scholarly journals MicroRNA Regulation of Glycolytic Metabolism in Glioblastoma

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Huda Alfardus ◽  
Alan McIntyre ◽  
Stuart Smith
Keyword(s):  
Aerobic Glycolysis ◽  
Signalling Pathways ◽  
Glycolytic Metabolism ◽  
Malignant Brain Tumour ◽  
Coding Sequences ◽  
Microrna Regulation ◽  
Regulation Of Metabolism ◽  
Cancer Types ◽  
Mirnas Expression ◽  
Oncogenic Signalling

Glioblastoma (GBM) is the most aggressive and common malignant brain tumour in adults. A well-known hallmark of GMB and many other tumours is aerobic glycolysis. MicroRNAs (miRNAs) are a class of short nonprotein coding sequences that exert posttranscriptional controls on gene expression and represent critical regulators of aerobic glycolysis in GBM. In GBM, miRNAs regulate the expression of glycolytic genes directly and via the regulation of metabolism-associated tumour suppressors and oncogenic signalling pathways. This review aims to establish links between miRNAs expression levels, the expression of GBM glycolytic regulatory genes, and the malignant progression and prognosis of GBM. In this review, the involvement of 25 miRNAs in the regulation of glycolytic metabolism of GBM is discussed. Seven of these miRNAs have been shown to regulate glycolytic metabolism in other tumour types. Further eight miRNAs, which are differentially expressed in GBM, have also been reported to regulate glycolytic metabolism in other cancer types. Thus, these miRNAs could serve as potential glycolytic regulators in GBM but will require functional validation. As such, the characterisation of these molecular and metabolic signatures in GBM can facilitate a better understanding of the molecular pathogenesis of this disease.

Signal Transduction of a Novel WBP2 Oncogene

2020 ◽  
Vol 14 (01) ◽  
pp. 3-13
Author(s):  
Tinghine Chu ◽  
Sock Hong Seah ◽  
Yoon Pin Lim
Keyword(s):  
Breast Cancer ◽  
Cancer Development ◽  
Signalling Pathways ◽  
Ww Domain ◽  
Growing Body ◽  
Cancer Types ◽  
Near Future ◽  
Oncogenic Signalling ◽  
Hippo Signalling

WW-domain binding protein 2 (WBP2) was first discovered as a ligand of the WW-domain of Yes-associated Protein (YAP). A decade after its discovery, our laboratory implicated WBP2 in breast cancer development. Since then, WBP2 had also been shown to be involved in other types of cancer, such as glioma, liver and skin cancer. The oncogenic properties of WBP2 are mediated by several oncogenic signalling pathways, including EGFR, PI3K/Akt, ER, Wnt, and Hippo signalling pathways. Recently, WBP2 was demonstrated to play roles in diseases other than cancer, such as infertility and deafness. In the near future, we envisage a growing body of literature surrounding the role of WBP2 in more cancer types and signalling pathways.

scholarly journals Broccoli Consumption Interacts with GSTM1 to Perturb Oncogenic Signalling Pathways in the Prostate

PLoS ONE ◽  
2008 ◽  
Vol 3 (7) ◽  
pp. e2568 ◽  
Author(s):  
Maria Traka ◽  
Amy V. Gasper ◽  
Antonietta Melchini ◽  
James R. Bacon ◽  
Paul W. Needs ◽  
...  
Keyword(s):  
Signalling Pathways ◽  
Oncogenic Signalling

scholarly journals A systems pharmacology approach based on oncogenic signalling pathways to determine the mechanisms of action of natural products in breast cancer from transcriptome data

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Regan Odongo ◽  
Asuman Demiroglu-Zergeroglu ◽  
Tunahan Çakır
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Complex Diseases ◽  
Mechanisms Of Action ◽  
Signalling Pathways ◽  
Breast Cancer Cell Lines ◽  
Transcriptome Data ◽  
Oncogenic Signalling

Abstract Background Narrow spectrum of action through limited molecular targets and unforeseen drug-related toxicities have been the main reasons for drug failures at the phase I clinical trials in complex diseases. Most plant-derived compounds with medicinal values possess poly-pharmacologic properties with overall good tolerability, and, thus, are appropriate in the management of complex diseases, especially cancers. However, methodological limitations impede attempts to catalogue targeted processes and infer systemic mechanisms of action. While most of the current understanding of these compounds is based on reductive methods, it is increasingly becoming clear that holistic techniques, leveraging current improvements in omic data collection and bioinformatics methods, are better suited for elucidating their systemic effects. Thus, we developed and implemented an integrative systems biology pipeline to study these compounds and reveal their mechanism of actions on breast cancer cell lines. Methods Transcriptome data from compound-treated breast cancer cell lines, representing triple negative (TN), luminal A (ER+) and HER2+ tumour types, were mapped on human protein interactome to construct targeted subnetworks. The subnetworks were analysed for enriched oncogenic signalling pathways. Pathway redundancy was reduced by constructing pathway-pathway interaction networks, and the sets of overlapping genes were subsequently used to infer pathway crosstalk. The resulting filtered pathways were mapped on oncogenesis processes to evaluate their anti-carcinogenic effectiveness, and thus putative mechanisms of action. Results The signalling pathways regulated by Actein, Withaferin A, Indole-3-Carbinol and Compound Kushen, which are extensively researched compounds, were shown to be projected on a set of oncogenesis processes at the transcriptomic level in different breast cancer subtypes. The enrichment of well-known tumour driving genes indicate that these compounds indirectly dysregulate cancer driving pathways in the subnetworks. Conclusion The proposed framework infers the mechanisms of action of potential drug candidates from their enriched protein interaction subnetworks and oncogenic signalling pathways. It also provides a systematic approach for evaluating such compounds in polygenic complex diseases. In addition, the plant-based compounds used here show poly-pharmacologic mechanism of action by targeting subnetworks enriched with cancer driving genes. This network perspective supports the need for a systemic drug-target evaluation for lead compounds prior to efficacy experiments.

METABOLISM OF RAM TESTICULAR SPERMATOZOA IN THE PRESENCE OF TESTOSTERONE AND RELATED STEROIDS

1970 ◽  
Vol 65 (3) ◽  
pp. 565-576 ◽  
Author(s):  
J. K. Voglmayr ◽  
R. N. Murdoch ◽  
I. G. White
Keyword(s):  
Aerobic Glycolysis ◽  
Rete Testis ◽  
Glycolytic Metabolism ◽  
Anaerobic Conditions ◽  
Aerobic Conditions ◽  
Testicular Spermatozoa ◽  
Almost All ◽  
Oxidation Of Glucose

ABSTRACT The effects of testosterone* and related steroids on the oxidative and glycolytic metabolism of freshly collected ram testicular spermatozoa and of spermatozoa stored under air in rete testis fluid for 3 days at 3°C have been studied. When freshly collected testicular spermatozoa were incubated with glucose under aerobic conditions only a small proportion of the utilized glucose could be accounted for as lactate. The addition of a number of steroids, including testosterone, androstanedione, 5β-androstanedione, androsterone, epiandrosterone and 5β-androsterone, greatly increased aerobic glycolysis, the oxidation of the substrate and the proportion of the utilized substrate converted to lactic acid. After 3 days storage at 3°C, testicular spermatozoa respired at a greater rate than spermatozoa freshly collected from the testes. Although the stimulating effect of steroids on aerobic glycolysis increased after storage, they depressed rather than stimulated the oxidation of glucose by stored testicular spermatozoa. With the exception of androstanedione, which slightly stimulated glycolysis, storage of testicular spermatozoa for 3 days in the presence of steroids did not significantly influence their subsequent metabolism when washed free of the steroids. Both freshly collected and stored ram testicular spermatozoa displayed a marked Pasteur effect, and utilized more glucose and produced more lactate under anaerobic than under aerobic conditions. In the absence of oxygen the steroids did not stimulate glycolysis to any extent. However, epiandrosterone depressed the glycolysis of freshly collected spermatozoa under anaerobic conditions and after storage, 5β-androsterone had a similar effect. Androstanedione, 5β-androstanedione, epiandrosterone and 5β-androsterone were the most effective steroids in altering the metabolism of testicular spermatozoa and, under almost all conditions of incubation, depressed the synthesis of amino acids from glucose. The results suggest that the effects of testosterone and related steroids in vitro may depend on the age of the spermatozoa after their release from the Sertoli cells; the steroid effects may have important consequences in vivo in relation to sperm maturation.

scholarly journals Obesity-associated cancer: an immunological perspective

2015 ◽  
Vol 75 (2) ◽  
pp. 125-138 ◽  
Author(s):  
Melissa J. Conroy ◽  
Margaret R. Dunne ◽  
Claire L. Donohoe ◽  
John V. Reynolds
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Inflammatory Cells ◽  
Epidemiological Studies ◽  
Signalling Pathways ◽  
Immune Balance ◽  
Immune Cell Subsets ◽  
Cancer Types ◽  
Endocrine Factors

Epidemiological studies have established an association between obesity, insulin resistance, type 2 diabetes and a number of cancer types. Research has focused predominantly on altered endocrine factors, growth factors and signalling pathways, with little known in man about the immune involvement in the relevant pathophysiological processes. Moreover, in an era of exciting new breakthroughs in cancer immunotherapy, there is also a need to study the safety and efficacy of immunotherapeutics in the complex setting of inflammatory-driven obesity-associated cancer. This review addresses key immune cell subsets underpinning obesity-associated inflammation and describes how such immune compartments might be targeted to prevent and treat obesity-associated cancer. We propose that the modulation, metabolism, migration and abundance of pro- and anti-inflammatory cells and tumour-specific T cells might be therapeutically altered to both restore immune balance, alleviating pathological inflammation, and to improve anti-tumour immune responses in obesity-associated cancer.

The roles of miRNAs’ clinical efficiencies in the colorectal cancer pathobiology: A review article

2020 ◽  
Vol 28 (4) ◽  
pp. 273-285
Author(s):  
Nahal Eshghifar ◽  
Elham Badrlou ◽  
Farkhondeh Pouresmaeili
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Meta Analysis ◽  
Review Article ◽  
Expression Data ◽  
Translational Study ◽  
Number Of Genes ◽  
Speed Up ◽  
Cancer Types ◽  
Mirnas Expression

MiRNAs (microRNAs) are defined as micro directors and regulators of gene expression. Since altered miRNA expression is signified in the pathobiology of diverse cancers such as colorectal cancers (CRCs), these molecules are described as therapeutic targets, either. Manipulation of miRNAs could lead to further therapy for chemo and radio-resistant CRCs. The usage of microRNAs has indicated prominent promise in the prognosis and diagnosis of CRC, because of their unique expression pattern associated with cancer types and malignancies. Nowadays, many researchers are analyzing the correlation between miRNA polymorphisms and cancer risk. With continuous incompatibility in colorectal cancer (CRC) miRNAs expression data, it is critical to move toward the content of a “pre-laboratory” analysis to speed up efficient accuracy medicine and translational study. Pathway study for the highest expressed miRNAs- regulated target genes resulted in the identification of a considerable number of genes associated with CRC pathway including PI3K, TGFβ, and APC. In this review, we aimed to collect fruitful information about miRNAs and their potential roles in CRC, and provide a meta-analysis of the most frequently studied miRNAs in association with the disease.

scholarly journals Lowest expressing microRNAs capture indispensable information: identifying cancer types

2016 ◽  
Author(s):  
Roni Rasnic ◽  
Nathan Linial ◽  
Michal Linial
Keyword(s):  
Expression Profiles ◽  
Substantial Improvement ◽  
The Cancer Genome Atlas ◽  
Unknown Primary ◽  
Support Vector ◽  
Cancer Tissue ◽  
Average Recall ◽  
Tissue Identification ◽  
Cancer Types ◽  
Mirnas Expression

ABSTRACTThe primary function of microRNAs (miRNAs) is to maintain cell homeostasis. In cancerous tissues miRNAs’ expression undergo drastic alterations. In this study, we used miRNA expression profiles from The Cancer Genome Atlas (TCGA) of 24 cancer types and 3 healthy tissues, collected from >8500 samples. We seek to classify the cancer’s origin and tissue identification using the expression from 1046 reported miRNAs. Despite an apparent uniform appearance of miRNAs among cancerous samples, we recover indispensable information from lowly expressed miRNAs regarding the cancer/tissue types. Multiclass support vector machine classification yields an average recall of 58% in identifying the correct tissue and tumor types. Data discretization has led to substantial improvement reaching an average recall of 91% (95% median). We propose a straightforward protocol as a crucial step in classifying tumors of unknown primary origin. Our counter-intuitive conclusion is that in almost all cancer types, highly expressing miRNAs mask the significant signal that lower expressed miRNAs provide.

scholarly journals Phenotypic and microRNA transcriptomic profiling of the MDA-MB-231 spheroid-enriched CSCs with comparison of MCF-7 microRNA profiling dataset

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3551 ◽  
Author(s):  
Lily Boo ◽  
Wan Yong Ho ◽  
Norlaily Mohd Ali ◽  
Swee Keong Yeap ◽  
Huynh Ky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Expression Profiles ◽  
Signalling Pathways ◽  
Surface Markers ◽  
Phenotypic Characteristics ◽  
Microrna Profiling ◽  
Mirnas Expression ◽  
Cancer Spheroids ◽  
Mcf 7

Breast cancer spheroids have been widely used as in vitro models of cancer stem cells (CSCs), yet little is known about their phenotypic characteristics and microRNAs (miRNAs) expression profiles. The objectives of this research were to evaluate the phenotypic characteristics of MDA-MB-231 spheroid-enriched cells for their CSCs properties and also to determine their miRNAs expression profile. Similar to our previously published MCF-7 spheroid, MDA-MB-231 spheroid also showed typical CSCs characteristics namely self-renewability, expression of putative CSCs-related surface markers and enhancement of drug resistance. From the miRNA profile, miR-15b, miR-34a, miR-148a, miR-628 and miR-196b were shown to be involved in CSCs-associated signalling pathways in both models of spheroids, which highlights the involvement of these miRNAs in maintaining the CSCs features. In addition, unique clusters of miRNAs namely miR-205, miR-181a and miR-204 were found in basal-like spheroid whereas miR-125, miR-760, miR-30c and miR-136 were identified in luminal-like spheroid. Our results highlight the roles of miRNAs as well as novel perspectives of the relevant pathways underlying spheroid-enriched CSCs in breast cancer.

Immunometabolism regulates TCR recycling and iNKT cell functions

2019 ◽  
Vol 12 (570) ◽  
pp. eaau1788 ◽  
Author(s):  
Sicheng Fu ◽  
Shasha Zhu ◽  
Chenxi Tian ◽  
Shiyu Bai ◽  
Jiqian Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Aerobic Glycolysis ◽  
Mammalian Target Of Rapamycin ◽  
Glycolytic Metabolism ◽  
Hexokinase Ii ◽  
Inkt Cells ◽  
Tcr Signaling ◽  
Immune Synapse ◽  
Cell Functions ◽  
Ifn Γ

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor (TCR), which recognizes glycolipid antigens presented on CD1d molecules. These cells are phenotypically and functionally distinct from conventional T cells. When we characterized the metabolic activity of iNKT cells, consistent with their activated phenotype, we found that they had much less mitochondrial respiratory capacity but increased glycolytic activity in comparison to naïve conventional CD4+ T cells. After TCR engagement, iNKT cells further increased aerobic glycolysis, which was important for the expression of interferon-γ (IFN-γ). Glycolytic metabolism promoted the translocation of hexokinase-II to mitochondria and the activation of mammalian target of rapamycin complex 2 (mTORC2). Inhibiting glycolysis reduced the activity of Akt and PKCθ, which inhibited TCR recycling and accumulation within the immune synapse. Diminished TCR accumulation in the immune synapse reduced the activation of proximal and distal TCR signaling pathways and IFN-γ production in activated iNKT cells. Our studies demonstrate that glycolytic metabolism augments TCR signaling duration and IFN-γ production in iNKT cells by increasing TCR recycling.

scholarly journals Targeting translation: eIF4E as an emerging anticancer drug target

2016 ◽  
Vol 18 ◽  
Author(s):  
Chunwan Lu ◽  
Levi Makala ◽  
Daqing Wu ◽  
Yafei Cai
Keyword(s):  
Drug Target ◽  
Therapy Resistance ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Signalling Pathways ◽  
Signalling Network ◽  
Distinct Level ◽  
Selective Translation ◽  
Rate Limiting ◽  
Oncogenic Signalling

The translation initiation factor eIF4E mediates a rate-limiting process that drives selective translation of many oncongenic proteins such as cyclin D1, survivin and VEGF, thereby contributing to tumour growth, metastasis and therapy resistance. As an essential regulatory hub in cancer signalling network, many oncogenic signalling pathways appear to converge on eIF4E. Therefore, targeting eIF4E-mediated cap-dependent translation is considered a promising anticancer strategy. This paper reviews the strategies that can be used to target eIF4E, highlighting agents that target eIF4E activity at each distinct level.

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