Influence Gene Expression Research Articles

The role of exogenous hydrogen sulfide in mitigating cadmium toxicity in plants: A comprehensive meta-analysis.

Reducing the accumulation of cadmium (Cd) and mitigating its toxicity are pivotal strategies for addressing Cd pollution's threats to agriculture and human health. Hydrogen sulfide (H2S) serves as a signaling molecule, playing a crucial role in plant stress defense mechanisms. Nevertheless, a comprehensive assessment of the impact of exogenous H2S on plant growth, antioxidant properties, and gene expression under Cd stress remains lacking. In this meta-analysis, we synthesized 575 observations from 27 articles, revealing that exogenous H2S significantly alleviates Cd-induced growth inhibition in plants. Specifically, it enhances root length (by 8.71%), plant height (by 15.67%), fresh weight (by 15.15%), dry weight (by 22.54%), and chlorophyll content (by 27.99%) under Cd stress conditions. H2S boosts antioxidant enzyme activity, particularly catalase (CAT), by 39.51%, thereby reducing Cd-induced reactive oxygen species (ROS) accumulation. Moreover, it impedes Cd translocation from roots to shoots, resulting in a substantial 40.19% reduction in stem Cd content. Additionally, H2S influences gene expression in pathways associated with antioxidant enzymes, metal transport, heavy metal tolerance, H2S biosynthesis, and energy metabolism. However, the efficacy of exogenous H2S in alleviating Cd toxicity varies depending on factors such as plant species, concentration of the H2S donor sodium hydrosulfide (NaHS), application method, and cultivation techniques. Notably, NaHS concentrations exceeding 200 μM may adversely affect plants. Overall, our study underscores the role of exogenous H2S in mitigating Cd toxicity and elucidates its mechanism, providing insights for utilizing H2S to combat Cd pollution in agriculture.

Coadministration of doxorubicin with vitamin D3, Lactobacillus acidophilus, and Lactobacillus casei in the 4T1 mouse model of breast cancer: anticancer and enteroprotective effects.

The use of doxorubicin (Dox) in the treatment of breast cancer negatively affects the intestines and other tissues. Many studies have proven that probiotics and vitamin D3 have antitumor and intestinal tissue-protecting properties. To achieve effectiveness and minimize side effects, the current study aims to administer Dox together with probiotics (Lactobacillus acidophilus and Lactobacillus casei) and vitamin D3. Forty-two female BALB/c inbred mice were divided into six groups: Group 1 (Control), Group 2 (Dox), Group 3 (Dox and probiotics), Group 4 (Dox and vitamin D3), Group 5 (Dox, probiotics, and vitamin D3), and Group 6 (probiotics and vitamin D3). The 4T1 mouse carcinoma cell line was injected into the mammary fat pad of each mouse. Gene expression was examined using quantitative real-time PCR. The treated groups (except group 6) showed significantly reduced tumor volume and weight compared to the control group (P < 0.05, P < 0.01). Probiotics/vitamin D3 with Dox reduced chemotherapy toxicity and a combination of supplements had a significant protective effect against Dox (P < 0.05, 0.01, 0.001). The treated groups (except 6) had significantly higher expression of Bax/Caspase 3 genes and lower expression of Bcl-2 genes than the control group (P < 0.05, 0.01). Coadministration of Dox with probiotics and vitamin D3 showed promising results in reducing tumor size, protecting intestinal tissue and influencing gene expression, suggesting a strategy to enhance the effectiveness of breast cancer treatment while reducing side effects.

The role of human 5-Lipoxygenase (5-LO) in carcinogenesis - a question of canonical and non-canonical functions.

5-Lipoxygenase (5-LO), a fatty acid oxygenase, is the central enzyme in leukotriene (LT) biosynthesis, potent arachidonic acid-derived lipid mediators released by innate immune cells, that control inflammatory and allergic responses. In addition, through interaction with 12- and 15-lipoxgenases, the enzyme is involved in the formation of omega-3 fatty acid-based oxylipins, which are thought to be involved in the resolution of inflammation. The expression of 5-LO is frequently deregulated in solid and liquid tumors, and there is strong evidence that the enzyme plays an important role in carcinogenesis. However, global inhibition of LT formation and signaling has not yet shown the desired success in clinical trials. Curiously, the release of 5-LO-derived lipid mediators from tumor cells is often low, and the exact mechanism by which 5-LO influences tumor cell function is poorly understood. Recent data now show that in addition to releasing oxylipins, 5-LO can also influence gene expression in a lipid mediator-independent manner. These non-canonical functions, including modulation of miRNA processing and transcription factor shuttling, most likely influence cancer cell function and the tumor microenvironment and might explain the low clinical efficacy of pharmacological strategies that previously only targeted oxylipin formation and signaling by 5-LO. This review summarizes the canonical and non-canonical functions of 5-LO with a particular focus on tumorigenesis, highlights unresolved issues, and suggests future research directions.

Omics-based construction of regulatory variants can be applied to help decipher pig liver-related traits

Genetic variants can influence complex traits by altering gene expression through changes to regulatory elements. However, the genetic variants that affect the activity of regulatory elements in pigs are largely unknown, and the extent to which these variants influence gene expression and contribute to the understanding of complex phenotypes remains unclear. Here, we annotate 90,991 high-quality regulatory elements using acetylation of histone H3 on lysine 27 (H3K27ac) ChIP-seq of 292 pig livers. Combined with genome resequencing and RNA-seq data, we identify 28,425 H3K27ac quantitative trait loci (acQTLs) and 12,250 expression quantitative trait loci (eQTLs). Through the allelic imbalance analysis, we validate two causative acQTL variants in independent datasets. We observe substantial sharing of genetic controls between gene expression and H3K27ac, particularly within promoters. We infer that 46% of H3K27ac exhibit a concomitant rather than causative relationship with gene expression. By integrating GWAS, eQTLs, acQTLs, and transcription factor binding prediction, we further demonstrate their application, through metabolites dulcitol, phosphatidylcholine (PC) (16:0/16:0) and published phenotypes, in identifying likely causal variants and genes, and discovering sub-threshold GWAS loci. We provide insight into the relationship between regulatory elements and gene expression, and the genetic foundation for dissecting the molecular mechanism of phenotypes.

Phytocompounds targeting epigenetic modulations: an assessment in cancer.

For centuries, plants have been serving as sources of potential therapeutic agents. In recent years, there has been a growing interest in investigating the effects of plant-derived compounds on epigenetic processes, a novel and captivating Frontier in the field of epigenetics research. Epigenetic changes encompass modifications to DNA, histones, and microRNAs that can influence gene expression. Aberrant epigenetic changes can perturb key cellular processes, including cell cycle control, intercellular communication, DNA repair, inflammation, stress response, and apoptosis. Such disruptions can contribute to cancer development by altering the expression of genes involved in tumorigenesis. However, these modifications are reversible, offering a unique avenue for therapeutic intervention. Plant secondary compounds, including terpenes, phenolics, terpenoids, and sulfur-containing compounds are widely found in grains, vegetables, spices, fruits, and medicinal plants. Numerous plant-derived compounds have demonstrated the potential to target these abnormal epigenetic modifications, including apigenin (histone acetylation), berberine (DNA methylation), curcumin (histone acetylation and epi-miRs), genistein (histone acetylation and DNA methylation), lycopene (epi-miRs), quercetin (DNA methylation and epi-miRs), etc. This comprehensive review highlights these abnormal epigenetic alterations and discusses the promising efficacy of plant-derived compounds in mitigating these deleterious epigenetic signatures in human cancer. Furthermore, it addresses ongoing clinical investigations to evaluate the therapeutic potential of these phytocompounds in cancer treatment, along with their limitations and challenges.

Abstract 3226: PRMT1 is a critical dependency in clear cell renal cell carcinoma with roles in post- transcriptional regulation and DNA damage response

Abstract The majority of sporadic renal cell carcinoma (RCC) cases present as the clear cell subtype (ccRCC) and are associated with the biallelic inactivation of the von Hippel-Lindau (VHL) gene, leading to constitutive activation of the cellular hypoxia response and deleterious alterations to gene expression, metabolism, and growth. Despite the near ubiquity of VHL loss, evidence suggests that it alone is insufficient to drive tumor establishment. Additional loss of function (LOF) mutations in epigenetic regulatory proteins including PBRM1, SETD2 and BAP1 have been identified as tumor drivers. The frequency and penetrance of these mutations in epigenetic regulators implicates a vulnerability in ccRCC that may be exploited to develop new therapies. To explore this vulnerability, the Ailles lab completed a screen of the Structural Genomics Consortium’s (SGC) epiprobe library - a panel of inhibitors targeting an array of epigenetic regulators in patient derived ccRCC models. Among the several promising targets identified, a particularly favorable inhibition profile was noted for MS023, an inhibitor of the type I protein arginine methyltransferase family (PRMT1/3/4/6 and 8). PRMTs transfer methyl groups to nuclear histones and cytoplasmic targets, influencing gene expression, mRNA processing and viability. This growth inhibition was corroborated using an additional type I PRMT compound, GSK3368715. CRISPR-mediated deletion of type I PRMT targets indicated that PRMT1 is the main enzyme responsible for growth inhibition in our ccRCC models. Furthermore, genetic depletion of PRMT1 via shRNA phenocopied pharmacological inhibition and proliferative growth was restored in the presence of MS023 by overexpressing PRMT1. Finally, MS023 treatment of mice bearing ccRCC cell line and patient derived xenografts led to significant inhibition of tumor growth in vivo. Transcriptomic profiling of chemical treatment and PRMT1 genetic depletion demonstrated that PRMT1 inhibition triggers a significant down regulation of genes related to cell cycle progression and DNA damage. ccRCC cells treated with MS023 accumulated significant levels of DNA damage before undergoing cell death, with several DDR-related proteins being down-regulated. Proximity ligation and proteomic analysis (Bio-ID) revealed that PRMT1’s interactors skew heavily towards RNA metabolism regulators and widespread alterations in mRNA processing were noted with MS023 treatment. Evidence continues to mount that PRMT1 is implicated in the biology of cancer, but to our knowledge, no thorough investigations have been performed in the context of ccRCC. Our data suggests that inhibition of PRMT1 inhibits processing of mRNA transcripts, compromises DDR mechanisms, leading to an accumulation of double stranded breaks, cytostasis and cell death. Thus PRMT1 represents a viable therapeutic target in ccRCC. Citation Format: Joseph Walton, Karen Arevalo, Angel SN Ng, Jalna Meens, Christina Karamboulas, Panagiotis Prinos, Brian Raught, Eric Chen, Cheryl Arrowsmith, Laurie Ailles. PRMT1 is a critical dependency in clear cell renal cell carcinoma with roles in post- transcriptional regulation and DNA damage response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3226.

N-Acetylcysteine Alleviates D-Galactose-Induced Injury of Ovarian Granulosa Cells in Female Rabbits by Regulating the PI3K/Akt/mTOR Signaling Pathway

The ovary plays a crucial role in the reproductive system of female animals. Ovarian problems such as ovarian insufficiency, premature aging, polycystic ovary syndrome, and ovarian cysts may lead to ovulation disorders, abnormal hormone secretion, or luteal dysfunction, thereby increasing the risk of infertility and abortion. Only when the ovarian function and other organs in the reproductive system remain healthy and work normally can female animals be ensured to carry out reproductive activities regularly, improve the pregnancy rate and litter size, promote the healthy development of the fetus, and then improve their economic value. The follicle, as the functional unit of the ovary, is composed of theca cells, granulosa cells (GCs), and oocytes. GCs are the largest cell population and main functional unit in follicles and provide the necessary nutrients for the growth and development of follicles. N-acetylcysteine (NAC) is a prevalent and cell-permeable antioxidant molecule that effectively prevents apoptosis and promotes cellular survival. Over the past few years, its function in boosting reproductive performance in animals at the cellular level has been widely acknowledged. However, its specific role and mechanism in influencing GCs is yet to be fully understood. The objective of this study was to examine the effects of NAC on ovarian damage in female rabbits. For this purpose, D-galactose (D-gal) was first used to establish a model of damaged GCs, with exposure to 1.5 mg/mL of D-gal leading to substantial damage. Subsequently, varying concentrations of NAC were introduced to determine the precise mechanism through which it influences cell damage. Based on the results of the Cell Counting Kit-8 assay, flow cytometry, and Western blotting, it was found that 0.5 mg/mL of NAC could significantly suppress cell apoptosis and promote proliferation. In particular, it decreased the expression levels of Bax, p53, and Caspase-9 genes, while concurrently upregulating the expression of the BCL-2 gene. Moreover, NAC was found to alleviate intracellular oxidative stress, suppress the discharge of mitochondrial Cytochrome c, and boost the enzymatic activities of CAT (Catalase), GSH (Glutathione), and SOD (Superoxide dismutase). RNA sequencing analysis subsequently underscored the critical role of the PI3K/Akt/mTOR pathway in governing proliferation and apoptosis within GCs. These findings demonstrated that NAC could significantly influence gene expression within this pathway, thereby clarifying the exact relationship between the PI3K/Akt/mTOR signaling cascade and the underlying cellular processes controlling proliferation and apoptosis. In conclusion, NAC can reduce the expression of Bax, p53, and Caspase-9 genes, inhibit the apoptosis of GCs, improve cell viability, and resist D-gal-induced oxidative stress by increasing the activity of CAT, GSH, and SOD. The molecular mechanism of NAC in alleviating D-gal-induced ovarian GC injury in female rabbits by regulating the PI3K/Akt/mTOR signaling pathway provides experimental evidence for the effect of NAC on animal reproductive function at the cellular level.

Abstract 2946: Characterizing the genomic landscapes of breast and lung tumors using cost-effective whole genome sequencing

Abstract Whole Genome Sequencing (WGS) has emerged as a pivotal tool for unraveling the intricate genomic alterations underlying cancer, enabling the detection of a broad spectrum of somatic changes in cancer genomes, including single nucleotide variants, insertions, deletions, copy number variations, and structural rearrangements. Characterizing somatic variants across the entire genome significantly benefits from novel cost-efficient sequencing platforms, such as UG100. In the current study, we aim to demonstrate the utility of UG100 WGS in characterizing the landscape of somatic events in breast and lung cancer. Over 35 tumor-normal cancer sample pairs were profiled using UG100 WGS (mean tumor coverage: &amp;gt;100x; normal: &amp;gt;50x). Variant calling was done using a somatic deep-variant algorithm, optimized to UG100 data. Results were compared to Illumina sequencing and high concordance was observed, with over 97% of SNVs and over 93% of indels detected by Illumina identified also by UG100. UG100 sequencing was deeper and allowed for identification of a larger number of genomic variations, including known driver events in cancer-related genes. The somatic mutational signatures by UG100 were concordant with the Illumina platform, with a cosine similarity higher than 99%. Copy number variation and structural variation analysis was performed on all sample pairs, revealing a wide range of genomic aberrations. The integration of genetic sequencing into routine clinical oncology practices has proven instrumental in identifying actionable mutations, predicting treatment responses, and monitoring minimal residual disease. Moving from targeted sequencing to WGS provides a more comprehensive and unbiased assessment of the entire genome, uncovering rare or unexpected mutations that might be missed by targeted approaches. WGS allows for the simultaneous evaluation of both coding and non-coding regions of the genome, providing a deeper understanding of the regulatory elements influencing gene expression. This broader scope enhances our understanding of cancer biology and contributes to a more accurate assessment of the tumor's functional landscape. Citation Format: Hila Benjamin, Ilya Soifer, Doron Shem-Tov, Maya Levy, Islam Oguz Tuncay, Baek-Lok Oh, Jong-Yeon Shin, Young Seok Ju, Sangmoon Lee, Omer Barad, Doron Lipson. Characterizing the genomic landscapes of breast and lung tumors using cost-effective whole genome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2946.

Sex and fetal genome influence gene expression in pig endometrium at the end of gestation

BackgroundA fine balance of feto-maternal resource allocation is required to support pregnancy, which depends on interactions between maternal and fetal genetic potential, maternal nutrition and environment, endometrial and placental functions. In particular, some imprinted genes have a role in regulating maternal-fetal nutrient exchange, but few have been documented in the endometrium. The aim of this study is to describe the expression of 42 genes, with parental expression, in the endometrium comparing two extreme breeds: Large White (LW); Meishan (MS) with contrasting neonatal mortality and maturity at two days of gestation (D90-D110). We investigated their potential contribution to fetal maturation exploring genes-fetal phenotypes relationships. Last, we hypothesized that the fetal genome and sex influence their endometrial expression. For this purpose, pure and reciprocally crossbred fetuses were produced using LW and MS breeds. Thus, in the same uterus, endometrial samples were associated with its purebred or crossbred fetuses.ResultsAmong the 22 differentially expressed genes (DEGs), 14 DEGs were differentially regulated between the two days of gestation. More gestational changes were described in LW (11 DEGs) than in MS (2 DEGs). Nine DEGs were differentially regulated between the two extreme breeds, highlighting differences in the regulation of endometrial angiogenesis, nutrient transport and energy metabolism. We identified DEGs that showed high correlations with indicators of fetal maturation, such as ponderal index at D90 and fetal blood fructose level and placental weight at D110.We pointed out for the first time the influence of fetal sex and genome on endometrial expression at D90, highlighting AMPD3, CITED1 and H19 genes. We demonstrated that fetal sex affects the expression of five imprinted genes in LW endometrium. Fetal genome influenced the expression of four genes in LW endometrium but not in MS endometrium. Interestingly, both fetal sex and fetal genome interact to influence endometrial gene expression.ConclusionsThese data provide evidence for some sexual dimorphism in the pregnant endometrium and for the contribution of the fetal genome to feto-maternal interactions at the end of gestation. They suggest that the paternal genome may contribute significantly to piglet survival, especially in crossbreeding production systems.

Regulation of m6Am RNA modification and its implications in human diseases.

N 6,2'-O-dimethyladenosine (m6Am) is a prevalent modification frequently found at the 5' cap-adjacent adenosine of mRNAs and snRNAs and the internal adenosine of snRNAs. This dynamic and reversible modification is under the regulation of methyltransferases PCIF1 and METTL4, along with the demethylase FTO. m6Am RNA modification plays a crucial role in the regulation of pre-mRNA splicing, mRNA stability, and translation, thereby influencing gene expression. In recent years, there has been growing interest in exploring the functions of m6Am and its relevance to human diseases. In this review, we provide a comprehensive overview of the current knowledge concerning m6Am, with a focus on m6Am-modifying enzymes, sequencing approaches for its detection, and its impacts on pre-mRNA splicing, mRNA stability, and translation regulation. Furthermore, we highlight the roles of m6Am in the context of obesity, viral infections, and cancers, unravelling its underlying regulatory mechanisms.

The Potential of Cold Plasma-Based Seed Treatments in Legume–Rhizobia Symbiotic Nitrogen Fixation: A Review

The use of cold plasma (CP) seed treatment is an emerging agricultural technology that exhibits the potential to enhance nodulation and symbiotic nitrogen fixation (SNF) in legumes. CP is composed of a diverse mixture of excited atoms, molecules, ions, and radicals that have the potential to affect the physical properties of the seed and influence gene expressions that could have a lasting impact on the nodulation, SNF, growth, and yield of legumes. The direct participation of the CP in the nodulation process and its correlation with the escalation of nodules and SNF is still not fully understood. This review discussed four areas in the nodulation and SNF process that can directly or indirectly affect CP seed treatments: root–rhizobia signal exchange pathways, root/shoot growth and development, phytohormone production, and the nitrogen fixation process. We also discuss the potential challenges and future research requirements associated with plasma technology to enhance SNF in legumes.

Functional Selectivity of Cannabinoid Type 1 G Protein-Coupled Receptor Agonists in Transactivating Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition Metastatic Phenotype.

Understanding the role of biased G protein-coupled receptor (GPCR) agonism in receptor signaling may provide novel insights into the opposing effects mediated by cannabinoids, particularly in cancer and cancer metastasis. GPCRs can have more than one active state, a phenomenon called either 'biased agonism', 'functional selectivity', or 'ligand-directed signaling'. However, there are increasing arrays of cannabinoid allosteric ligands with different degrees of modulation, called 'biased modulation', that can vary dramatically in a probe- and pathway-specific manner, not from simple differences in orthosteric ligand efficacy or stimulus-response coupling. Here, emerging evidence proposes the involvement of CB1 GPCRs in a novel biased GPCR signaling paradigm involving the crosstalk between neuraminidase-1 (Neu-1) and matrix metalloproteinase-9 (MMP-9) in the activation of glycosylated receptors through the modification of the receptor glycosylation state. The study findings highlighted the role of CB1 agonists AM-404, Aravnil, and Olvanil in significantly inducing Neu-1 sialidase activity in a dose-dependent fashion in RAW-Blue, PANC-1, and SW-620 cells. This approach was further substantiated by findings that the neuromedin B receptor inhibitor, BIM-23127, MMP-9 inhibitor, MMP9i, and Neu-1 inhibitor, oseltamivir phosphate, could specifically block CB1 agonist-induced Neu-1 sialidase activity. Additionally, we found that CB1 receptors exist in a multimeric receptor complex with Neu-1 in naïve, unstimulated RAW-Blue, PANC-1, and SW-620 cells. This complex implies a molecular link that regulates the interaction and signaling mechanism among these molecules present on the cell surface. Moreover, the study results demonstrate that CB1 agonists induce NFκB-dependent secretory alkaline phosphatase (SEAP) activity in influencing the expression of epithelial-mesenchymal markers, E-cadherin, and vimentin in SW-620 cells, albeit the impact on E-cadherin expression is less pronounced compared to vimentin. In essence, this innovative research begins to elucidate an entirely new molecular mechanism involving a GPCR signaling paradigm in which cannabinoids, as epigenetic stimuli, may traverse to influence gene expression and contribute to cancer and cancer metastasis.

Aphid gene expression following polerovirus acquisition is host species dependent.

Upon acquisition of persistent circulative viruses such as poleroviruses, the virus particles transcytose through membrane barriers of aphids at the midgut and salivary glands via hemolymph. Such intricate interactions can influence aphid behavior and fitness and induce associated gene expression in viruliferous aphids. Differential gene expression can be evaluated by omics approaches such as transcriptomics. Previously conducted aphid transcriptome studies used only one host species as the source of virus inoculum. Viruses typically have alternate hosts. Hence, it is not clear how alternate hosts infected with the same virus isolate alter gene expression in viruliferous vectors. To address the question, this study conducted a transcriptome analysis of viruliferous aphids that acquired the virus from different host species. A polerovirus, cotton leafroll dwarf virus (CLRDV), which induced gene expression in the cotton aphid, Aphis gossypii Glover, was assessed using four alternate hosts, viz., cotton, hibiscus, okra, and prickly sida. Among a total of 2,942 differentially expressed genes (DEGs), 750, 310, 1,193, and 689 genes were identified in A. gossypii that acquired CLRDV from infected cotton, hibiscus, okra, and prickly sida, respectively, compared with non-viruliferous aphids that developed on non-infected hosts. A higher proportion of aphid genes were overexpressed than underexpressed following CLRDV acquisition from cotton, hibiscus, and prickly sida. In contrast, more aphid genes were underexpressed than overexpressed following CLRDV acquisition from okra plants. Only four common DEGs (heat shock protein, juvenile hormone acid O-methyltransferase, and two unannotated genes) were identified among viruliferous aphids from four alternate hosts. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that the acquisition of CLRDV induced DEGs in aphids associated with virus infection, signal transduction, immune systems, and fitness. However, these induced changes were not consistent across four alternate hosts. These data indicate that alternate hosts could differentially influence gene expression in aphids and presumably aphid behavior and fitness despite being infected with the same virus isolate.

Unfurling the functional association between long intergenic noncoding RNAs (lincRNAs) and HPV16-related cervical cancer pathogenesis through weighted gene co-expression network analysis of differentially expressed lincRNAs and coding genes.

Long intergenic noncoding RNAs (lincRNAs) do not overlap annotated coding genes and are located in intergenic regions, as opposed to antisense and sense-intronic lncRNAs, located in genic regions. LincRNAs influence gene expression profiles and are thereby key to disease pathogenesis. In this study, we assessed the association between lincRNAs and HPV16-positive cervical cancer (CaCx) pathogenesis using weighted gene co-expression network analysis (WGCNA) with coding genes, comparing differentially expressed lincRNA and coding genes (DElincGs and DEcGs, respectively) in HPV16-positive patients with CaCx (n = 44) with those in HPV-negative healthy individuals (n = 34). Our analysis revealed five DElincG modules, co-expressing and correlating with DEcGs. We validated a substantial number of such module-specific correlations in the HPV16-positive cancer TCGA-CESC dataset. Four such modules, displayed significant correlations with patient traits, such as HPV16 physical status, lymph node involvement, and overall survival (OS), highlighting a collaborative effect of all genes within specific modules on traits. Using the DAVID bioinformatics knowledgebase, we identified the underlying biological processes associated with these modules as cancer development and progression-associated pathways. Next, we identified the top 10 DElincGs with the highest connectivity within each functional module. Focusing on the prognostic module hub genes, downregulated CTD-2619J13.13 expression was associated with poor patient OS. This lincRNA gene interacted with 25 coding genes of its module and was associated with such biological processes as keratinization loss and keratinocyte differentiation, reflecting severe disease phenotypes. This study has translational relevance in fighting various cancers with high mortality rates in underdeveloped countries.

Developments and future prospects of personalized medicine in head and neck squamous cell carcinoma diagnoses and treatments.

Precision healthcare has entered a new era because of the developments in personalized medicine, especially in the diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC). This paper explores the dynamic landscape of personalized medicine as applied to HNSCC, encompassing both current developments and future prospects. The integration of personalized medicine strategies into HNSCC diagnosis is driven by the utilization of genetic data and biomarkers. Epigenetic biomarkers, which reflect modifications to DNA that can influence gene expression, have emerged as valuable indicators for early detection and risk assessment. Treatment approaches within the personalized medicine framework are equally promising. Immunotherapy, gene silencing, and editing techniques, including RNA interference and CRISPR/Cas9, offer innovative means to modulate gene expression and correct genetic aberrations driving HNSCC. The integration of stem cell research with personalized medicine presents opportunities for tailored regenerative approaches. The synergy between personalized medicine and technological advancements is exemplified by artificial intelligence (AI) and machine learning (ML) applications. These tools empower clinicians to analyze vast datasets, predict patient responses, and optimize treatment strategies with unprecedented accuracy. The developments and prospects of personalized medicine in HNSCC diagnosis and treatment offer a transformative approach to managing this complex malignancy. By harnessing genetic insights, biomarkers, immunotherapy, gene editing, stem cell therapies, and advanced technologies like AI and ML, personalized medicine holds the key to enhancing patient outcomes and ushering in a new era of precision oncology.

Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.

Glaucoma, a complex and multifactorial neurodegenerative disorder, is a leading cause of irreversible blindness worldwide. Despite significant advancements in our understanding of its pathogenesis and management, early diagnosis and effective treatment of glaucoma remain major clinical challenges. Epigenetic modifications, encompassing deoxyribonucleic acid (DNA) methylation, histone modifications, and non-coding RNAs, have emerged as critical regulators of gene expression and cellular processes. The aim of this comprehensive review focuses on the emerging field of epigenetics and its role in understanding the complex genetic and molecular mechanisms underlying glaucoma. The review will provide an overview of the pathophysiology of glaucoma, emphasizing the intricacies of intraocular pressure regulation, retinal ganglion cell dysfunction, and optic nerve damage. It explores how epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression, and how these mechanisms are implicated in glaucomatous neurodegeneration and contribute to glaucoma pathogenesis. The manuscript discusses evidence from both animal models and human studies, providing insights into the epigenetic alterations associated with glaucoma onset and progression. Additionally, it discusses the potential of using epigenetic modifications as diagnostic biomarkers and therapeutic targets for more personalized and targeted glaucoma treatment.

Starvation differentially affects gene expression, immunity and pathogen susceptibility across symbiotic states in a model cnidarian.

Mutualistic symbioses between cnidarians and photosynthetic algae are modulated by complex interactions between host immunity and environmental conditions. Here, we investigate how symbiosis interacts with food limitation to influence gene expression and stress response programming in the sea anemone Exaiptasia pallida (Aiptasia). Transcriptomic responses to starvation were similar between symbiotic and aposymbiotic Aiptasia; however, aposymbiotic anemone responses were stronger. Starved Aiptasia of both symbiotic states exhibited increased protein levels of immune-related transcription factor NF-κB, its associated gene pathways, and putative target genes. However, this starvation-induced increase in NF-κB correlated with increased immunity only in symbiotic anemones. Furthermore, starvation had opposite effects on Aiptasia susceptibility to pathogen and oxidative stress challenges, suggesting distinct energetic priorities under food scarce conditions. Finally, when we compared starvation responses in Aiptasia to those of a facultative coral and non-symbiotic anemone, 'defence' responses were similarly regulated in Aiptasia and the facultative coral, but not in the non-symbiotic anemone. This pattern suggests that capacity for symbiosis influences immune responses in cnidarians. In summary, expression of certain immune pathways-including NF-κB-does not necessarily predict susceptibility to pathogens, highlighting the complexities of cnidarian immunity and the influence of symbiosis under varying energetic demands.

MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer

Cervical cancer, a leading global cause of female mortality, exhibits diverse molecular aberrations influencing gene expression and signaling pathways. Epigenetic factors, including histone deacetylases (HDACs) such as HDAC8 and HDAC6, along with microRNAs (miRNAs), play pivotal roles in cervical cancer progression. Recent investigations have unveiled miRNAs as potential regulators of HDACs, offering a promising therapeutic avenue. This study employed in-silico miRNA prediction, qRT-PCR co-expression studies, and Dual-Luciferase reporter assays to identify miRNAs governing HDAC8 and HDAC6 in HeLa, cervical cancer cells. Results pinpointed miR-497–3p and miR-324–3p as novel negative regulators of HDAC8 and HDAC6, respectively. Functional assays demonstrated that miR-497–3p overexpression in HeLa cells suppressed HDAC8, leading to increased acetylation of downstream targets p53 and α-tubulin. Similarly, miR-324–3p overexpression inhibited HDAC6 mRNA and protein expression, enhancing acetylation of Hsp90 and α-tubulin. Notably, inhibiting HDAC8 via miRNA overexpression correlated with reduced cell viability, diminished epithelial-to-mesenchymal transition (EMT), and increased microtubule bundle formation in HeLa cells. In conclusion, miR-497–3p and miR-324–3p emerge as novel negative regulators of HDAC8 and HDAC6, respectively, with potential therapeutic implications. Elevated expression of these miRNAs in cervical cancer cells holds promise for inhibiting metastasis, offering a targeted approach for intervention in cervical malignancy.

Epigenetic modifications in solid tumor metastasis in people of African ancestry.

This review focuses on the critical role of epigenetic modifications in solid tumor metastasis, particularly in people of African ancestry. Epigenetic alterations, such as DNA methylation, histone modifications, alterations in non-coding RNAs, and mRNA methylation, significantly influence gene expression, contributing to cancer development and progression. Despite the primary focus on populations of European, American, and Asian descent in most cancer research, this work emphasizes the importance of studying the unique genetic and epigenetic landscapes of African populations for a more inclusive approach in understanding and treating cancer. Insights from this review have the potential to pave the way for the development of effective, tailored treatments, and provide a richer resource for understanding cancer progression and metastasis. Specific focus was placed on the role of DNA methylation, histone modifications, non-coding RNAs, and mRNA methylation in solid tumor metastasis, including how these modifications contribute to the regulation of tumor suppressor genes and oncogenes, influence cellular pathways and signaling, and interact with the immune system. Moreover, this review elaborates on the development of epigenetic-targeted therapeutic strategies and the current advances in this field, highlighting the promising applications of these therapies in improving outcomes for African ancestry populations disproportionately affected by certain types of cancer. Nevertheless, this work acknowledges the challenges that lie ahead, particularly the under-representation of African populations in cancer genomic and epigenomic studies and the technical complications associated with detecting subtle epigenetic modifications. Emphasis is placed on the necessity for more inclusive research practices, the development of more robust and sensitive methods for detecting and interpreting epigenetic changes, and the understanding of the interplay between genetic and epigenetic variations. The review concludes with an optimistic outlook on the future of epigenetic research in People of African ancestry, urging the concerted efforts of researchers, clinicians, funding agencies, and policymakers to extend the benefits of this research to all populations.

Snowprint: a predictive tool for genetic biosensor discovery

Bioengineers increasingly rely on ligand-inducible transcription regulators for chemical-responsive control of gene expression, yet the number of regulators available is limited. Novel regulators can be mined from genomes, but an inadequate understanding of their DNA specificity complicates genetic design. Here we present Snowprint, a simple yet powerful bioinformatic tool for predicting regulator:operator interactions. Benchmarking results demonstrate that Snowprint predictions are significantly similar for >45% of experimentally validated regulator:operator pairs from organisms across nine phyla and for regulators that span five distinct structural families. We then use Snowprint to design promoters for 33 previously uncharacterized regulators sourced from diverse phylogenies, of which 28 are shown to influence gene expression and 24 produce a >20-fold dynamic range. A panel of the newly repurposed regulators are then screened for response to biomanufacturing-relevant compounds, yielding new sensors for a polyketide (olivetolic acid), terpene (geraniol), steroid (ursodiol), and alkaloid (tetrahydropapaverine) with induction ratios up to 10.7-fold. Snowprint represents a unique, protein-agnostic tool that greatly facilitates the discovery of ligand-inducible transcriptional regulators for bioengineering applications. A web-accessible version of Snowprint is available at https://snowprint.groov.bio.