Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer.

Background: Breast cancer manifests as a heterogeneous pathology marked by complex metabolic reprogramming essential to satisfy its energy demands. Oncogenic signals boost the metabolism, modifying fatty acid synthesis and glucose use from the onset to progression and therapy resistant-forms. However, the exact contribution of metabolic dependencies during tumor evolution remains unclear.

The mA-independent role of epitranscriptomic factors in cancer.

Protein function alteration and protein mislocalization are cancer hallmarks that drive oncogenesis. N-methyladenosine (mA) deposition mediated by METTL3, METTL16, and METTL5 together with the contribution of additional subunits of the mA system, has shown a dramatic impact on cancer development. However, the cellular localization of mA proteins inside tumor cells has been little studied so far.

Deregulation of New Cell Death Mechanisms in Leukemia.

Hematological malignancies are among the top five most frequent forms of cancer in developed countries worldwide. Although the new therapeutic approaches have improved the quality and the life expectancy of patients, the high rate of recurrence and drug resistance are the main issues for counteracting blood disorders. Chemotherapy-resistant leukemic clones activate molecular processes for biological survival, preventing the activation of regulated cell death pathways, leading to cancer progression.

3D-printed biosensors in biomedical applications exploiting plasmonic phenomena and antibody self-assembled monolayers.

In this work, a 3D-printed plasmonic chip based on a silver-gold bilayer was developed in order to enhance the optical response of the surface plasmon resonance (SPR) probe. More specifically, numerical and experimental results were obtained on the 3D-printed SPR platform based on a silver-gold bilayer. Then, the optimized probe's gold plasmonic interface was functionalized with a specific antibody directed against the p27 protein (p27), an important cell cycle regulator.

Involvement of regulated cell deaths in aging and age-related pathologies.

Aging is a pathophysiological process that causes a gradual and permanent reduction in all biological system functions. The phenomenon is caused by the accumulation of endogenous and exogenous damage as a result of several stressors, resulting in significantly increased risks of various age-related diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. In addition, aging appears to be connected with mis-regulation of programmed cell death (PCD), which is required for regular cell turnover in many tissues sustained by cell division.

SIRT1 activation promotes energy homeostasis and reprograms liver cancer metabolism.

Background: Cancer cells are characterized by uncontrolled cell proliferation and impaired bioenergetics. Sirtuins are a family of highly conserved enzymes that play a fundamental role in energy metabolism regulation. SIRT1, in particular, drives many physiological stress responses and metabolic pathways following nutrient deprivation.

HAT1: Landscape of Biological Function and Role in Cancer.

Histone modifications, as key chromatin regulators, play a pivotal role in the pathogenesis of several diseases, such as cancer. Acetylation, and more specifically lysine acetylation, is a reversible epigenetic process with a fundamental role in cell life, able to target histone and non-histone proteins. This epigenetic modification regulates transcriptional processes and protein activity, stability, and localization.

Emerging Roles of SIRT5 in Metabolism, Cancer, and SARS-CoV-2 Infection.

Sirtuin 5 (SIRT5) is a predominantly mitochondrial enzyme catalyzing the removal of glutaryl, succinyl, malonyl, and acetyl groups from lysine residues through a NAD-dependent deacylase mechanism. SIRT5 is an important regulator of cellular homeostasis and modulates the activity of proteins involved in different metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, fatty acid oxidation, electron transport chain, generation of ketone bodies, nitrogenous waste management, and reactive oxygen species (ROS) detoxification. SIRT5 controls a wide range of aspects of myocardial energy metabolism and plays critical roles in heart physiology and stress responses.

FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) and prostate cancer (PCa) are among the most prevalent malignant tumors worldwide. There is now a comprehensive understanding of metabolic reprogramming as a hallmark of cancer. Fatty acid synthase (FASN) is a key regulator of the lipid metabolic network, providing energy to favor tumor proliferation and development.

NAA60 (HAT4): the newly discovered bi-functional Golgi member of the acetyltransferase family.

Chromatin structural organization, gene expression and proteostasis are intricately regulated in a wide range of biological processes, both physiological and pathological. Protein acetylation, a major post-translational modification, is tightly involved in interconnected biological networks, modulating the activation of gene transcription and protein action in cells. A very large number of studies describe the pivotal role of the so-called acetylome (accounting for more than 80% of the human proteome) in orchestrating different pathways in response to stimuli and triggering severe diseases, including cancer.

Histone lysine demethylase inhibition reprograms prostate cancer metabolism and mechanics.

Objective: Aberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced PCa. Although direct AR signaling inhibitors exist, AR expression and function can also be epigenetically regulated.

SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers.

SARS-CoV-2 spike protein detection through a plasmonic D-shaped plastic optical fiber aptasensor.

A specific aptameric sequence has been immobilized on short polyethyleneglycol (PEG) interface on gold nano-film deposited on a D-shaped plastic optical fiber (POFs) probe, and the protein binding has been monitored exploiting the very sensitive surface plasmon resonance (SPR) phenomenon. The receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein has been specifically used to develop an aptasensor. Surface analysis techniques coupled to fluorescence microscopy and plasmonic analysis have been utilized to characterize the biointerface.

Gene Transactivation and Transrepression in MYC-Driven Cancers.

is a proto-oncogene regulating a large number of genes involved in a plethora of cellular functions. Its deregulation results in activation of gene expression and/or an increase in MYC protein stability. overexpression is a hallmark of malignant growth, inducing self-renewal of stem cells and blocking senescence and cell differentiation.

The Two-Faced Role of SIRT6 in Cancer.

Sirtuin 6 (SIRT6) is a NAD-dependent nuclear deacylase and mono-ADP-ribosylase with a wide spectrum of substrates. Through its pleiotropic activities, SIRT6 modulates either directly or indirectly key processes linked to cell fate determination and oncogenesis such as DNA damage repair, metabolic homeostasis, and apoptosis. SIRT6 regulates the expression and activity of both pro-apoptotic (e.

Discovery of novel tetrahydrobenzo[b]thiophene-3-carbonitriles as histone deacetylase inhibitors.

The discovery and development of isoform-selective histone deacetylase (HDAC) inhibitor is a challenging task because of the sequence homology among HDAC enzymes. In the present work, novel tetrahydro benzo[b]thiophene-3-carbonitrile based benzamides were designed, synthesized, and evaluated as HDAC inhibitors. Pharmacophore modeling was our main design strategy, and two novel series of tetrahydro benzo[b]thiophene-3-carbonitrile derivatives with piperidine linker (series 1) and piperazine linker (series 2) were identified as HDAC inhibitors.

Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models.

Positive Regulatory Domain (PRDM) gene family members commonly express two main molecular variants, the PR- isoform usually acting as tumor suppressor and the PR- one functioning as oncogene. Accordingly, PRDM2/RIZ encodes for RIZ1 (PR-) and RIZ2 (PR-). In human cancers, genetic or epigenetic modifications induce RIZ1 silencing with an expression level imbalance in favor of RIZ2 that could be relevant for tumorigenesis.

The Role of Necroptosis: Biological Relevance and Its Involvement in Cancer.

Regulated cell death mechanisms are essential for the maintenance of cellular homeostasis. Evasion of cell death is one of the most important hallmarks of cancer. Necroptosis is a caspase independent form of regulated cell death, investigated as a novel therapeutic strategy to eradicate apoptosis resistant cancer cells.

Deregulation of Cell Death in Cancer: Recent Highlights.

The aim of this Special Issue on the deregulation of cell death in cancer is to bring together recent perspectives on the relationship between tumorigenesis and programmed cell death (PCD) [...

Recent insights into : biological function and involvement in pathogenesis.

Acetylation of histone and non-histone proteins is a post-translational modification mostly associated with activation of gene transcription. The first histone acetyltransferase (HAT) identified as modifying newly synthesized histone H4 in yeast was a type B HAT named . Although it was the first HAT to be discovered, HAT1 remains one of the most poorly studied enzymes in its class.