultivars, namely, 'Sangmibyeo', 'Ilpumbyeo', 'Saegewhabyeo', 'Surabyeo', 'Shindongjinbyeo', 'Ilmibyeo' and 'Jungwhabyeo' had 'Koshihikari' on the pedigree of their ancestor. Besides 'Koshihikari', the most feguently used ancestral germplasms among the high quality rice cultivars were 'Fujisaka 5', 'Kameno o' and 'Asahi', 'Fujisaka 5' was used as ancestral parent in 12 out of 17 cultivars. Interestingly, 'Kameno o' was used in pedigree of 16 out of 17 high quality varieties and 'Asahi' was used in the ancestral pedigree of all 17 varieties. 'Hwayeongbyeo' was used as one of parent in the breeding of 'Dongjin 1', 'Hwabongbyeo', 'Saegewhabyeo' and 'Junambyeo'. 'Ilpumbyeo' was used in the breeding pathway of 'Junambyeo' and 'Saegewhabyeo', 'Mangeumbyeo' itself was not enlisted as one of high quality rice cultivars, but was used as a breeding parent of three high quality varieties, namely, 'Saegewhabyeo', 'Hwabongbyeo' and 'Nampyeongbyeo'. Incorporated with evaluation data, pedigree will provide a valuable chance to genealogical tracking of agronomic traits such as disease resistance, grain quality and etc.

A Study on Clustering and Identifying Gene Sequences using Suffix Tree Clustering Method and BLAST (서픽스트리 클러스터링 방법과 블라스트를 통합한 유전자 서열의 클러스터링과 기능검색에 관한 연구)

  • Han, Sang-Il;Lee, Sung-Gun;Kim, Kyung-Hoon;Lee, Ju-Yeong;Kim, Young-Han;Hwang, Kyu-Suk
    • Journal of Institute of Control, Robotics and Systems
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    • v.11 no.10
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    • pp.851-856
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    • 2005
  • The DNA and protein data of diverse species have been daily discovered and deposited in the public archives according to each established format. Database systems in the public archives provide not only an easy-to-use, flexible interface to the public, but also in silico analysis tools of unidentified sequence data. Of such in silico analysis tools, multiple sequence alignment [1] methods relying on pairwise alignment and Smith-Waterman algorithm [2] enable us to identify unknown DNA, protein sequences or phylogenetic relation among several species. However, in the existing multiple alignment method as the number of sequences increases, the runtime increases exponentially. In order to remedy this problem, we adopted a parallel processing suffix tree algorithm that is able to search for common subsequences at one time without pairwise alignment. Also, the cross-matching subsequences triggering inexact-matching among the searched common subsequences might be produced. So, the cross-matching masking process was suggested in this paper. To identify the function of the clusters generated by suffix tree clustering, BLAST was combined with a clustering tool. Our clustering and annotating tool is summarized as the following steps: (1) construction of suffix tree; (2) masking of cross-matching pairs; (3) clustering of gene sequences and (4) annotating gene clusters by BLAST search. The system was successfully evaluated with 22 gene sequences in the pyrubate pathway of bacteria, clustering 7 clusters and finding out representative common subsequences of each cluster

Homology of Scytalone Dehydratase Melanin Gene in Venturia nashicola (배검은별무늬병균의 Scytalone Dehydratase 멜라닌유전자의 상동성)

  • Yun, Yeo Hong;Yoon, Seong Kwon;Son, Seung Yeol;Kim, Seong Hwan
    • The Korean Journal of Mycology
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    • v.41 no.3
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    • pp.200-204
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    • 2013
  • Dihydroxynaphthalene (DHN) melanin is known to be present in some ascomycete fungi. To verify the type of melanin in Venturia nashicola that cause scab on pear, we investigated scytalone dehydratase (SD) gene, one of DHN melanin genes, from 11 isolates of V. nashicola from different provinces in Korea and Japan. Through PCR approach, 429 bp amplicon was produced from the 11 isolates and sequenced. All of the PCR-amplified sequences were determined as SD gene through GenBank database search. All the determined sequences were composed of an intron and two exons coding for 122 amino acids of SD. The homology of SD gene was 100% among the 11 isolates. Sequence identity of the predicted SD protein of 122 amino acids ranged 69 to 73% with other fungi. Our results proved that V. nashicola operates DHN melanin pathway.

CDRgator: An Integrative Navigator of Cancer Drug Resistance Gene Signatures

  • Jang, Su-Kyeong;Yoon, Byung-Ha;Kang, Seung Min;Yoon, Yeo-Gha;Kim, Seon-Young;Kim, Wankyu
    • Molecules and Cells
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    • v.42 no.3
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    • pp.237-244
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    • 2019
  • Understanding the mechanisms of cancer drug resistance is a critical challenge in cancer therapy. For many cancer drugs, various resistance mechanisms have been identified such as target alteration, alternative signaling pathways, epithelial-mesenchymal transition, and epigenetic modulation. Resistance may arise via multiple mechanisms even for a single drug, making it necessary to investigate multiple independent models for comprehensive understanding and therapeutic application. In particular, we hypothesize that different resistance processes result in distinct gene expression changes. Here, we present a web-based database, CDRgator (Cancer Drug Resistance navigator) for comparative analysis of gene expression signatures of cancer drug resistance. Resistance signatures were extracted from two different types of datasets. First, resistance signatures were extracted from transcriptomic profiles of cancer cells or patient samples and their resistance-induced counterparts for >30 cancer drugs. Second, drug resistance group signatures were also extracted from two large-scale drug sensitivity datasets representing ~1,000 cancer cell lines. All the datasets are available for download, and are conveniently accessible based on drug class and cancer type, along with analytic features such as clustering analysis, multidimensional scaling, and pathway analysis. CDRgator allows meta-analysis of independent resistance models for more comprehensive understanding of drug-resistance mechanisms that is difficult to accomplish with individual datasets alone (database URL: http://cdrgator.ewha.ac.kr).

Bioinformatic analyses reveal the prognostic significance and potential role of ankyrin 3 (ANK3) in kidney renal clear cell carcinoma

  • Keerakarn Somsuan;Siripat Aluksanasuwan
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.22.1-22.15
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    • 2023
  • Kidney renal clear cell carcinoma (KIRC) is one of the most aggressive cancer type of the urinary system. Metastatic KIRC patients have poor prognosis and limited therapeutic options. Ankyrin 3 (ANK3) is a scaffold protein that plays important roles in maintaining physiological function of the kidney and its alteration is implicated in many cancers. In this study, we investigated differential expression of ANK3 in KIRC using GEPIA2, UALCAN, and HPA databases. Survival analysis was performed by GEPIA2, Kaplan-Meier plotter, and OS-kirc databases. Genetic alterations of ANK3 in KIRC were assessed using cBioPortal database. Interaction network and functional enrichment analyses of ANK3-correlated genes in KIRC were performed using GeneMANIA and Shiny GO, respectively. Finally, the TIMER2.0 database was used to assess correlation between ANK3 expression and immune infiltration in KIRC. We found that ANK3 expression was significantly decreased in KIRC compared to normal tissues. The KIRC patients with low ANK3 expression had poorer survival outcomes than those with high ANK3 expression. ANK3 mutations were found in 2.4% of KIRC patients and were frequently co-mutated with several genes with a prognostic significance. ANK3-correlated genes were significantly enriched in various biological processes, mainly involved in peroxisome proliferator-activated receptor (PPAR) signaling pathway, in which positive correlations of ANK3 with PPARA and PPARG expressions were confirmed. Expression of ANK3 in KIRC was significantly correlated with infiltration level of B cell, CD8+ T cell, macrophage, and neutrophil. These findings suggested that ANK3 could serve as a prognostic biomarker and promising therapeutic target for KIRC.