Multiomics-based energy metabolism heterogeneity and its regulation by antiparasite drug ivermectin.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18080-e18080
Author(s):  
Na Li ◽  
Xianquan Zhan
Keyword(s):  
Ovarian Cancer ◽  
Energy Metabolism ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Differentially Expressed ◽  
Molecular Networks ◽  
Differentially Expressed Proteins ◽  
Proteomics Data ◽  
Lactate Shuttle ◽  
Ovarian Cancers

e18080 Background: Energy metabolism heterogeneity is a hallmark in ovarian cancer, namely the Warburg effect and the reverse Warburg effects coexist in ovarian cancer. Exploration of energy metabolism heterogeneity benefits for discovery of the effective biomarkers for ovarian cancers. Methods: Comprehensive analysis of mitochondrial proteomics data (1198 mitochondrial differentially expressed proteins), mitochondrial phosphorpoteomics data (67 mitochondrial phosphorproteins), proteomics data (205 differentially expressed proteins), and transcriptomics data (20115 genes in 419 ovarian cancer samples) was useful. Results: It revealed (i) the upregulations of rate-limiting enzymes PKM2 in glycolysis, IDH2 in Kreb’s cycle, and UQCRH in oxidative phosphorylation (OXPHOS) pathways, (ii) the upregulation of PDHB that converts pyruvate from glycolysis into acetyl-CoA in Kreb’s cycle. Anti-parasite drug ivermectin demonstrated its strong abilities to inhibit proliferation and cell cycle progression and promote apoptosis in EOC cells, through molecular networks to target PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in OXPHOS, and MCT1 and MCT4 in lactate shuttle to inhibit EOC growth. Those results were further confirmed in the ovarian cancer cell models and tissues. Conclusions: It clearly concluded that ivermectin might have new potential for ovarian cancer treatment through regulating energy metabolism pathways. These findings provide more accurate understanding of molecular mechanisms of ovarian cancers and discovery of effective energy-metabolism-heterogeneity-based therapeutic drugs for ovarian cancers.

scholarly journals Identification of Differentially Expressed Proteins in Sugarcane in Response to Infection by Xanthomonas albilineans Using iTRAQ Quantitative Proteomics

2020 ◽  
Vol 8 (1) ◽  
pp. 76
Author(s):  
Jian-Yu Meng ◽  
Mbuya Sylvain Ntambo ◽  
Philippe C. Rott ◽  
Hua-Ying Fu ◽  
Mei-Ting Huang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Vascular System ◽  
Lipid Transfer Protein ◽  
Differentially Expressed ◽  
Post Inoculation ◽  
Differentially Expressed Proteins ◽  
Lipid Transfer ◽  
Leaf Scald ◽  
Improvement Programs ◽  
Xanthomonas Albilineans

Sugarcane can suffer severe yield losses when affected by leaf scald, a disease caused by Xanthomonas albilineans. This bacterial pathogen colonizes the vascular system of sugarcane, which can result in reduced plant growth and plant death. In order to better understand the molecular mechanisms involved in the resistance of sugarcane to leaf scald, a comparative proteomic study was performed with two sugarcane cultivars inoculated with X. albilineans: one resistant (LCP 85-384) and one susceptible (ROC20) to leaf scald. The iTRAQ (isobaric tags for relative and absolute quantification) approach at 0 and 48 h post-inoculation (hpi) was used to identify and annotate differentially expressed proteins (DEPs). A total of 4295 proteins were associated with 1099 gene ontology (GO) terms by GO analysis. Among those, 285 were DEPs during X. albilineans infection in cultivars LCP 85-384 and ROC20. One hundred seventy-two DEPs were identified in resistant cultivar LCP 85-384, and 113 of these proteins were upregulated and 59 were downregulated. One hundred ninety-two DEPs were found in susceptible cultivar ROC20 and half of these (92) were upregulated, whereas the other half corresponded to downregulated proteins. The significantly upregulated DEPs in LCP 85-384 were involved in metabolic pathways, the biosynthesis of secondary metabolites, and the phenylpropanoid biosynthesis pathway. Additionally, the expression of seven candidate genes related to photosynthesis and glycolytic pathways, plant innate immune system, glycosylation process, plant cytochrome P450, and non-specific lipid transfer protein was verified based on transcription levels in sugarcane during infection by X. albilineans. Our findings shed new light on the differential expression of proteins in sugarcane cultivars in response to infection by X. albilineans. The identification of these genes provides important information for sugarcane variety improvement programs using molecular breeding strategies.

scholarly journals PSXIII-30 Analysis of gene expression profiles in liver and muscle tissue of pigs divergent in feed efficiency

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 475-475
Author(s):  
Stafford Vigors ◽  
Torres Sweeney
Keyword(s):  
Energy Metabolism ◽  
Immune Function ◽  
Feed Efficiency ◽  
Molecular Mechanisms ◽  
Protein Targeting ◽  
Expression Profiles ◽  
Cell Signalling ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Joint Analysis

Abstract The improvement of feed efficiency is a key economic goal within the pig production industry. The objective of this study was to examine transcriptomic differences in both the liver and muscle in pigs divergent for feed efficiency, thus improving our understanding of the molecular mechanisms influencing feed efficiency and enabling the identification of candidate biomarkers. Residual feed intake (RFI) was calculated in two populations of pigs from two different farms of origin. The 6 most efficient (LRFI) and 6 least efficient (HRFI) animals in each population were selected for further analysis of Longissimus Dorsi muscle and liver. Three different analysis were performed: 1) Identification of differentially expressed genes (DE) in liver, 2) Identification of DE genes in muscle and 3) Identification of genes commonly DE in both tissues. Hierarchical clustering revealed that transcriptomic data segregated based on the RFI value of the pig rather than farm of origin. A total of 6464 genes were identified as being differentially expressed (DE) in muscle, while 964 genes were identified as being DE in liver. In the muscle-only analysis, genes associated with RNA, protein synthesis and energy metabolism were downregulated in the LRFI animals while in the liver-only analysis, genes associated with cell signalling and lipid homeostasis were upregulated in the LRFI animals. Genes that were commonly DE between muscle and liver (n = 526) were used for the joint analysis. These 526 genes were associated with protein targeting to membrane, extracellular matrix organization and immune function. There are pathways common to both muscle and liver in particular genes associated with immune function. In contrast, tissue-specific pathways contributing to differences in feed efficiency were also identified with genes associated with energy metabolism identified in muscle and lipid metabolism in liver. This study identifies key mechanisms driving changes in feed efficiency in pigs.

scholarly journals Comparative iTRAQ proteomics revealed proteins associated with lobed fin regeneration in Bichirs

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Suxiang Lu ◽  
Qian Xiong ◽  
Kang Du ◽  
Xiaoni Gan ◽  
Xuzhen Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Multiple Reaction Monitoring ◽  
Limb Regeneration ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Differentially Expressed Proteins ◽  
Absolute Quantitation ◽  
Bioinformatics Analyses ◽  
Fin Regeneration ◽  
Early Stages

Abstract Background Polypterus senegalus can fully regenerate its pectoral lobed fins, including a complex endoskeleton, with remarkable precision. However, despite the enormous potential of this species for use in medical research, its regeneration mechanisms remain largely unknown. Methods To identify the differentially expressed proteins (DEPs) during the early stages of lobed fin regeneration in P. senegalus, we performed a differential proteomic analysis using isobaric tag for relative and absolute quantitation (iTRAQ) approach based quantitative proteome from the pectoral lobed fins at 3 time points. Furthermore, we validated the changes in protein expression with multiple-reaction monitoring (MRM) analysis. Results The experiment yielded a total of 3177 proteins and 15,091 unique peptides including 1006 non-redundant (nr) DEPs. Of these, 592 were upregulated while 349 were downregulated after lobed fin amputation when compared to the original tissue. Bioinformatics analyses showed that the DEPs were mainly associated with Ribosome and RNA transport, metabolic, ECM-receptor interaction, Golgi and endoplasmic reticulum, DNA replication, and Regulation of actin cytoskeleton. Conclusions To our knowledge, this is the first proteomic research to investigate alterations in protein levels and affected pathways in bichirs’ lobe-fin/limb regeneration. In addition, our study demonstrated a highly dynamic regulation during lobed fin regeneration in P. senegalus. These results not only provide a comprehensive dataset on differentially expressed proteins during the early stages of lobe-fin/limb regeneration but also advance our understanding of the molecular mechanisms underlying lobe-fin/limb regeneration.

scholarly journals iTRAQ Quantitative Analysis of Multidrug Resistance Mechanisms in Human Gastric Cancer Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Huai-Dong Hu ◽  
Feng Ye ◽  
Da-Zhi Zhang ◽  
Peng Hu ◽  
Hong Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multidrug Resistance ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Absolute Quantification ◽  
Differentially Expressed ◽  
Human Gastric Cancer ◽  
Differentially Expressed Proteins ◽  
Gastric Cancer Cells ◽  
Proteomic Approach

Multidrug resistance (MDR) is a major obstacle towards a successful treatment of gastric cancer. However, the mechanisms of MDR are intricate and have not been fully understood. To elucidate the molecular mechanisms of MDR in gastric cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the vincristine-resistant SGC7901/VCR cell line and its parental SGC7901 cell line as a model. In total, 820 unique proteins were identified and 91 proteins showed to be differentially expressed in SGC7901/VCR compared with SGC7901. Several differentially expressed proteins were further validated by western blot analysis. Furthermore, the association of MVP, one of the highly expressed proteins in SGC7901/VCR, with MDR was verified. Our study is the first application of iTRAQ technology for MDR mechanisms analysis in gastric cancer, and many of the differentially expressed proteins identified have not been linked to MDR in gastric cancer before, which showed the value of this technology in identifying differentially expressed proteins in cancer.

scholarly journals Identification of differentially expressed proteins in fresh and frozen–thawed boar spermatozoa by iTRAQ-coupled 2D LC–MS/MS

Reproduction ◽  
2014 ◽  
Vol 147 (3) ◽  
pp. 321-330 ◽  
Author(s):  
Xiaoli Chen ◽  
Huabin Zhu ◽  
Chuanhuo Hu ◽  
Haisheng Hao ◽  
Junfang Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatic Analysis ◽  
Absolute Quantification ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Protein Levels ◽  
Boar Semen ◽  
Isobaric Tags ◽  
Boar Spermatozoa

Cryodamage is a major problem in semen cryopreservation, causing changes in the levels of proteins that influence the function and motility of spermatozoa. In this study, protein samples prepared from fresh and frozen–thawed boar spermatozoa were compared using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique coupled to 2D LC–MS/MS analysis. A total of 41 differentially expressed proteins were identified and quantified, including 35 proteins that were present at higher levels and six proteins that were present at lower levels in frozen–thawed spermatozoa by at least a mean of 1.79-fold (P<0.05). On classifying into ten distinct categories using bioinformatic analysis, most of the 41 differentially expressed proteins were found to be closely relevant to sperm premature capacitation, adhesions, energy supply, and sperm–oocyte binding and fusion. The expression of four of these proteins, SOD1, TPI1, ODF2, and AKAP3, was verified by western blot analysis. We propose that alterations in these identified proteins affect the quality of cryopreserved semen and ultimately lower its fertilizing capacity. This is the first study to compare protein levels in fresh and frozen–thawed spermatozoa using the iTRAQ technology. Our preliminary results provide an overview of the molecular mechanisms of cryodamage in frozen–thawed spermatozoa and theoretical guidance to improve the cryopreservation of boar semen.

scholarly journals Quantitative Proteomics Analysis to Study the Protective Effects of Nerve Growth Factor on Hippocampal Mitochondria in VD Rats

2021 ◽  
Author(s):  
Yanmei Zhang ◽  
yuan yao ◽  
Runxiu Zhu ◽  
Niyang Aida ◽  
Jun Yuan ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Clinical Syndrome ◽  
Differentially Expressed ◽  
Protective Effects ◽  
Differentially Expressed Proteins ◽  
Sprague Dawley ◽  
Nerve Growth

Abstract Background Vascular dementia (VD) is a kind of clinical syndrome characterized with the impairment cognitive function caused by cerebrovascular disease. Genetics, biochemical, and morphological analyses of cell and animal models, reveal that mitochondria could have roles in this neurodegeneration. Methods We used Sprague-Dawley rats to establish VD model, and used the proteomics method based on relative quantification (iTRAQ) to identify the differentially expressed proteins in hippocampus mitochondria. Results A total of 33 differentially expressed proteins were identified between the VD rats and the VD rats treated with nerve growth factor groups. And five differentially expressed proteins (Rgs14, Slc7a14, Ppm1l, Kcnj10 and Syngr1) were identified after completing the sham-operate control, VD rats and VD rats treated with nerve growth factor groups, then successfully confirmed by western blot. Bioinformatics analysis suggested that the mitochondrial molecular mechanism of VD and the protective effect of nerve growth factor on mitochondrial function of VD rats may be due to different molecular mechanisms. Conclusion We estimated that mitochondrial dysfunction may be the onset of VD and key role in the pathological process of VD. This study not only has a deeper understanding of the mitochondrial molecular mechanism of VD, but also is helpful for the screening of drug targets.

scholarly journals Odd-skipped related 2 (OSR2) is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Cell Fate ◽  
Microarray Data ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Differentially Expressed ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2,3). We previously identified forkhead box L2 (4), (FOXL2) as among the genes whose expression was most different in HGSC ovarian tumors when compared to the ovary. Here, we find that potential FOXL2 transcriptional target (5,6) odd-skipped related gene OSR2 (7) is differentially expressed in high-grade serous ovarian cancer, and could be observed in independent tumor microarray data (2,3). These data reveal perturbed expression of a target gene of a key transcription factor and specifier of ovarian cell fate in high-grade serous ovarian cancers.

scholarly journals PEG3 is differentially expressed in high-grade serous ovarian cancers.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Ovarian Cancer ◽  
Expression Profiles ◽  
Gynecologic Cancer ◽  
Gene Expression Profiles ◽  
Ovarian Tumors ◽  
Differentially Expressed ◽  
High Grade ◽  
Normal Ovary ◽  
Primary Tumors ◽  
Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1-3). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (4, 5). We identified paternally expressed gene 3 (PEG3) (6) as among the genes whose expression was most different in HGSC ovarian tumors. PEG3 expression was significantly lower in ovarian tumors relative to normal ovary. In one dataset, an anti-sense transcript produced at the PEG3 locus was among those most differentially expressed between HGSC tumors and benign ovarial tissue. These data indicate that significant changes in expression at the PEG3 imprinted locus could be a feature of high-grade serous ovarian cancers.

scholarly journals Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4029
Author(s):  
Sandra Muñoz-Galván ◽  
Amancio Carnero
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Therapy Resistance ◽  
Omics Technologies ◽  
Gynecological Malignancy ◽  
Tumor Relapse ◽  
Molecular Features ◽  
Ovarian Cancers ◽  
Late Detection

Ovarian cancer is a major cause of fatality due to a gynecological malignancy. This lethality is largely due to the unspecific clinical manifestations of ovarian cancer, which lead to late detection and to high resistance to conventional therapies based on platinum. In recent years, we have advanced our understanding of the mechanisms provoking tumor relapse, and the advent of so-called omics technologies has provided exceptional tools to evaluate molecular mechanisms leading to therapy resistance in ovarian cancer. Here, we review the contribution of genomics, transcriptomics, and epigenomics techniques to our knowledge about the biology and molecular features of ovarian cancers, with a focus on therapy resistance. The use of these technologies to identify molecular markers and mechanisms leading to chemoresistance in these tumors is discussed, as well as potential further applications.

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