Alternative Splicing: A Potential Therapeutic Target in Hematological Malignancies.

Leukemia represents the most prevalent malignancy in children, constituting 30% of childhood cancer cases, with acute lymphoblastic leukemia (ALL) being particularly heterogeneous. This paper explores the role of alternative splicing in leukemia, highlighting its significance in cancer development and progression. Aberrant splicing is often driven by mutations in splicing-factor genes, which can lead to the production of variant proteins that contribute to oncogenesis.

Investigation of endoplasmic reticulum stress-regulated chaperones as biomarkers in idiopathic nonobstructive azoospermia.

Azoospermia is a condition in which sperm cells are completely absent in a male's ejaculate. Typically, sperm production occurs in the testes and is regulated by a complex series of cellular and molecular interactions. Endoplasmic reticulum (ER) stress arises when there is a deviation from or damage to the normal functions of the ER within cells.

P53: A key player in diverse cellular processes including nuclear stress and ribosome biogenesis, highlighting potential therapeutic compounds.

The tumor suppressor proteins are key transcription factors involved in the regulation of various cellular processes, such as apoptosis, DNA repair, cell cycle, senescence, and metabolism. The tumor suppressor protein p53 responds to different type of stress signaling, such as hypoxia, DNA damage, nutrient deprivation, oncogene activation, by activating or repressing the expression of different genes that target processes mentioned earlier. p53 has the ability to modulate the activity of many other proteins and signaling pathway through protein-protein interaction, post-translational modifications, or non-coding RNAs.

Advances in molecular function of UPF1 in Cancer.

It is known that more than 10 % of genetic diseases are caused by a mutation in protein-coding mRNA (premature termination codon; PTC). mRNAs with an early stop codon are degraded by the cellular surveillance process known as nonsense-mediated mRNA decay (NMD), which prevents the synthesis of C-terminally truncated proteins. Up-frameshift-1 (UPF1) has been reported to be involved in the downregulation of various cancers, and low expression of UPF1 was shown to correlate with poor prognosis.

Redox Homeostasis and Nrf2-Regulated Mechanisms Are Relevant to Male Infertility.

Infertility represents a significant global health challenge, affecting more than 12% of couples worldwide, and most cases of infertility are caused by male factors. Several pathological pathways are implicated in male infertility. The main mechanisms involved are driven by the loss of reduction-oxidation (redox) homeostasis and the resulting oxidative damage as well as the chronic inflammatory process.

Proteomics analysis identifies the ribosome associated coiled-coil domain-containing protein-124 as a novel interaction partner of nucleophosmin-1.

Background Information: Coiled-coil domain-containing protein-124 (Ccdc124) is a conserved eukaryotic ribosome-associated RNA-binding protein which is involved in resuming ribosome activity after stress-related translational shutdown. Ccdc124 protein is also detected at cellular localizations devoid of ribosomes, such as the centrosome, or the cytokinetic midbody, but its translation-independent cellular function is currently unknown.

Results: By using an unbiased LC-MS/MS-based proteomics approach in human embryonic kidney (HEK293) cells, we identified novel Ccdc124 partners and mapped the cellular organization of interacting proteins, a subset of which are known to be involved in nucleoli biogenesis and function.

Identification of differentially expressed miRNAs and mRNAs associated with the regulation of breast cancer via in silico and in vitro methods.

miRNA expressions are altered during development of breast cancer (BC). The aim of this study is to identify novel cancer-related miRNAs and pathways to understand the mechanisms of BC subtypes. GSE59247 dataset was downloaded from gene expression omnibus (GEO) database and analyzed with GEO2R software.

Recoding of Nonsense Mutation as a Pharmacological Strategy.

Approximately 11% of genetic human diseases are caused by nonsense mutations that introduce a premature termination codon (PTC) into the coding sequence. The PTC results in the production of a potentially harmful shortened polypeptide and activation of a nonsense-mediated decay (NMD) pathway. The NMD pathway reduces the burden of unproductive protein synthesis by lowering the level of PTC mRNA.

extract and 5‑fluorouracil synergistically inhibit the growth of HT-29 colorectal cancer cells by inducing the S phase arrest.

Although 5-fluorouracil (5-FU) is an important anticancer agent for the treatment of colorectal cancer, drug resistance, and dose-related side effects limit the effectiveness of the treatment. Therefore, developing new pharmaceuticals with effective and low toxicity is critically necessary for cancer therapy. This study aimed to investigate the cytotoxic activity of the mushroom extract (CN) on HT-29 human colon cancer cells.

NRF2, a crucial modulator of skin cells protection against vitiligo, psoriasis, and cancer.

The skin represents a physical barrier between the organism and the environment that has evolved to confer protection against biological, chemical, and physical insults. The inner layer, known as dermis, is constituted by connective tissue and different types of immune cells whereas the outer layer, the epidermis, is composed by different layers of keratinocytes and an abundant number of melanocytes, localized in the stratum basale of the epidermis. Oxidative stress is a common alteration of inflammatory skin disorders such as vitiligo, dermatitis, or psoriasis but can also play a causal role in skin carcinogenesis and tumor progression.

An Overview of NRF2-Activating Compounds Bearing α,β-Unsaturated Moiety and Their Antioxidant Effects.

The surge of scientific interest in the discovery of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (NRF2)-activating molecules underscores the importance of NRF2 as a therapeutic target especially for oxidative stress. The chemical reactivity and biological activities of several bioactive compounds have been linked to the presence of α,β-unsaturated structural systems. The α,β-unsaturated carbonyl, sulfonyl and sulfinyl functional groups are reportedly the major α,β-unsaturated moieties involved in the activation of the NRF2 signaling pathway.

Interplay between Non-Coding RNAs and NRF2 in Different Cancers: Spotlight on MicroRNAs and Long Non-Coding RNAs.

Cancer is a multifactorial disease, and a wealth of information has enabled basic and clinical researchers to develop a better conceptual knowledge of the highly heterogeneous nature of cancer. Deregulations of spatio-temporally controlled transduction pathways play a central role in cancer progression. NRF2-driven signaling has engrossed significant attention because of its fundamentally unique features to dualistically regulate cancer progression.

Expression patterns of miR-34a, miR-125b, miR-221 and antioxidant gene NRF2 in plasma samples of patients with atherosclerosis.

Atherosclerosis is one of the main reasons of cardiovascular diseases, the most common cause of death in the world. NRF2 is a critical transcriptional factor that regulates oxidative stress response and contributes to the pathogenesis of atherosclerosis. This study aims to compare the expression levels of miR-34a, miR-125b, miR- 221 and NRF2 in blood samples of patients with atherosclerosis and of controls to find a novel link between microRNAs, oxidative stress and atherosclerosis.

cAMP/PKA-CREB-BDNF signaling pathway in hippocampus of rats subjected to chemically-induced phenylketonuria.

Phenylketonuria (PKU) is an inborn error disease in phenylalanine metabolism resulting from defects in the stages of converting phenylalanine to tyrosine. Although the pathophysiology of PKU is not elucidated yet, the toxic effect of phenylalanine on the brain causes severe mental retardation. In relation to learning and memory, the hippocampal PKA / CREB / BDNF pathway may play a role in learning deficits in PKU patients.

Coiled-coil domain-containing protein-124 (Ccdc124) is a novel RNA binding factor up-regulated in endometrial, ovarian, and urinary bladder cancers.

Background: Coiled-coil domain containing protein-124 (Ccdc124) is a putative mRNA-binding factor associated with cell division, and ribosome biology. Previous reports mentioned an up-regulation of CCDC124 gene in cancer, and listed its mRNA in a molecular prognostic signature in breast cancer.

Objectives: Establishing RNA-binding characteristics of Ccdc124 for a better molecular functional characterization, and carrying-out retrospective studies in order to evaluate its aberrant expression in human cancer samples from various tissue origins.

Identification of miR-17, miR-21, miR-27a, miR-106b and miR-222 as endoplasmic reticulum stress-related potential biomarkers in circulation of patients with atherosclerosis.

Atherosclerosis and related cardiovascular diseases are among the most common causes of death worldwide. Unfolded protein response, also known as Endoplasmic reticulum stress, has a critical role in many diseases including atherosclerosis. Small non-coding microRNAs (miRNA), which generally suppress gene expression, regulate UPR signalling and they may also be involved in the progression of atherosclerosis.

Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer.

Cancer is one of the most fatal diseases with an increasing incidence and mortality all over the world. Thus, there is an urgent need for novel therapies targeting major cancer-related pathways. Nuclear factor-erythroid 2-related factor 2 (NRF2) and its major negative modulator Kelch-like ECH-associated protein 1 (KEAP1) are main players of the cellular defense mechanisms against internal and external cell stressors.

The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives.

The NRF2/KEAP1 pathway is a fundamental signaling cascade that controls multiple cytoprotective responses through the induction of a complex transcriptional program that ultimately renders cancer cells resistant to oxidative, metabolic and therapeutic stress. Interestingly, accumulating evidence in recent years has indicated that metabolic reprogramming is closely interrelated with the regulation of redox homeostasis, suggesting that the disruption of NRF2 signaling might represent a valid therapeutic strategy against a variety of solid and hematologic cancers. These aspects will be the focus of the present review.

Potential Applications of NRF2 Modulators in Cancer Therapy.

The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) regulatory pathway plays an essential role in protecting cells and tissues from oxidative, electrophilic, and xenobiotic stress. By controlling the transactivation of over 500 cytoprotective genes, the NRF2 transcription factor has been implicated in the physiopathology of several human diseases, including cancer. In this respect, accumulating evidence indicates that NRF2 can act as a double-edged sword, being able to mediate tumor suppressive or pro-oncogenic functions, depending on the specific biological context of its activation.

Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs.

Oxidative stress (OS) is associated with many diseases ranging from cancer to neurodegenerative disorders. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is one of the most effective cytoprotective controller against OS. Modulation of Nrf2 pathway constitutes a remarkable strategy in the antineoplastic treatments.

Targeting IRE1 with small molecules counteracts progression of atherosclerosis.

Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation.