The role of LSM1 in breast cancer: Shaping metabolism and tumor-associated macrophage infiltration.

LSM1 is part of the cytoplasmic protein complex Lsm1-7-Pat1 and is likely involved in pre-mRNA degradation by aiding U4/U6 snRNP formation. More research is needed to uncover LSM1's potential in breast cancer (BRCA) clinical pathology, the tumor immune microenvironment, and precision oncology. We discovered LSM1 as a diagnostic marker for advanced BRCA with poor survival, using a multi-omics approach. We studied LSM1 expression across BRCA regions and its link to immune cells through various methods, including spatial transcriptomics and single-cell RNA-sequencing. We also examined how silencing LSM1 affects mitochondrial function and energy metabolism in the tumor environment. These findings were confirmed using 54 BRCA patient biopsies and tissue microarrays. Immunofluorescence and bioinformatics assessed LSM1's connection to clinicopathological features and prognosis. This study uncovers gene patterns linked to breast cancer, with LSM1 linked to macrophage energy processes. Silencing LSM1 in breast cancer cells disrupts mitochondria and energy metabolism. Spatial analysis aligns with previous results, showing LSM1's connection to macrophages. Biopsies confirm LSM1 elevation in advanced breast cancer with increased macrophage presence. To summarize, LSM1 changes may drive BRCA progression, making it a potential diagnostic and prognostic marker. It also influences energy metabolism and the tumor's immune environment during metastasis, showing promise for precision medicine and drug screening in BRCA.

The Cross-Communication of Cuproptosis and Regulated Cell Death in Human Pathophysiology.

Copper (Cu) plays a crucial and diverse function in biological systems, acting as a cofactor at numerous sites of enzymatic activity and participating in various physiological processes, including oxidative stress regulation, lipid metabolism, and energy metabolism. Similar to other micronutrients, the body regulates Cu levels to ensure homeostasis; any disruption in Cu homeostasis may result in various illnesses. Cuproptosis causes proteotoxic stress and ultimately results in cell death by the binding of Cu ions to lipid-acylated proteins during the tricarboxylic acid cycle of mitochondrial respiration. Cu is not only involved in regulatory cell death (RCD), but also in exogenous factors that induce cellular responses and toxic outcomes. Cu imbalances also affect the transmission of several RCD messages. Therefore, this article presents a thorough examination of the mechanisms involved in Cu-induced RCD as well as the role of Cu complexes in its pathophysiology.

Single-cell landscape and spatial transcriptomic analysis reveals macrophage infiltration and glycolytic metabolism in kidney renal clear cell carcinoma.

The present study investigates the clinical relevance of glycolytic factors, specifically PGAM1, in the tumor microenvironment of kidney renal clear cell carcinoma (KIRC). Despite the established role of glycolytic metabolism in cancer pathophysiology, the prognostic implications and key targets in KIRC remain elusive. We analyzed GEO and TCGA datasets to identify DEGs in KIRC and studied their relationship with immune gene expression, survival, tumor stage, gene mutations, and infiltrating immune cells. We explored Pgam1 gene expression in different kidney regions using spatial transcriptomics after mouse kidney injury analysis. Single-cell RNA-sequencing was used to assess the association of PGAM1 with immune cells. Findings were validated with tumor specimens from 60 KIRC patients, correlating PGAM1 expression with clinicopathological features and prognosis using bioinformatics and immunohistochemistry. We demonstrated the expression of central gene regulators in renal cancer in relation to genetic variants, deletions, and tumor microenvironment. Mutations in these hub genes were positively associated with distinct immune cells in six different immune datasets and played a crucial role in immune cell infiltration in KIRC. Single-cell RNA-sequencing revealed that elevated PGAM1 was associated with immune cell infiltration, specifically macrophages. Furthermore, pharmacogenomic analysis of renal cancer cell lines indicated that inactivation of PGAM1 was associated with increased sensitivity to specific small-molecule drugs. Altered PGAM1 in KIRC is associated with disease progression and immune microenvironment. It has diagnostic and prognostic implications, indicating its potential in precision medicine and drug screening.

NLRP3 inflammasome activation, metabolic danger signals, and protein binding partners.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an oligomeric complex that assembles in response to exogenous signals of pathogen infection and endogenous danger signals of non-microbial origin. When NLRP3 inflammasome assembly activates caspase-1, it promotes the maturation and release of the inflammatory cytokines interleukin-1B and IL-18. Aberrant activation of the NLRP3 inflammasome has been implicated in various diseases, including chronic inflammatory, metabolic, and cardiovascular diseases. The NLRP3 inflammasome can be activated through several principal mechanisms, including K+ efflux, lysosomal damage, and the production of mitochondrial reactive oxygen species. Interestingly, metabolic danger signals activate the NLRP3 inflammasome to induce metabolic diseases. NLRP3 contains three crucial domains: an N-terminal pyrin domain, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat domain. Protein-protein interactions act as a 'pedal or brake' to control the activation of the NLRP3 inflammasome. In this review, we present the mechanisms underlying NLRP3 inflammasome activation after induction by metabolic danger signals or via protein-protein interactions with NLRP3 that likely occur in metabolic diseases. Understanding these mechanisms will enable the development of specific inhibitors to treat NLRP3-related metabolic diseases.

Mitochondrial Dysfunction and Oxidative Stress in Aging and Disease.

Mitochondria are considered to have a significant influence on aging due to their critical role in the regulation of bioenergetics, oxidative stress, and cell death [...].

Prognostic significance of ferroptosis pathway gene signature and correlation with macrophage infiltration in cervical squamous cell carcinoma.

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NFE2L2) plays a critical role in ferroptosis and biogenesis, however, its role in cervical squamous cell carcinoma (CESC) remains unknown. Therefore, in this study, we aimed to determine the role of NFE2L2 in CESC using multiomic analysis. METHODS: All raw data were downloaded from The Cancer Genome Atlas (TCGA) and further validated in our dataset. NFE2L2 mRNA expression and methylation data on CESC were examined using the Tumor Immune Estimation Resource (TIMER) and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database resources. NFE2L2 expression was examined in paraffin-embedded tissues from our cohort of 240 samples each of cancerous and non-cancerous tissues. Further, cervical cancer biopsies were genetically validated. TIMER and Tumor-Immune System Interactions Database (TISIDB) were used to analyze the correlation between NFE2L2 and cluster of differentiation 163 (CD163) with co-expressed genes in tumor-infiltrating immune cells. RESULTS: The mRNA and protein levels of NFE2L2 were lower in CESC tissues than they were in adjacent tissues. Importantly, a low NFE2L2 level correlated with poor prognosis in CESC patients. NFE2L2 was specifically expressed in tumor macrophages and correlated with the tumor immune landscape and poor prognosis in the cohort data. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis showed that co-expressed genes are mainly associated with multiple immune-related pathways. Furthermore, our data analysis revealed that NFE2L2 and macrophage CD163 expression levels were negatively correlated. Interestingly, we discovered multiple NFE2L2 binding sites in promoters of CD163. CONCLUSION: This study confirmed the novel pyroptosis landscape in CESC, provided a role for NFE2L2 in the tumor microenvironment, and identified prognostic biomarkers for CESC and related immune infiltration.