Displaying publications 1 - 20 of 34 in total

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  1. Wong KK, Gascoyne DM, Soilleux EJ, Lyne L, Spearman H, Roncador G, et al.
    Oncotarget, 2016 Aug 16;7(33):52940-52956.
    PMID: 27224915 DOI: 10.18632/oncotarget.9507
    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
    Matched MeSH terms: Transcriptome/genetics
  2. Hasunuma T, Ismail KSK, Nambu Y, Kondo A
    J Biosci Bioeng, 2014 Feb;117(2):165-169.
    PMID: 23916856 DOI: 10.1016/j.jbiosc.2013.07.007
    Lignocellulosic biomass dedicated to bioethanol production usually contains pentoses and inhibitory compounds such as furfural that are not well tolerated by Saccharomyces cerevisiae. Thus, S. cerevisiae strains with the capability of utilizing both glucose and xylose in the presence of inhibitors such as furfural are very important in industrial ethanol production. Under the synergistic conditions of transaldolase (TAL) and alcohol dehydrogenase (ADH) overexpression, S. cerevisiae MT8-1X/TAL-ADH was able to produce 1.3-fold and 2.3-fold more ethanol in the presence of 70 mM furfural than a TAL-expressing strain and a control strain, respectively. We also tested the strains' ability by mimicking industrial ethanol production from hemicellulosic hydrolysate containing fermentation inhibitors, and ethanol production was further improved by 16% when using MT8-1X/TAL-ADH compared to the control strain. Transcript analysis further revealed that besides the pentose phosphate pathway genes TKL1 and TAL1, ADH7 was also upregulated in response to furfural stress, which resulted in higher ethanol production compared to the TAL-expressing strain. The improved capability of our modified strain was based on its capacity to more quickly reduce furfural in situ resulting in higher ethanol production. The co-expression of TAL/ADH genes is one crucial strategy to fully utilize undetoxified lignocellulosic hydrolysate, leading to cost-competitive ethanol production.
    Matched MeSH terms: Transcriptome/genetics
  3. Wen WX, Leong CO
    PLoS One, 2019;14(4):e0215381.
    PMID: 31022191 DOI: 10.1371/journal.pone.0215381
    Immune checkpoint inhibitors have demonstrated effective anti-tumour response in cancer types with high mutation burden (e.g. melanoma) and in subset of cancers with features of genomic instability (e.g. mismatch-repair deficiency). One possible explanation for this effect is the increased expression of immune checkpoint molecules and pre-existing adaptive immune response in these cancers. Given that BRCA1 and BRCA2 are integral in maintaining genomic integrity, we hypothesise that the inactivation of these genes may give rise to breast cancers with such immunogenic phenotype. Therefore, using two large series of publicly available breast cancer datasets, namely that from The Cancer Genome Atlas and Wellcome Trust Institute, we sought to investigate the association between BRCA1- and BRCA2-deficiency with features of genomic instability, expression of PD-L1 and PD-1, landscape of inferred tumour-infiltrating immune cells, and T-cell inflamed signature in breast cancers. Here, we report that BRCA1 and BRCA2-deficient breast cancers were associated with features of genomic instability including increased mutation burden. Interestingly, BRCA1-, but not BRCA2-, deficient breast cancers were associated with increased expression of PD-L1 and PD-1, higher abundance of tumour-infiltrating immune cells, and enrichment of T cell-inflamed signature. The differences in immunophenotype between BRCA1- and BRCA2-deficient breast cancers can be attributed, in part, to PTEN gene mutation. Therefore, features of genomic instability such as that mediated by BRCA1- and BRCA2- deficiency in breast cancer were necessary, but not always sufficient, for yielding T cell-inflamed tumour microenvironment, and by extension, predicting clinical benefit from immunotherapy.
    Matched MeSH terms: Transcriptome/genetics
  4. Wong MM, Cannon CH, Wickneswari R
    BMC Genomics, 2011;12:342.
    PMID: 21729267 DOI: 10.1186/1471-2164-12-342
    Acacia auriculiformis × Acacia mangium hybrids are commercially important trees for the timber and pulp industry in Southeast Asia. Increasing pulp yield while reducing pulping costs are major objectives of tree breeding programs. The general monolignol biosynthesis and secondary cell wall formation pathways are well-characterized but genes in these pathways are poorly characterized in Acacia hybrids. RNA-seq on short-read platforms is a rapid approach for obtaining comprehensive transcriptomic data and to discover informative sequence variants.
    Matched MeSH terms: Transcriptome/genetics*
  5. Lee WS, Gudimella R, Wong GR, Tammi MT, Khalid N, Harikrishna JA
    PLoS One, 2015;10(5):e0127526.
    PMID: 25993649 DOI: 10.1371/journal.pone.0127526
    Physiological responses to stress are controlled by expression of a large number of genes, many of which are regulated by microRNAs. Since most banana cultivars are salt-sensitive, improved understanding of genetic regulation of salt induced stress responses in banana can support future crop management and improvement in the face of increasing soil salinity related to irrigation and climate change. In this study we focused on determining miRNA and their targets that respond to NaCl exposure and used transcriptome sequencing of RNA and small RNA from control and NaCl-treated banana roots to assemble a cultivar-specific reference transcriptome and identify orthologous and Musa-specific miRNA responding to salinity. We observed that, banana roots responded to salinity stress with changes in expression for a large number of genes (9.5% of 31,390 expressed unigenes) and reduction in levels of many miRNA, including several novel miRNA and banana-specific miRNA-target pairs. Banana roots expressed a unique set of orthologous and Musa-specific miRNAs of which 59 respond to salt stress in a dose-dependent manner. Gene expression patterns of miRNA compared with those of their predicted mRNA targets indicated that a majority of the differentially expressed miRNAs were down-regulated in response to increased salinity, allowing increased expression of targets involved in diverse biological processes including stress signaling, stress defence, transport, cellular homeostasis, metabolism and other stress-related functions. This study may contribute to the understanding of gene regulation and abiotic stress response of roots and the high-throughput sequencing data sets generated may serve as important resources related to salt tolerance traits for functional genomic studies and genetic improvement in banana.
    Matched MeSH terms: Transcriptome/genetics
  6. Thayale Purayil F, Rajashekar B, S Kurup S, Cheruth AJ, Subramaniam S, Hassan Tawfik N, et al.
    Genes (Basel), 2020 06 10;11(6).
    PMID: 32531994 DOI: 10.3390/genes11060640
    Haloxylon persicum is an endangered western Asiatic desert plant species, which survives under extreme environmental conditions. In this study, we focused on transcriptome analysis of H. persicum to understand the molecular mechanisms associated with drought tolerance. Two different periods of polyethylene glycol (PEG)-induced drought stress (48 h and 72 h) were imposed on H. persicum under in vitro conditions, which resulted in 18 million reads, subsequently assembled by de novo method with more than 8000 transcripts in each treatment. The N50 values were 1437, 1467, and 1524 for the control sample, 48 h samples, and 72 h samples, respectively. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis resulted in enrichment of mitogen-activated protein kinase (MAPK) and plant hormone signal transduction pathways under PEG-induced drought conditions. The differential gene expression analysis (DGEs) revealed significant changes in the expression pattern between the control and the treated samples. The KEGG analysis resulted in mapping transcripts with 138 different pathways reported in plants. The differential expression of drought-responsive transcription factors depicts the possible signaling cascades involved in drought tolerance. The present study provides greater insight into the fundamental transcriptome reprogramming of desert plants under drought.
    Matched MeSH terms: Transcriptome/genetics*
  7. Ng CK, How KY, Tee KK, Chan KG
    Genes (Basel), 2019 04 08;10(4).
    PMID: 30965610 DOI: 10.3390/genes10040282
    Quorum sensing (QS) is a cell-to-cell communication system that uses autoinducers as signaling molecules to enable inter-species and intra-species interactions in response to external stimuli according to the population density. QS allows bacteria such as Acinetobacter baumannii to react rapidly in response to environmental changes and hence, increase the chances of survival. A. baumannii is one of the causative agents in hospital-acquired infections and the number of cases has increased remarkably in the past decade. In this study, A. baumannii strain 863, a multidrug-resistant pathogen, was found to exhibit QS activity by producing N-acyl homoserine lactone. We identified the autoinducer synthase gene, which we named abaI, by performing whole genome sequencing analysis of A. baumannii strain 863. Using high resolution tandem triple quadrupole mass spectrometry, we reported that abaI of A. baumannii strain 863 produced 3-hydroxy-dodecanoyl-homoserine lactone. A gene deletion mutant was constructed, which confirmed the functionality of abaI. A growth defect was observed in the QS-deficient mutant strain. Transcriptome profiling was performed to determine the possible genes regulated by QS. Four groups of genes that showed differential expression were discovered, namely those involved in carbon source metabolism, energy production, stress response and the translation process.
    Matched MeSH terms: Transcriptome/genetics*
  8. Lawson T, Lycett GW, Mayes S, Ho WK, Chin CF
    Mol Biol Rep, 2020 Jun;47(6):4183-4197.
    PMID: 32444976 DOI: 10.1007/s11033-020-05519-y
    The Rab GTPase family plays a vital role in several plant physiological processes including fruit ripening. Fruit softening during ripening involves trafficking of cell wall polymers and enzymes between cellular compartments. Mango, an economically important fruit crop, is known for its delicious taste, exotic flavour and nutritional value. So far, there is a paucity of information on the mango Rab GTPase family. In this study, 23 genes encoding Rab proteins were identified in mango by a comprehensive in silico approach. Sequence alignment and similarity tree analysis with the model plant Arabidopsis as a reference enabled the bona fide assignment of the deduced mango proteins to classify into eight subfamilies. Expression analysis by RNA-Sequencing (RNA-Seq) showed that the Rab genes were differentially expressed in ripe and unripe mangoes suggesting the involvement of vesicle trafficking during ripening. Interaction analysis showed that the proteins involved in vesicle trafficking and cell wall softening were interconnected providing further evidence of the involvement of the Rab GTPases in fruit softening. Correlation analyses showed a significant relationship between the expression level of the RabA3 and RabA4 genes and fruit firmness at the unripe stage of the mango varieties suggesting that the differences in gene expression level might be associated with the contrasting firmness of these varieties. This study will not only provide new insights into the complexity of the ripening-regulated molecular mechanism but also facilitate the identification of potential Rab GTPases to address excessive fruit softening.
    Matched MeSH terms: Transcriptome/genetics
  9. Greenwood MP, Greenwood M, Romanova EV, Mecawi AS, Paterson A, Sarenac O, et al.
    Neurobiol Aging, 2018 05;65:178-191.
    PMID: 29494864 DOI: 10.1016/j.neurobiolaging.2018.01.008
    Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased Avp gene transcription, coincided with reduced Avp promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels. These alterations however did not affect circulating levels of AVP in basal or dehydrated states.
    Matched MeSH terms: Transcriptome/genetics
  10. Abubakar SA, Isa MM, Omar N, Tan SW
    Mol Med Rep, 2020 Dec;22(6):4931-4937.
    PMID: 33174018 DOI: 10.3892/mmr.2020.11560
    The human ocular surface produces highly conserved cationic peptides. Human β‑defensins (HBDs) serve an important role in innate and adaptive immunity. They are primarily expressed in epithelial cells in response to infection and provide the first line of defence against invading microbes. Defensin β1 (DEFB1) is constitutively expressed and regulated by inflammatory mediators including interferon‑γ, lipopolysaccharide and peptidoglycans. DEFB4A is locally induced in response to microbial infection while DEFB109 is induced via Toll‑like receptor 2. The present study examined the expression of the HBD DEFB1, DEFB4A and DEFB109 genes in pterygium. The pterygium tissues and normal conjunctiva samples were obtained from 18 patients undergoing pterygium surgery. The reverse transcription‑quantitative polymerase chain reaction method was employed to determine the expression of DEFB1, DEFB4A and DEFB109 genes. The results revealed that the expression of DEFB1 and DEFB4A was significantly higher and upregulated in pterygium samples when compared with normal conjunctiva samples from each patient (P<0.05), while the expression of DEFB109 was observed to be lower in pterygium samples when compared with normal samples from the same patient. Previous studies have revealed that DEFB1 and DEFB4A genes are present in low concentrations inside the human eye, and they are upregulated during the maturation of keratinocytes, suggesting a possible role in cell differentiation. The DEFB109 gene is present in higher concentrations inside the human eye, though it is newly discovered. It has also been reported that DEFB1 may be involved in carcinogenesis epithelial tumours. Collectively, the current data suggests that HBDs may serve a crucial role in the pathogenesis and development of pterygia, and thus may be considered as novel molecular targets in understanding pterygia development.
    Matched MeSH terms: Transcriptome/genetics
  11. Waiho K, Fazhan H, Shahreza MS, Moh JH, Noorbaiduri S, Wong LL, et al.
    PLoS One, 2017;12(1):e0171095.
    PMID: 28135340 DOI: 10.1371/journal.pone.0171095
    Adequate genetic information is essential for sustainable crustacean fisheries and aquaculture management. The commercially important orange mud crab, Scylla olivacea, is prevalent in Southeast Asia region and is highly sought after. Although it is a suitable aquaculture candidate, full domestication of this species is hampered by the lack of knowledge about the sexual maturation process and the molecular mechanisms behind it, especially in males. To date, data on its whole genome is yet to be reported for S. olivacea. The available transcriptome data published previously on this species focus primarily on females and the role of central nervous system in reproductive development. De novo transcriptome sequencing for the testes of S. olivacea from immature, maturing and mature stages were performed. A total of approximately 144 million high-quality reads were generated and de novo assembled into 160,569 transcripts with a total length of 142.2 Mb. Approximately 15-23% of the total assembled transcripts were annotated when compared to public protein sequence databases (i.e. UniProt database, Interpro database, Pfam database and Drosophila melanogaster protein database), and GO-categorised with GO Ontology terms. A total of 156,181 high-quality Single-Nucleotide Polymorphisms (SNPs) were mined from the transcriptome data of present study. Transcriptome comparison among the testes of different maturation stages revealed one gene (beta crystallin like gene) with the most significant differential expression-up-regulated in immature stage and down-regulated in maturing and mature stages. This was further validated by qRT-PCR. In conclusion, a comprehensive transcriptome of the testis of orange mud crabs from different maturation stages were obtained. This report provides an invaluable resource for enhancing our understanding of this species' genome structure and biology, as expressed and controlled by their gonads.
    Matched MeSH terms: Transcriptome/genetics
  12. Qian M, Zhang H, Kham SK, Liu S, Jiang C, Zhao X, et al.
    Genome Res, 2017 02;27(2):185-195.
    PMID: 27903646 DOI: 10.1101/gr.209163.116
    Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54.1% of patients (n = 125), 31 of which have not been reported previously. In particular, we described a distinct ALL subtype with a characteristic gene expression signature predominantly driven by chromosomal rearrangements of the ZNF384 gene with histone acetyltransferases EP300 and CREBBP ZNF384-rearranged ALL showed significant up-regulation of CLCF1 and BTLA expression, and ZNF384 fusion proteins consistently showed higher activity to promote transcription of these target genes relative to wild-type ZNF384 in vitro. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro. EP300- and CREBBP-ZNF384 fusions resulted in loss of histone lysine acetyltransferase activity in a dominant-negative fashion, with concomitant global reduction of histone acetylation and increased sensitivity of leukemia cells to histone deacetylase inhibitors. In conclusion, our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting.
    Matched MeSH terms: Transcriptome/genetics
  13. Md-Mustafa ND, Khalid N, Gao H, Peng Z, Alimin MF, Bujang N, et al.
    BMC Genomics, 2014;15:984.
    PMID: 25407215 DOI: 10.1186/1471-2164-15-984
    Panduratin A extracted from Boesenbergia rotunda is a flavonoid reported to possess a range of medicinal indications which include anti-dengue, anti-HIV, anti-cancer, antioxidant and anti-inflammatory properties. Boesenbergia rotunda is a plant from the Zingiberaceae family commonly used as a food ingredient and traditional medicine in Southeast Asia and China. Reports on the health benefits of secondary metabolites extracted from Boesenbergia rotunda over the last few years has resulted in rising demands for panduratin A. However large scale extraction has been hindered by the naturally low abundance of the compound and limited knowledge of its biosynthetic pathway.
    Matched MeSH terms: Transcriptome/genetics*
  14. Haris K, Ismail S, Idris Z, Abdullah JM, Yusoff AA
    Asian Pac J Cancer Prev, 2014;15(11):4499-505.
    PMID: 24969876
    Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with 58.6 μg/ml for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.
    Matched MeSH terms: Transcriptome/genetics*
  15. Arloth J, Bogdan R, Weber P, Frishman G, Menke A, Wagner KV, et al.
    Neuron, 2015 Jun 03;86(5):1189-202.
    PMID: 26050039 DOI: 10.1016/j.neuron.2015.05.034
    Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain.
    Matched MeSH terms: Transcriptome/genetics*
  16. Yusuf NH, Ong WD, Redwan RM, Latip MA, Kumar SV
    Gene, 2015 Oct 15;571(1):71-80.
    PMID: 26115767 DOI: 10.1016/j.gene.2015.06.050
    MicroRNAs (miRNAs) are a class of small, endogenous non-coding RNAs that negatively regulate gene expression, resulting in the silencing of target mRNA transcripts through mRNA cleavage or translational inhibition. MiRNAs play significant roles in various biological and physiological processes in plants. However, the miRNA-mediated gene regulatory network in pineapple, the model tropical non-climacteric fruit, remains largely unexplored. Here, we report a complete list of pineapple mature miRNAs obtained from high-throughput small RNA sequencing and precursor miRNAs (pre-miRNAs) obtained from ESTs. Two small RNA libraries were constructed from pineapple fruits and leaves, respectively, using Illumina's Solexa technology. Sequence similarity analysis using miRBase revealed 579,179 reads homologous to 153 miRNAs from 41 miRNA families. In addition, a pineapple fruit transcriptome library consisting of approximately 30,000 EST contigs constructed using Solexa sequencing was used for the discovery of pre-miRNAs. In all, four pre-miRNAs were identified (MIR156, MIR399, MIR444 and MIR2673). Furthermore, the same pineapple transcriptome was used to dissect the function of the miRNAs in pineapple by predicting their putative targets in conjunction with their regulatory networks. In total, 23 metabolic pathways were found to be regulated by miRNAs in pineapple. The use of high-throughput sequencing in pineapples to unveil the presence of miRNAs and their regulatory pathways provides insight into the repertoire of miRNA regulation used exclusively in this non-climacteric model plant.
    Matched MeSH terms: Transcriptome/genetics
  17. Kaur G, Balasubramaniam SD, Lee YJ
    Exp Mol Pathol, 2020 04;113:104362.
    PMID: 31870856 DOI: 10.1016/j.yexmp.2019.104362
    OBJECTIVE: Increased expression of insulin-like growth factor binding protein 2, IGFBP-2, is associated with many cancers, though its role in cervical cancer is unclear. The aim of this study was to investigate the expression of IGFBP-2 protein and the transcriptomics profile of genes involved in the IGF signaling pathway during cervical cancer development.

    DESIGN: Immunohistochemical expression of IGFBP-2 protein was semi-quantitatively assessed in tissue microarrays containing 9 normal cervix, 10 low grade cervical intraepithelial neoplasia (LGCIN), 10 high grade cervical intraepithelial neoplasia (HGCIN) and 42 squamous cell carcinoma (SCC) cases. The gene expression profiles of IGFBP-2, IGF-1, IGF-1R, PTEN, MDM2, AKT1 and TP53 were determined in three cervical tissue samples each from normal cervix, human papillomavirus (HPV)-infected LGCIN, HGCIN and SCC, using Human Transcriptome Array 2.0.

    RESULTS: IGFBP-2 protein was highly expressed in the cytoplasm of SCC cells compared to normal cervix (p = .013). The expression was not significantly associated with CIN grade or SCC stage. Transcriptomics profiling demonstrated upregulation of IGFBP-2 and TP53 in HGCIN and SCC compared to normal cervix. IGF-1, IGF-1R and PTEN genes were downregulated in all histological groups. IGF-1 gene was significantly downregulated in SCC (p = .031), while PTEN gene was significantly downregulated in HGCIN (p = .012), compared to normal cervix. MDM2 and AKT1 genes were downregulated in LGCIN and HGCIN, while upregulated in SCC.

    CONCLUSION: In cervical carcinogenesis, IGFBP-2 appears to play an oncogenic role, probably through an IGF-independent mechanism.

    Matched MeSH terms: Transcriptome/genetics
  18. Foong LC, Chai JY, Ho ASH, Yeo BPH, Lim YM, Tam SM
    Sci Rep, 2020 09 30;10(1):16123.
    PMID: 32999341 DOI: 10.1038/s41598-020-72997-2
    Impatiens balsamina L. is a tropical ornamental and traditional medicinal herb rich in natural compounds, especially 2-methoxy-1,4-naphthoquinone (MNQ) which is a bioactive compound with tested anticancer activities. Characterization of key genes involved in the shikimate and 1,4-dihydroxy-2-naphthoate (DHNA) pathways responsible for MNQ biosynthesis and their expression profiles in I. balsamina will facilitate adoption of genetic/metabolic engineering or synthetic biology approaches to further increase production for pre-commercialization. In this study, HPLC analysis showed that MNQ was present in significantly higher quantities in the capsule pericarps throughout three developmental stages (early-, mature- and postbreaker stages) whilst its immediate precursor, 2-hydroxy-1,4-naphthoquinone (lawsone) was mainly detected in mature leaves. Transcriptomes of I. balsamina derived from leaf, flower, and three capsule developmental stages were generated, totalling 59.643 Gb of raw reads that were assembled into 94,659 unigenes (595,828 transcripts). A total of 73.96% of unigenes were functionally annotated against seven public databases and 50,786 differentially expressed genes (DEGs) were identified. Expression profiles of 20 selected genes from four major secondary metabolism pathways were studied and validated using qRT-PCR method. Majority of the DHNA pathway genes were found to be significantly upregulated in early stage capsule compared to flower and leaf, suggesting tissue-specific synthesis of MNQ. Correlation analysis identified 11 candidate unigenes related to three enzymes (NADH-quinone oxidoreductase, UDP-glycosyltransferases and S-adenosylmethionine-dependent O-methyltransferase) important in the final steps of MNQ biosynthesis based on genes expression profiles consistent with MNQ content. This study provides the first molecular insight into the dynamics of MNQ biosynthesis and accumulation across different tissues of I. balsamina and serves as a valuable resource to facilitate further manipulation to increase production of MNQ.
    Matched MeSH terms: Transcriptome/genetics*
  19. Moradipoor S, Ismail P, Etemad A, Wan Sulaiman WA, Ahmadloo S
    Biomed Res Int, 2016;2016:1845638.
    PMID: 27781209 DOI: 10.1155/2016/1845638
    Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM) and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT(2) Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.
    Matched MeSH terms: Transcriptome/genetics*
  20. Rahman F, Hassan M, Rosli R, Almousally I, Hanano A, Murphy DJ
    PLoS One, 2018;13(5):e0196669.
    PMID: 29771926 DOI: 10.1371/journal.pone.0196669
    Bioinformatics analyses of caleosin/peroxygenases (CLO/PXG) demonstrated that these genes are present in the vast majority of Viridiplantae taxa for which sequence data are available. Functionally active CLO/PXG proteins with roles in abiotic stress tolerance and lipid droplet storage are present in some Trebouxiophycean and Chlorophycean green algae but are absent from the small number of sequenced Prasinophyceaen genomes. CLO/PXG-like genes are expressed during dehydration stress in Charophyte algae, a sister clade of the land plants (Embryophyta). CLO/PXG-like sequences are also present in all of the >300 sequenced Embryophyte genomes, where some species contain as many as 10-12 genes that have arisen via selective gene duplication. Angiosperm genomes harbour at least one copy each of two distinct CLO/PX isoforms, termed H (high) and L (low), where H-forms contain an additional C-terminal motif of about 30-50 residues that is absent from L-forms. In contrast, species in other Viridiplantae taxa, including green algae, non-vascular plants, ferns and gymnosperms, contain only one (or occasionally both) of these isoforms per genome. Transcriptome and biochemical data show that CLO/PXG-like genes have complex patterns of developmental and tissue-specific expression. CLO/PXG proteins can associate with cytosolic lipid droplets and/or bilayer membranes. Many of the analysed isoforms also have peroxygenase activity and are involved in oxylipin metabolism. The distribution of CLO/PXG-like genes is consistent with an origin >1 billion years ago in at least two of the earliest diverging groups of the Viridiplantae, namely the Chlorophyta and the Streptophyta, after the Viridiplantae had already diverged from other Archaeplastidal groups such as the Rhodophyta and Glaucophyta. While algal CLO/PXGs have roles in lipid packaging and stress responses, the Embryophyte proteins have a much wider spectrum of roles and may have been instrumental in the colonisation of terrestrial habitats and the subsequent diversification as the major land flora.
    Matched MeSH terms: Transcriptome/genetics
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