Gene Function Research Articles

Iron Overload, Oxidative Stress, and Somatic Mutations in MDS: What Is the Association?

Iron overload (IOL) accumulates in myelodysplastic syndromes (MDS) from expanded erythropoiesis and transfusions. Somatic mutations (SM) are frequent in MDS and stratify patient risk. MDS treatments reversing or limiting transfusion dependence are limited. The literature was reviewed on how IOL and oxidative stress interact with specific SM in MDS to influence cellular physiology. PubMed searches included keywords of each specific mutation combined with iron, oxidative stress, and reactive oxygens species (ROS). Papers relevant to hematopoietic stem/progenitor cells, the bone marrow microenvironment, MDS, AML or other myeloid disorders were preferred. Included were the most frequent SM in MDS, SM of the International Prognostic Scoring System-Molecular (IPSS-M), of familial predisposing conditions and the CMML PSS-molecular. About 31 SM plus four familial conditions were searched. Discussed are the frequency of each SM, whether function is gained or lost, early or late SM status, a function of the unmutated gene, and function considering iron and oxidative stress. Given limited effective MDS therapies, considering how IOL and ROS interact with SM to influence cellular physiology in the hematopoietic system, increasing bone marrow failure progression or malignant transformation may be of benefit and support optimization of measures to reduce IOL or neutralize ROS.

Epigenetic Mechanisms Driving Human Evolutionary Changes

A crucial aspect of our comprehension of human evolution is epigenetics, the study of heritable modifications in gene function that do not include modifications in the DNA sequence. This intriguing field of study emphasises on how reversible and environmental-sensitive mechanisms, such as histone, DNA methylation, and non-coding RNA activity, control gene expression and support phenotypic variation. These techniques allow animals to adapt to changing environments without experiencing permanent genetic changes, providing a flexible basis for evolutionary processes. Understanding human evolution now heavily relies on epigenetics. Since animals can adapt to changing environments without enduring permanent genetic changes, evolutionary processes have a flexible basis. Epigenetic modifications have closely linked characteristics such as immune system function and brain development throughout human evolution. Epigenetic patterns have been impacted by environmental factors like diet, illness, and climate, which has allowed organisms to flourish and procreate in a variety of ecological niches. With an emphasis on their function in human evolution, this study explores the molecular mechanisms underlying epigenetic control and how epigenetics allows humans to display amazing phenotypic plasticity. The ramifications of epigenetic studies in anthropology are also examined, with a focus on how modern humans differ from their hominid ancestors and how epigenetics influences cultural and social practices. This review further highlights the revolutionary potential of epigenetics in deciphering the intricacies of human evolution by fusing knowledge from genetics, anthropology, and environmental studies.

Generalized functional varying-index coefficient model for dynamic synergistic gene-environment interactions with binary longitudinal traits.

The genetic basis of complex traits involves the function of many genes with small effects as well as complex gene-gene and gene-environment interactions. As one of the major players in complex diseases, the role of gene-environment interactions has been increasingly recognized. Motivated by epidemiology studies to evaluate the joint effect of environmental mixtures, we developed a functional varying-index coefficient model (FVICM) to assess the combined effect of environmental mixtures and their interactions with genes, under a longitudinal design with quantitative traits. Built upon the previous work, we extend the FVICM model to accommodate binary longitudinal traits through the development of a generalized functional varying-index coefficient model (gFVICM). This model examines how the genetic effects on a disease trait are nonlinearly influenced by a combination of environmental factors. We derive an estimation procedure for the varying-index coefficient functions using quadratic inference functions combined with penalized splines. A hypothesis testing procedure is proposed to evaluate the significance of the nonparametric index functions. Extensive Monte Carlo simulations are conducted to evaluate the performance of the method under finite samples. The utility of the method is further demonstrated through a case study with a pain sensitivity dataset. SNPs were found to have their effects on blood pressure nonlinearly influenced by a combination of environmental factors.

FAM43A coordinates mtDNA replication and mitochondrial biogenesis in response to mtDNA depletion.

Mitochondrial retrograde signaling (MRS) pathways relay the functional status of mitochondria to elicit homeostatic or adaptive changes in nuclear gene expression. Budding yeast have "intergenomic signaling" pathways that sense the amount of mitochondrial DNA (mtDNA) independently of oxidative phosphorylation (OXPHOS), the primary function of genes encoded by mtDNA. However, MRS pathways that sense the amount of mtDNA in mammalian cells remain poorly understood. We found that mtDNA-depleted IMR90 cells can sustain OXPHOS for a significant amount of time, providing a robust model system to interrogate human intergenomic signaling. We identified FAM43A, a largely uncharacterized protein, as a CHK2-dependent early responder to mtDNA depletion. Depletion of FAM43A activates a mitochondrial biogenesis program, resulting in an increase in mitochondrial mass and mtDNA copy number via CHK2-mediated upregulation of the p53R2 form of ribonucleotide reductase. We propose that FAM43A performs a checkpoint-like function to limit mitochondrial biogenesis and turnover under conditions of mtDNA depletion or replication stress.

Motility genes are associated with the occurrence of Drosophila melanogaster-associated gut microbes

Abstract Recent work highlighted the role of motility genes in dispersing fly-associated microbes and their spread between hosts. We investigated whether bacterial genes encoding motility are associated with the occurrence of bacteria above passive dispersal levels in the gut of wild Drosophila melanogaster. We revisited 16S amplicon and shotgun metagenome data of wild flies and correlated four genera of bacteria (Commensalibacter, Gluconobacter, Lactobacillus, and Tatumella) with motility genes. We plotted the microbes against neutral models of ecological drift and passive dispersal. Microbes with positive correlations to motility were exclusively found at or above neutral model predictions, suggesting motility genes are crucial for fly microbiota spread and colonization. This information is crucial for understanding how specific gene functions contribute to microbial community dispersal and colonization within the fly host. Moreover, this study’s findings serve as a proof of concept for using the neutral model to predict microbial functions essential for survival and dissemination in diverse hosts.

A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries. This perturbation atlas comprises high-dimensional phenotypic profiles of individual cells with sufficient resolution to cluster thousands of human genes, reconstruct known pathways and protein-protein interaction networks, interrogate subcellular processes and identify culture media-specific responses. Using this atlas, we identify the poorly characterized disease-associated TMEM251/LYSET as a Golgi-resident transmembrane protein essential for mannose-6-phosphate-dependent trafficking of lysosomal enzymes. In sum, this perturbation atlas and screening platform represents a rich and accessible resource for connecting genes to cellular functions at scale.

Genomic evidence for demographic fluctuations, genetic burdens and adaptive divergence in fourfinger threadfin Eleutheronema rhadinum

Abstract Declining populations and bottlenecks lead to the accumulation of deleterious mutations in fish populations. These processes also trigger genetic purging, which is a key genetic factor in reducing the deleterious burdens and increasing population viability. However, there is a lack of empirical evidence on the interaction between demographic history and the genome-wide pattern of deleterious variations. Here, we generated genome resequencing data of Eleutheronema rhadinum from China and Thailand, representing the major distribution of the species’ southern regions. E. rhadinum had exceptionally low genome-wide variability and experienced dramatic population expansions followed by continuous declines. The geographical divergence, which occurred ~ 23,000 years ago, shaped different demographic trajectories and generated different regional patterns of deleterious mutations in China and Thailand populations. Several lines of evidence revealed that this geographical pattern of deleterious mutation was driven by the purging of highly deleterious mutations. We showed that purifying selection had inbreeding-associated fitness costs and was more efficient against missense mutations in the Thailand population, which had the lowest genetic burden of homozygous deleterious mutations. Multiple evolutionarily conserved protein domains were disrupted by the loss-of-function mutations, posing a high probability of gene functionality elimination. Moreover, thermal and salinity genes (Trpm3, Nek4, Gtf2f2, Cldn14) were identified in genomic divergence regions of E. rhadinum among China and Thailand populations. Our findings highlight the importance of demographic history factors shaping the geographical patterns of deleterious mutations. The results serve to deepen our understanding of the adaptive evolution and divergence of E. rhadinum with implications for other marine fish.

Comparative transcriptome and metabolome analysis reveals the differential response to salinity stress of two genotypes brewing sorghum

Salinity tolerance in brewing sorghum is a very important trait, especially in areas that are affected by soil salinity. In order to elucidate the mechanism underlying salt tolerance, we conducted a comparative analysis of the transcriptome and metabolome in two distinct sweet sorghum genotypes, namely the salt-tolerant line NY1298 and the salt-sensitive line MY1176, following exposure to salt treatment. Our initial findings indicate the presence of genotype-specific responses in brewing sorghum under salt stress conditions. Notably, there were variations in the expression of genes and metabolites among different genotypes in response to high-salt stress. Specifically, certain transcription factors belonging to the WRKY, MYB, and NAC families were identified as being involved in the response to increased external salinity. WGCNA analysis identified stage-specific gene expression for different salinity gradients in each cultivar, and explored the gene function by KEGG enrichment analysis. Combined analysis of DEGs and DEMs in hormone synthesis found AUX/IAA, SAUR, CRE1, A-ARR, PP2C, SNRK2 genes, and 3-indoleacetic acid and jasmonic acid were evidently differential expression among different salt concentrations. Taken together, our study carried out a comprehensive overview of two genotypes of brewing sorghum gene and metabolite expression differences in response to salt stress, and expanded the understanding of responsive mechanism of brewing sorghum to salt stress.

Massive gene loss in the fungus Sporothrix epigloea accompanied a shift to life in a glucuronoxylomannan-based gel matrix.

Fungi are well known for their ability to both produce and catabolize complex carbohydrates to acquire carbon, often in the most extreme of environments. Glucuronoxylomannan (GXM)-based gel matrices are widely produced by fungi in nature and though they are of key interest in medicine and pharmaceuticals, their biodegradation is poorly understood. Though some organisms, including other fungi, are adapted to life in and on GXM-like matrices in nature, they are almost entirely unstudied, and it is unknown if they are involved in matrix degradation. Sporothrix epigloea is an ascomycete fungus that completes its life cycle entirely in the short-lived secreted polysaccharide matrix of a white jelly fungus, Tremella fuciformis. To gain insight into how S. epigloea adapted to life in this unusual microhabitat, we compared the predicted protein composition of S. epigloea to that of 21 other Sporothrix species. We found that the genome of S. epigloea is smaller than that of any other sampled Sporothrix, with widespread functional gene loss, including those coding for serine proteases and biotin synthesis. In addition, many predicted CAZymes degrading both plant and fungal cell wall components were lost while a lytic polysaccharide monooxygenase (LPMO) with no previously established activity or substrate specificity, appears to have been gained. Phenotype assays suggest narrow use of mannans and other oligosaccharides as carbon sources. Taken together, the results suggest a streamlined machinery, including potential carbon sourcing from GXM building blocks, facilitates the hyperspecialized ecology of S. epigloea in the GXM-like milieu.

Evaluation of the Role of PnuC Gene in Enhancing Nicotinamide Mononucleotide Synthesis.

The PnuC gene plays a crucial role in the complex processes related to the absorption and synthesis of the nicotinamide mononucleotide (NMN) precursor. NMN, a nicotinamide adenine dinucleotide (NAD+) precursor, is important for cellular energy metabolism, DNA repair, and antiaging. This study focuses on elucidating the precursor absorption mechanism and the specific function of the PnuC gene in encoding membrane transport proteins, as well as its impact on the regulation and dynamics of NMN within the cell. This understanding aims to provide insights into its potential effects on metabolic balance, illustrated through two NAD+ biosynthesis pathways based on renewable and readily available cytoplasmic resources, assessing the potential of PnuC gene expression in clarifying complex interactions within regulation mechanisms. Enhanced expression analysis of the PnuC gene has initiated discussions on its potential applications in treating aging-related diseases and dysfunctions, contributing to cellular health maintenance.

Effect of Temperature on Polyamine Oxidase Genes in Skeletonema dohrnii

In our experiments, we investigated the effect of temperature on diatom polyamine metabolism using Skeletonema dohrnii as an experimental algal species. We set three different temperature conditions for incubation and selected Skeletonema dohrnii in the exponential growth period, and analyzed basic physiological parameters, polyamine composition and content, and polyamine oxidase (PAO) gene expression at different temperatures. The results showed that low temperatures led to a decrease in growth rate, an increase in biogenic silica content, an increase in the content of putrescine and spermine, a decrease in the concentration of spermidine, and a down-regulation of PAO gene expression. In addition, high temperature led to an increase in growth rate, a significant change in the concentration of putrescine and spermine, and an increase in spermidine. These findings suggest that changes in temperature affect the growth rate of algae, low temperature increases the biogenic silica content of diatoms, different temperature stresses lead to different kinds of polyamine changes in diatoms, and the PAO gene may play a role in regulating the response of algae to temperature changes. This study lays a foundation for further exploration of the function of the PAO gene in Skeletonema dohrnii.

MicroRNA‐microbiota interactions: Emerging strategies for modulating intestinal homeostasis and enhancing host health

AbstractLong‐term artificial selection and environmental shifts have driven adaptive changes in both the host genome and the intestinal microbiota. The complex symbiotic relationship between these two has become essential for maintaining intestinal homeostasis and overall health. Concurrently, advancements in sequencing technology and the functional annotation of noncoding RNAs, particularly microRNAs (miRNAs), have facilitated the exploration of mechanisms regulating intestinal homeostasis. Herein, we systematically update the role of miRNA–microbiota interactions in regulating the intestinal barrier, intestinal immunity, changes in intestinal microbiota dynamics, and maintenance of intestinal homeostasis, and we further critically discuss the role of miRNA–microbiota interactions in the maintenance of host intestinal health, metabolic regularity, brain function, and neurodegenerative disease‐related disorders. Finally, we highlight the prospects and therapeutic strategies regarding miRNA–microbiota interactions in humans and animals in the context of intestinal microbiota and gene function studies. This study provides a comprehensive overview of miRNA–microbiota interactions and their influence on intestinal homeostasis and host health and offers novel therapeutic strategies for future personalized prevention and treatment of intestinal diseases.

Doubletrouble: an R/Bioconductor package for the identification, classification, and analysis of gene and genome duplications.

Gene and genome duplications are major evolutionary forces that shape the diversity and complexity of life. However, different duplication modes have distinct impacts on gene function, expression, and regulation. Existing tools for identifying and classifying duplicated genes are either outdated or not user-friendly. Here, we present doubletrouble, an R/Bioconductor package that provides a comprehensive and robust framework for analyzing duplicated genes from genomic data. doubletrouble can detect and classify gene pairs as derived from six duplication modes (segmental, tandem, proximal, retrotransposon-derived, DNA transposon-derived, and dispersed duplications), calculate substitution rates, detect signatures of putative whole-genome duplication events, and visualize results as publication-ready figures. We applied doubletrouble to classify the duplicated gene repertoire in 822 eukaryotic genomes, and results were made available through a user-friendly web interface. doubletrouble is available on Bioconductor (https://bioconductor.org/packages/doubletrouble), and the source code is available in a GitHub repository (https://github.com/almeidasilvaf/doubletrouble). doubletroubledb is available online at https://almeidasilvaf.github.io/doubletroubledb/. Supplementary data are available at Bioinformatics online and at https://github.com/almeidasilvaf/doubletrouble_paper.

Edaphic factors mediate the response of nitrogen cycling and related enzymatic activities and functional genes to heavy metals: A review.

Soil nitrogen (N) transformations control N availability and plant production and pose environmental concerns when N is lost, raising issues such as soil acidification, water contamination, and climate change. Former studies suggested that soil N cycling is chiefly regulated by microbial activity; however, emerging evidence indicates that this regulation is disrupted by heavy metal (HM) contamination, which alters microbial communities and enzyme functions critical to N transformations. Environmental factors like soil organic carbon, soil texture, water content, temperature, soil pH, N fertilization, and redox status play significant roles in modulating the response of soil N cycling to HM contamination. This review examines how different HMs affect soil N processes, including N fixation, mineralization, nitrification, denitrification, dissimilatory nitrate reduction to ammonium (DNRA), and immobilization, as well as microbial activities and functional genes related to soil N transformations. The review additionally outlines the impact of HMs on environmental degradation, including the risk of soil N losses (e.g., leaching, runoff, and gaseous emissions) and depletion of soil fertility, thus threatening the sustainability of the ecosystem. The effect of edaphic factors and fertilization on soil N cycling response to HM contamination was also examined. The effect of phytoremediation, a sustainable approach to remediate HM polluted soils, on N cycling was also reviewed. Thus, this review underscores the importance of increasing research and innovative strategies to combat HM pollution's effects to enhance soil health, boost crop yields, and protect soil stability and productivity.

Shifts in fungal communities drive soil profile nutrient cycling during grassland restoration.

Soil microbial diversity and community life strategies are crucial for nutrient cycling during vegetation restoration. Although the changes in topsoil microbial communities during restoration have been extensively studied, the structure, life strategies, and function of microbial communities in the subsoil remain poorly understood, especially regarding their role in nutrient cycling during vegetation restoration. In this study, we conducted a comprehensive investigation of the changes in the soil microbial community, assembly process, life strategies, and nutrient cycling functional genes in soil profiles (0-100 cm) across a 36 year chronosequence (5, 15, 28, and 36 years) of fenced grassland and one grazing grassland on the Loess Plateau of China. Our results revealed that soil organic carbon increased by 76.0% in topsoil and 91.6% in subsoil after 36 years of restoration. The bacterial communities were influenced primarily by soil depth, while the fungal communities were highly sensitive to the years of restoration. Microbes in the subsoil recovered faster, and the microbial community structure and functional genes in the soil profiles gradually became more consistent following restoration. In addition, we observed a transition in microbial life history strategies from a persistent K-strategy to a rapid r-strategy during restoration. Notably, the fungal community assembly process played an important role in changes in nutrient cycling genes, which were accompanied by increased carbon fixation and nitrogen mineralization function. Overall, our findings provide several novel insights into the impact of changes in the fungal community on soil nutrient cycling in the soil profile during vegetation restoration.IMPORTANCEOur study revealed that microbes in the subsoil recovered faster than those in the topsoil, which contributed to the reduction in differences in microbial community structure and the distribution of functional genes throughout the soil profile during the restoration process. Importantly, the assembly of fungal communities plays a pivotal role in driving changes in nutrient cycling genes, such as increased carbon fixation and nitrogen mineralization, alongside a reduction in carbon degradation gene abundance. These alterations increase soil organic carbon and nutrient availability during restoration. Our results increase the understanding of the critical role of fungal communities in soil nutrient cycling genes, which facilitate nutrient accumulation in soil profiles during grassland restoration. This insight can guide the development of strategies for manipulating fungal communities to increase soil nutrients in grasslands.

Disulfidptosis-related gene SLC3A2: a novel prognostic biomarker in nasopharyngeal carcinoma and head and neck squamous cell carcinoma

IntroductionNasopharyngeal carcinoma (NPC), one of the most common malignancies of the head and neck, is characterised by a complex pathogenesis and an unfavourable prognosis. Recently, disulfidoptosis, a novel form of cell death, has been proposed. Several studies in recent years have extensively investigated the function of the disulfidoptosis-related SLC7A11 gene in cancer, but the role of its partner protein, SLC3A2, remains unknown unclear in NPC.MethodsGEO database analysis confirmed SLC3A2's prognostic impact on nasopharyngeal carcinoma. ROC, Kaplan-Meier analyses, and stage-specific expression studies showed a strong correlation with poor HNSC prognosis. GO and KEGG analyses pinpointed relevant signaling pathways. In vitro, SLC3A2's influence on cell proliferation, migration, and invasion was evaluated through CCK8, wound healing, colony formation, transwell assays, and cell cycle analysis.ResultsIn this study, we identified the high expression of SLC3A2 in NPC and head and neck squamous cell carcinoma (HNSC) and analyzed its potential mechanism and correlation with patient prognosis. Furthermore, a negative relationship was found between the expression level of SLC3A2 and the extent of immune cell infiltration and immune checkpoint. Differentially expressed genes (DEGs) between the high and low SLC3A2 expression groups were primarily involved in cytokine-cytokine receptor interaction and immune response. Finally, in vitro experiments demonstrated that SLC3A2 stimulates tumor cell proliferation and migration. DiscussionIn conclusion, these results indicated a strong association between SLC3A2 and progression in both NPC and HNSC, suggesting it as a promising biomarker for predicting adverse prognosis in NPC and HNSC patients.

Whole-genome resequencing landscape of adaptive evolution in Relict gull (Larus relictus)

BackgroundThe relict gull (Larus relictus, Charadriiformes, Laridae) classified as vulnerable in the IUCN Red List is defined as a first-class national protected bird in China. However, our knowledge of the evolutionary history of L. relictus is limited. Here, we performed whole-genome resequencing of L. relictus (n = 14) and L. brunnicephalus (n = 3) to explore the genetic relationships and population structures and understand their adaptive evolution.ResultsThe whole genome resequencing generated 667.55 Gb clean reads with an average sequencing depth of ~ 29×. The genomic variant analysis identified 13,717,267 heterozygous SNPs in the samples obtained from 17 individuals. Population genetic diversity analysis revealed that low nucleotide diversity (0.00029) and no obvious population structure in L. relictus. Demographic history revealed that from 180 to 5 kya (thousand years ago), the effective population size (Ne) of L. relictus exhibited declines (24,000 to 5,000), with a very low range population size (2,200 to 5,000). In contrast, from 100 to 80 kya, L. brunnicephalus peaked in ancestral Ne, followed by distinct declines at ~ 70 kya (100,000 to 16,000). The findings identified several genes associated with the correlated changed life-history traits of L. relictus, including BMP4 involved in beak adaptation; HAND2, NEUROG1, COL11A2, and EDNRB involved in the evolution of the palate, soft palate, and tongue; PIGR and PLCB2 involved in an enhanced response to bitter taste by sensing chemical secretions released by staple food substrate insects to activate protective mechanisms. Furthermore, thirty-four genes related to sperm development and activity, including KLHL10 and TEKT3, were identified in the expanded gene family. In addition, MED1, CNOT9, NR5A1, and PATZ1 were involved in enhanced male hormone secretion and a high density of candidate genes associated with embryonic development were identified. The findings indicated that the L. relictus population was in a male-biased diffusion mode; the function of the TEKT3 gene showed that males played a dominant role in brooding, which enhanced their attraction to females. Our study revealed that significant enrichment of olfactory signaling pathway genes, including OR14C36, OR14J1, OR14I1, and OR14A16; inner ear development-related, including PTN, PTPN11, GATA2, ATP8B1, and MYO15A; and those related to hypoxic adaptation to high-altitude breeding and iris colour.ConclusionsBased on the results and the knowledge of this organism biology and habitat use, we infer that less adaptive evolutionary pressure on vision in L. relictus were related with their feeding behaviour and adaptation. In summary, this comprehensive analysis provides insights into the evolutionary features of L. relictus and a new perspective for scientific research on L. relictus to effectively determine its future survival viability.

Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology.

Sex chromosomes are a fundamental aspect of sex-biased biology, but the extent to which homologous X-Y gene pairs ('the gametologs') contribute to sex-biased phenotypes remains hotly debated. Although these genes tend to exhibit large sex differences in expression throughout the body (XX females can express both X members, and XY males can express one X and one Y member), there is conflicting evidence regarding the degree of functional divergence between the X and Y members. Here we develop and apply co-expression fingerprint analysis to characterize functional divergence between the X and Y members of 17 gametolog gene pairs across >40 human tissues. Gametolog pairs exhibit functional divergence between the sexes that is driven by divergence between the X versus Y members (assayed in males), and this within-pair divergence is greatest among pairs with evolutionarily distant X and Y members. These patterns reflect that X versus Y gametologs show coordinated patterns of asymmetric coupling with large sets of autosomal genes, which are enriched for functional pathways and gene sets implicated in sex-biased biology and disease. Our findings suggest that the X versus Y gametologs have diverged in function and prioritize specific gametolog pairs for future targeted experimental studies.

ZNF165: A Pan-Cancer Biomarker with Prognostic and Therapeutic Potential.

The role of ZNF165 in only a few tumors has been reported. ZNF165 plays an important role in liver cancer, gastric cancer, and breast cancer, especially in regulating the immune microenvironment, promoting tumor cell proliferation and migration, and serving as a potential target for immunotherapy. This study aimed to enhance an understanding of how the ZNF165 gene functions and influences cancer development. Using a suite of online resources, including TIMER, TCGA, GTEx, GEPIA2, cBioPortal, TIMER2, STRING, DAVID, RNAactDrug, CancerSEA, and UCSC, along with comprehensive statistical analyses, we conducted a thorough investigation of the pan-cancer landscape of ZNF165. This study encompassed an assessment of ZNF165 levels, their associations with patient outcomes, and clinical correlates. We examined the interplay between ZNF165 and key cancer biomarkers, such as Microsatellite Instability (MSI), Tumor Mutational Burden (TMB), immune cell infiltration, and the expression of immune checkpoint genes. We delved into the genetic variations of ZNF165, its biological roles across various cancer types, and its potential links to drug responsiveness. We analyzed single-cell expression patterns of ZNF165 and their implications for the functional dynamics of cancer. We employed quantitative Reverse Transcription PCR (qRT-PCR) to measure ZNF165 levels in Ovarian Cancer (OC) cell lines. ZNF165 expression displayed aberrations across a diverse range of human cancers and exhibited correlations with clinical stages. High ZNF165 expression in KIRC, KIRP, STAD, and UCEC was significantly associated with poor overall survival. ZNF165 has encouraging diagnostic value in specific tumor types, with gene amplification identified as the predominant genetic alteration. Our analysis further uncovered significant associations between ZNF165 levels and MSI across three distinct cancer types, as well as with TMB in six different malignancies. We detected substantial correlations between ZNF165 levels and immune cell infiltration, as well as the expression of immune checkpoint genes. ZNF165 was found to be involved in several prevalent signaling pathways across various cancer types. ZNF165 may potentially contribute to chemotherapy and chemoresistance, and was observed to be involved in cancer progression. A ceRNA regulatory network involving AFDN-DT, miR-191-5p, and ZNF165 was constructed for OC, revealing significantly elevated ZNF165 levels in OC cell lines. Dysregulated ZNF165 expression across a spectrum of malignancies might play a role in cancer initiation and advancement via multiple biological pathways. ZNF165 may serve as a promising therapeutic target for the treatment of cancer in human patients.

Exploring markers in nursing care of prostate cancer.

Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis, protein-protein interaction analysis, gene function enrichment analysis, and comparative toxicology database analysis. Finally, the gene expression heat map was drawn, and miRNA information regulating core DEGs was retrieved. A total of 1151 DEGs were found, most of them focusing on systematic development, cell development, cell differentiation, regulation of multicellular biological processes, anatomical morphogenesis, MAPK signaling pathway, proteoglycans in cancer, fluid shear stress, and atherosclerosis. The core genes (MYL9, TAGLN, SMTN, CNN1, MYH11, MYLK, MYOCD, ACTC1, LMOD1, and TPM2) obtained in end are all lowly expressed in prostate cancer samples and are associated with hypertension, tumor metastasis, prostate tumors, and tumor aggressiveness. LMOD1 and SMTN are lowly expressed in prostate cancer and may be used as markers in prostate cancer nursing.