• Title/Summary/Keyword: Resistant Genes

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3',4',5',5,7-Pentamethoxyflavone Sensitizes Cisplatin-Resistant A549 Cells to Cisplatin by Inhibition of Nrf2 Pathway

  • Hou, Xiangyu;Bai, Xupeng;Gou, Xiaoli;Zeng, Hang;Xia, Chen;Zhuang, Wei;Chen, Xinmeng;Zhao, Zhongxiang;Huang, Min;Jin, Jing
    • Molecules and Cells
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    • v.38 no.5
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    • pp.396-401
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    • 2015
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA. 3,4,5,5,7-Pentamethoxyflavone (PMF), a natural flavon extracted from Rutaceae plants, sensitized A549/CDDP to CDDP and substantially induced apoptosis compared with that of CDDP alone treated group, and this reversal effect decreased when Nrf2 was downregulated by siRNA. Mechanistically, PMF reduced Nrf2 expression leading to a reduction of Nrf2 downstream genes, and in contrast, this effect was decreased by blocking Nrf2 with siRNA. Taken together, these results demonstrated that PMF could be used as an effective adjuvant sensitizer to increase the efficacy of chemotherapeutic drugs by downregulating Nrf2 signaling pathway.

Progress and Prospect of Rice Biotechnology in Korea

  • Tae Young, Chung
    • Proceedings of the Korean Society of Sericultural Science Conference
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    • 1997.06a
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    • pp.23-49
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    • 1997
  • This is a progress report of rice biotechnology including development of gene transformation system, gene cloning and molecular mapping in rice. The scope of the research was focused on the connection between conventional breeding and biotech-researches. Plant transformation via Agrobacterium or particle bombardment was developed to introduce one or several genes to recommended rice cultivars. Two chimeric genes containing a maize ribosome inactivating protein gene (RIP) and a gerbicide resistant gene (bar) were introduced to Nipponbare, a Japonica cultivar, and transmitted to Korean cultivars. The homozygous progenies of herbicide resistant transgenic plant showed good fertility and agronomic characters. To explore the genetic resourses in rice, over 8,000 cDNA clones from immature rice seed have been isolated and sequenced. About 13% of clones were identified as enzymes related to metabolic pathway. Among them, twenty clones have high homology with genes encoding enzymes in the photorespiratory carbon cycle reaction. Up to now about 100 clones were fully sequenced and registered at EMBL and GenBank. For the mapping of quantitative tarits loci (QTL) and eternal recombinant inbred population with 164 F13 lines (MGRI) was developed from a cross between Milyang 23 and Gihobyeo, Korean rice cultivars. After construction of fully saturated RFLP and AFLP map, quantitative traits using MGRI population were analyzed and integrated into the molecular map. Eighty seven loci were determined with 27 QTL characters including yield and yield components on rice chromosomes. Map based cloning was also tried to isolate semi-dwarf (sd-1) gene in rice. A DNA probe, RG 109, the most tightly linked to sd-1 gene was used to screen from bacterial artifical chromosome (BAC) libraries and five over lapping clones presumably containing sd-1 gene were isolated. Rice genetic database including results of biotech reasearch and classical genetics is provided at Korea Rice Genome Server which is accessible with world wide web (www) browser. The server provides rice cDNA sequences and map informations linked with phenotypic images.

The genomic landscape associated with resistance to aromatase inhibitors in breast cancer

  • Kirithika Sadasivam;Jeevitha Priya Manoharan;Hema Palanisamy;Subramanian Vidyalakshmi
    • Genomics & Informatics
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    • v.21 no.2
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    • pp.20.1-20.10
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    • 2023
  • Aromatase inhibitors (AI) are drugs that are widely used in treating estrogen receptor (ER)-positive breast cancer patients. Drug resistance is a major obstacle to aromatase inhibition therapy. There are diverse reasons behind acquired AI resistance. This study aims at identifying the plausible cause of acquired AI resistance in patients administered with non-steroidal AIs (anastrozole and letrozole). We used genomic, transcriptomic, epigenetic, and mutation data of breast invasive carcinoma from The Cancer Genomic Atlas database. The data was then separated into sensitive and resistant sets based on patients' responsiveness to the non-steroidal AIs. A sensitive set of 150 patients and a resistant set of 172 patients were included for the study. These data were collectively analyzed to probe into the factors that might be responsible for AI resistance. We identified 17 differentially regulated genes (DEGs) among the two groups. Then, methylation, mutation, miRNA, copy number variation, and pathway analyses were performed for these DEGs. The top mutated genes (FGFR3, CDKN2A, RNF208, MAPK4, MAPK15, HSD3B1, CRYBB2, CDC20B, TP53TG5, and MAPK8IP3) were predicted. We also identified a key miRNA - hsa-mir-1264 regulating the expression of CDC20B. Pathway analysis revealed HSD3B1 to be involved in estrogen biosynthesis. This study reveals the involvement of key genes that might be associated with the development of AI resistance in ER-positive breast cancers and hence may act as a potential prognostic and diagnostic biomarker for these patients.

MicroRNA expression profiling in the lungs of genetically different Ri chicken lines against the highly pathogenic avian influenza H5N1 virus

  • Sooyeon Lee;Suyeon Kang;Jubi Heo;Yeojin Hong;Thi Hao Vu;Anh Duc Truong;Hyun S Lillehoj;Yeong Ho Hong
    • Journal of Animal Science and Technology
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    • v.65 no.4
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    • pp.838-855
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    • 2023
  • The highly pathogenic avian influenza (HPAI) virus triggers infectious diseases, resulting in pulmonary damage and high mortality in domestic poultry worldwide. This study aimed to analyze miRNA expression profiles after infection with the HPAI H5N1 virus in resistant and susceptible lines of Ri chickens.For this purpose, resistant and susceptible lines of Vietnamese Ri chicken were used based on the A/G allele of Mx and BF2 genes. These genes are responsible for innate antiviral activity and were selected to determine differentially expressed (DE) miRNAs in HPAI-infected chicken lines using small RNA sequencing. A total of 44 miRNAs were DE after 3 days of infection with the H5N1 virus. Computational program analysis indicated the candidate target genes for DE miRNAs to possess significant functions related to cytokines, chemokines, MAPK signaling pathway, ErBb signaling pathway, and Wnt signaling pathway. Several DE miRNA-mRNA matches were suggested to play crucial roles in mediating immune functions against viral evasion. These results revealed the potential regulatory roles of miRNAs in the immune response of the two Ri chicken lines against HPAI H5N1 virus infection in the lungs.

Characterization of a Chromosomal Nickel Resistance Determinant from Klebsiella oxytoca CCUG 15788

  • Park, Jae-Sun;Lee, Sung-Jae;Rhie, Ho-Gun;Lee, Ho-Sa
    • Journal of Microbiology and Biotechnology
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    • v.18 no.6
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    • pp.1040-1043
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    • 2008
  • Klebsiella oxytoca CCUG 15788 is resistant to $Ni^{2+}$ at a concentration of 10 mM and grows in an inducible manner when exposed to lower concentrations of $Ni^{2+}$. The complete genomic sequence of a 4.2-kb HindIII-digested fragment of this strain was determined from genomic DNA. It was shown to contain four nickel resistance genes (nirA, nirB, nirC, and nirD) encoding transporter and transmembrane proteins for nickel resistance. When the plasmid pKOHI4, encoding nirABCD, was transformed into Escherichia coli JM109, the cells were able to grow in Tris-buffered mineral medium containing 3 mM nickel. TnphoA'-1 insertion mutants in the four nickel genes nirA, nirB, nirC, and nirD showed nickel sensitivity. The nir genes were heterogeneously expressed in E. coli, suggesting functional roles of these genes in nickel resistance.

Expressional Subpopulation of Cancers Determined by G64, a Co-regulated Module

  • Min, Jae-Woong;Choi, Sun Shim
    • Genomics & Informatics
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    • v.13 no.4
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    • pp.132-136
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    • 2015
  • Studies of cancer heterogeneity have received considerable attention recently, because the presence or absence of resistant sub-clones may determine whether or not certain therapeutic treatments are effective. Previously, we have reported G64, a co-regulated gene module composed of 64 different genes, can differentiate tumor intra- or inter-subpopulations in lung adenocarcinomas (LADCs). Here, we investigated whether the G64 module genes were also expressed distinctively in different subpopulations of other cancers. RNA sequencing-based transcriptome data derived from 22 cancers, except LADC, were downloaded from The Cancer Genome Atlas (TCGA). Interestingly, the 22 cancers also expressed the G64 genes in a correlated manner, as observed previously in an LADC study. Considering that gene expression levels were continuous among different tumor samples, tumor subpopulations were investigated using extreme expressional ranges of G64-i.e., tumor subpopulation with the lowest 15% of G64 expression, tumor subpopulation with the highest 15% of G64 expression, and tumor subpopulation with intermediate expression. In each of the 22 cancers, we examined whether patient survival was different among the three different subgroups and found that G64 could differentiate tumor subpopulations in six other cancers, including sarcoma, kidney, brain, liver, and esophageal cancers.

Cre-Lox: A Tool for Removal of Marker Genes to Make GM Foods Safe

  • Zargar, Sajad M.;Mushtaq, Roohi;Joshi, Manisha;Prasad, D. Theertha;Bhat, Nazir Ahmad;Agrawal, Ganesh Kumar;Rakwal, Randeep
    • Journal of Crop Science and Biotechnology
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    • v.10 no.2
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    • pp.73-78
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    • 2007
  • The green revolution has significantly helped in increasing the food production. So far, various breeding methods have been exploited, besides them recombination DNA technology provides another approach for increasing the food production. By means of this technology the losses in food production incurred by various biotic and abiotic stresses can be effectively controlled. In most of the transgenic studies scientists have used antibiotic resistant genes as markers for easy selection of transformants but there are risks involved in use of GM foods. To make such foods safer and environment friendly we have discussed a novel strategy i.e. Cre-lox which involves site specific recombination. By means of Cre-lox the marker genes can be specifically removed once the selection of transformants is over. In addition, this strategy can be used to module the hybrid chromosomes, avoid gene silencing and incorporate single copy of a transgene for its higher expression.

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Resistance to Turnip Mosaic Virus in the Family Brassicaceae

  • Palukaitis, Peter;Kim, Su
    • The Plant Pathology Journal
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    • v.37 no.1
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    • pp.1-23
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    • 2021
  • Resistance to diseases caused by turnip mosaic virus (TuMV) in crop species of the family Brassicaceae has been studied extensively, especially in members of the genus Brassica. The variation in response observed on resistant and susceptible plants inoculated with different isolates of TuMV is due to a combination of the variation in the plant resistome and the variation in the virus genome. Here, we review the breadth of this variation, both at the level of variation in TuMV sequences, with one eye towards the phylogeny and evolution of the virus, and another eye towards the nature of the various responses observed in susceptible vs. different types of resistance responses. The analyses of the viral genomes allowed comparisons of pathotyped viruses on particular indicator hosts to produce clusters of host types, while the inclusion of phylogeny data and geographic location allowed the formation of the host/geographic cluster groups, the derivation of both of which are presented here. Various studies on resistance determination in particular brassica crops sometimes led to further genetic studies, in many cases to include the mapping of genes, and in some cases to the actual identification of the genes. In addition to summarizing the results from such studies done in brassica crops, as well as in radish and Arabidopsis (the latter as a potential source of candidate genes for brassica and radish), we also summarize work done using nonconventional approaches to obtaining resistance to TuMV.

Functional analysis of genes involved in rice disease resistance

  • S.H. Shin;S. R. Yun;Kim, Y C.;B. H. Cho
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.80.1-80
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    • 2003
  • Several plant and microbial genes that could confer disease resistance in transgenic rice plants are being cloned and characterized. We are currently constructing transgenic rice lines that overexpress the gene products, such as a galactinol synthase, a defensin, and a bacterial ACC deaminase. Subtractive hybridization of a rice cDNA library constructed from the Xanthomonas oryzae-infected ice leaves resulted in isolation of many inducible cDNA clones including a elongation factor EF2, a oryzain alpha, a catalase, a aldehyde dehydrogenase, a S-adenosylmethionine synthetase, a caffeic acid O-methyltransferase, a glyceraldehyde-3-phosphate dehydrogenase, a light-regulated protein, nKY transcription factors, and a nucleotide diphosphate kinase. Some genes among those may be useful genetic sources for construction of disease resistant transgenic rice. Full lengths of the rice OsFIERG and a rice oryzain genomic clones were cloned, and serial deletion fragments of the promoter regions of these genes were fused with GUS reporter gene in pCAMBIA1201, respectively. Promoter activities of these constructs will be examined upon various stresses and Pathogen infections to obtain the pathogen specific inducible-promoter. This work was supported by a grant from BioGreen 21 Program, Rural Development Administration, Republic of Korea.

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Screening and Histopathological Characterization of Korean Carrot Lines for Resistance to the Root-Knot Nematode Meloidogyne incognita

  • Seo, Yunhee;Park, Jiyeong;Kim, Yong Su;Park, Yong;Kim, Young Ho
    • The Plant Pathology Journal
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    • v.30 no.1
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    • pp.75-81
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    • 2014
  • In total, 170 carrot lines developed in Korea were screened for resistance to Meloidogyne incognita race 1 to select parental genetic resources useful for the development of nematode-resistant carrot cultivars. Using the gall index (GI), gall formation was examined on carrot roots inoculated with approximately 1,000 second-stage juveniles of the nematode 7 weeks after inoculation. Sixty-one carrot lines were resistant (GI ${\leq}1.0$), while the other 109 were susceptible (GI > 1.0) with coefficient of variance (CV) of GI for total carrot lines 0.68, indicating low-variation of GI within the lines examined. The histopathological responses of two carrot plants from resistant and susceptible lines were examined after nematode infection. In susceptible carrots, giant cells formed with no discernible necrosis around the infecting nematodes. In the resistant carrot line, however, no giant cells formed, although modified cells were observed with extensive formation of necrotic layers through their middle lamella and around the infecting nematodes. This suggested that these structural modifications were related to hypersensitive responses governed by the expression of true resistance genes. Therefore, the Korean carrot lines resistant to the nematode infection are potential genetic resources for the development of quality carrot cultivars resistant to M. incognita race 1.