scholarly journals Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2462 ◽  
Author(s):  
Kha Wai Hon ◽  
Syafiq Asnawi Zainal Abidin ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Regulation Of Gene Expression ◽  
High Energy ◽  
Metabolic Reprogramming ◽  
Cancer Hallmarks ◽  
Fatty Acids Metabolism

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with a high mortality rate globally. The pathophysiology of CRC is mainly initiated by alteration in gene expression, leading to dysregulation in multiple signalling pathways and cellular processes. Metabolic reprogramming is one of the important cancer hallmarks in CRC, which involves the adaptive changes in tumour cell metabolism to sustain the high energy requirements for rapid cell proliferation. There are several mechanisms in the metabolic reprogramming of cancer cells, such as aerobic glycolysis, oxidative phosphorylation, lactate and fatty acids metabolism. MicroRNAs (miRNAs) are a class of non-coding RNAs that are responsible for post-transcriptional regulation of gene expression. Differential expression of miRNAs has been shown to play an important role in different aspects of tumorigenesis, such as proliferation, apoptosis, and drug resistance, as well as metabolic reprogramming. Increasing evidence also reports that miRNAs could function as potential regulators of metabolic reprogramming in CRC cells. This review provides an insight into the role of different miRNAs in regulating the metabolism of CRC cells as well as to discuss the potential role of miRNAs as biomarkers or therapeutic targets in CRC tumour metabolism.

The F1Fo-ATPase inhibitor, IF1, is a critical regulator of energy metabolism in cancer cells

2021 ◽  
Vol 49 (2) ◽  
pp. 815-827
Author(s):  
Giancarlo Solaini ◽  
Gianluca Sgarbi ◽  
Alessandra Baracca
Keyword(s):  
Cancer Cells ◽  
Atp Synthase ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Endogenous Inhibitor ◽  
Atpase Inhibitor ◽  
Molecular Action ◽  
F1fo Atpase

In the last two decades, IF1, the endogenous inhibitor of the mitochondrial F1Fo-ATPase (ATP synthase) has assumed greater and ever greater interest since it has been found to be overexpressed in many cancers. At present, several findings indicate that IF1 is capable of playing a central role in cancer cells by promoting metabolic reprogramming, proliferation and resistance to cell death. However, the mechanism(s) at the basis of this pro-oncogenic action of IF1 remains elusive. Here, we recall the main features of the mechanism of the action of IF1 when the ATP synthase works in reverse, and discuss the experimental evidence that support its relevance in cancer cells. In particular, a clear pro-oncogenic action of IF1 is to avoid wasting of ATP when cancer cells are exposed to anoxia or near anoxia conditions, therefore favoring cell survival and tumor growth. However, more recently, various papers have described IF1 as an inhibitor of the ATP synthase when it is working physiologically (i.e. synthethizing ATP), and therefore reprogramming cell metabolism to aerobic glycolysis. In contrast, other studies excluded IF1 as an inhibitor of ATP synthase under normoxia, providing the basis for a hot debate. This review focuses on the role of IF1 as a modulator of the ATP synthase in normoxic cancer cells with the awareness that the knowledge of the molecular action of IF1 on the ATP synthase is crucial in unravelling the molecular mechanism(s) responsible for the pro-oncogenic role of IF1 in cancer and in developing related anticancer strategies.

scholarly journals Interleukin-33 regulates metabolic reprogramming of the retinal pigment epithelium in response to immune stressors

2021 ◽  
Author(s):  
Louis M Scott ◽  
Emma E Vincent ◽  
Natalie Hudson ◽  
Chris Neal ◽  
Nicholas Jones ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Metabolic Reprogramming ◽  
Mitochondrial Morphology ◽  
Interleukin 33 ◽  
Stress Signals

SummaryIt remains unresolved how retinal pigment epithelial (RPE) cell metabolism is regulated following immune activation to maintain retinal homeostasis and retinal function. We exposed RPE to several stress signals, particularly toll-like receptor stimulation, and uncovered an ability of RPE to adapt their metabolic preference on aerobic glycolysis or oxidative glucose metabolism in response to different immune stimuli. We have identified interleukin-33 (IL-33) as a key metabolic checkpoint that antagonises the Warburg effect to ensure the functional stability of the RPE. The identification of IL-33 as a key regulator of mitochondrial metabolism suggests roles for the cytokine that go beyond its extracellular “alarmin” activities. IL-33 exerts control over mitochondrial respiration in RPE by facilitating oxidative pyruvate catabolism. We have also revealed that in the absence of IL-33, mitochondrial function declines and resultant bioenergetic switching is aligned with altered mitochondrial morphology. Our data not only sheds new light in the molecular pathway of activation of mitochondrial respiration in RPE in response to immune stressors, but also uncovers a novel role of nuclear intrinsic IL-33 as a metabolic checkpoint regulator.

scholarly journals Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD

2021 ◽  
Vol 8 ◽  
Author(s):  
Roberto Pagliarini ◽  
Christine Podrini
Keyword(s):  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Metabolic Reprogramming ◽  
Comprehensive Overview ◽  
Computational Data ◽  
Cellular Pathways ◽  
Autosomal Dominant Polycystic Kidney ◽  
Experimental Findings ◽  
Glutamine Uptake

Metabolic reprogramming is a key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD) characterized by changes in cellular pathways occurring in response to the pathological cell conditions. In ADPKD, a broad range of dysregulated pathways have been found. The studies supporting alterations in cell metabolism have shown that the metabolic preference for abnormal cystic growth is to utilize aerobic glycolysis, increasing glutamine uptake and reducing oxidative phosphorylation, consequently resulting in ADPKD cells shifting their energy to alternative energetic pathways. The mechanism behind the role of the polycystin proteins and how it leads to disease remains unclear, despite the identification of numerous signaling pathways. The integration of computational data analysis that accompanies experimental findings was pivotal in the identification of metabolic reprogramming in ADPKD. Here, we summarize the important results and argue that their exploitation may give further insights into the regulative mechanisms driving metabolic reprogramming in ADPKD. The aim of this review is to provide a comprehensive overview on metabolic focused studies and potential targets for treatment, and to propose that computational approaches could be instrumental in advancing this field of research.

scholarly journals Regulation of Gene Expression Associated With the N6-Methyladenosine (m6A) Enzyme System and Its Significance in Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Shuoran Tian ◽  
Junzhong Lai ◽  
Tingting Yu ◽  
Qiumei Li ◽  
Qi Chen
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor Genes ◽  
Enzyme System ◽  
Cell Metabolism ◽  
Regulation Of Gene Expression ◽  
Rna Modification ◽  
Special Role ◽  
Biological Functions ◽  
Altered Expression

N6-methyladenosine (m6A), an important RNA modification, is a reversible behavior catalyzed by methyltransferase complexes (m6A “writers”), demethylated transferases (m6A “erasers”), and binding proteins (m6A “readers”). It plays a vital regulatory role in biological functions, involving in a variety of physiological and pathological processes. The level of m6A will affect the RNA metabolism including the degradation of mRNA, and processing or translation of the modified RNA. Its abnormal changes will lead to disrupting the regulation of gene expression and promoting the occurrence of aberrant cell behavior. The abnormal expression of m6A enzyme system can be a crucial impact disturbing the abundance of m6A, thus affecting the expression of oncogenes or tumor suppressor genes in various types of cancer. In this review, we elucidate the special role of m6A “writers”, “erasers”, and “readers” in normal physiology, and how their altered expression affects the cell metabolism and promotes the occurrence of tumors. We also discuss the potential to target these enzymes for cancer diagnosis, prognosis, and the development of new therapies.

scholarly journals Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3018
Author(s):  
Marek Samec ◽  
Alena Liskova ◽  
Lenka Koklesova ◽  
Kevin Zhai ◽  
Elizabeth Varghese ◽  
...  
Keyword(s):  
Cancer Metabolism ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Effective Prevention ◽  
Anti Cancer ◽  
Glucose 6 Phosphate Dehydrogenase

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

Speciation and changes in male gene expression in Drosophila

Genome ◽  
2020 ◽  
pp. 1-11
Author(s):  
Bahar Patlar ◽  
Alberto Civetta
Keyword(s):  
Gene Expression ◽  
Reproductive Isolation ◽  
Potential Role ◽  
Regulation Of Gene Expression ◽  
Drosophila Model ◽  
Depth Analysis ◽  
The Impact ◽  
Plastic Responses ◽  
Male Gene

It has long been acknowledged that changes in the regulation of gene expression may account for major organismal differences. However, we still do not fully understand how changes in gene expression evolve and how do such changes influence organisms’ differences. We are even less aware of the impact such changes might have in restricting gene flow between species. Here, we focus on studies of gene expression and speciation in the Drosophila model. We review studies that have identified gene interactions in post-mating reproductive isolation and speciation, particularly those that modulate male gene expression. We also address studies that have experimentally manipulated changes in gene expression to test their effect in post-mating reproductive isolation. We highlight the need for a more in-depth analysis of the role of selection causing disrupted gene expression of such candidate genes in sterile/inviable hybrids. Moreover, we discuss the relevance to incorporate more routinely assays that simultaneously evaluate the potential effects of environmental factors and genetic background in modulating plastic responses in male genes and their potential role in speciation.

scholarly journals The nucleoplasmic interactions among Lamin A/C-pRB-LAP2α-E2F1 are modulated by dexamethasone

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anastasia Ricci ◽  
Sara Orazi ◽  
Federica Biancucci ◽  
Mauro Magnani ◽  
Michele Menotta
Keyword(s):  
Gene Expression ◽  
Cell Cycle Progression ◽  
Regulation Of Gene Expression ◽  
Lamin A ◽  
Wild Type ◽  
Cycle Progression ◽  
C Dynamics ◽  
E2f Transcription Factor ◽  
Transcription Factor 1

AbstractAtaxia telangiectasia (AT) is a rare genetic neurodegenerative disease. To date, there is no available cure for the illness, but the use of glucocorticoids has been shown to alleviate the neurological symptoms associated with AT. While studying the effects of dexamethasone (dex) in AT fibroblasts, by chance we observed that the nucleoplasmic Lamin A/C was affected by the drug. In addition to the structural roles of A-type lamins, Lamin A/C has been shown to play a role in the regulation of gene expression and cell cycle progression, and alterations in the LMNA gene is cause of human diseases called laminopathies. Dex was found to improve the nucleoplasmic accumulation of soluble Lamin A/C and was capable of managing the large chromatin Lamin A/C scaffolds contained complex, thus regulating epigenetics in treated cells. In addition, dex modified the interactions of Lamin A/C with its direct partners lamin associated polypeptide (LAP) 2a, Retinoblastoma 1 (pRB) and E2F Transcription Factor 1 (E2F1), regulating local gene expression dependent on E2F1. These effects were differentially observed in both AT and wild type (WT) cells. To our knowledge, this is the first reported evidence of the role of dex in Lamin A/C dynamics in AT cells, and may represent a new area of research regarding the effects of glucocorticoids on AT. Moreover, future investigations could also be extended to healthy subjects or to other pathologies such as laminopathies since glucocorticoids may have other important effects in these contexts as well.

scholarly journals The Role of Translation Initiation Regulation in Haematopoiesis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Control ◽  
Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

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