Wilms' tumor (WT) is the most prevalent renal cancer in children. Numerous studies have shown that vir-like n6-methyladenosine (m6A) methyltransferase-associated protein (VIRMA), a necessary component and the largest methyltransferase, contributes to the advancement of multiple cancers. However, its function has not been characterized in WT. Hence, we examined the potential role of VIRMA in WT by analyzing its effect on the m6A modification of stearoyl-CoA desaturase (SCD). We utilized bioinformatics to narrow 12 differentially expressed (DE) genes in WT to a single gene. The expressions of SCD and VIRMA were analyzed via quantitative real-time PCR and western blotting. The influence of SCD on the malignancy attributes of WT cells and adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling was assessed through Cell counting Kit-8, Ethynyl-2'-deoxyuridine, transwell, and western blotting assays. The specific interactions between SCD and VIRMA were confirmed through methylated RNA immunoprecipitation, western blotting, and RNA stability assays, followed by rescue experiments to show underlying mechanisms. The SCD expression was found to be elevated in WT samples. Furthermore, its silencing mitigated the malignant characteristics of WT cells while increasing the protein levels of key AMPK signaling molecules. Moreover, VIRMA was also upregulated in WT samples and demonstrated a positive association with SCD expression. The relative enrichment of SCD m6A, its protein, and its mRNA stability were enhanced in VIRMA-overexpressed WT cells. Mechanically, VIRMA overexpression accelerated the malignant phenotypes of WT cells by interacting with SCD. Overall, the results demonstrate that VIRMA-mediated m6A methylation of SCD promotes WT progression by modulating the AMPK pathway.

This study investigated the impact of lidocaine-induced neurotoxicity on microRNA (miRNA) expression in the spinal cord of rats. Sprague-Dawley rats underwent intrathecal catheterization and were randomly assigned to receive either 10% lidocaine or normal saline for three consecutive days. Post-treatment, the paw withdrawal threshold significantly increased, accompanied by notable histopathological changes. Additionally, 470 miRNAs exhibited altered expression following lidocaine treatment, with , , and showing significant changes. Gene Ontology analysis identified cellular metabolic processes as the most significantly enriched functions. Kyoto encyclopedia of genes and genomes pathway analysis revealed that the enriched signaling pathways are associated with neural injury and neuroprotection, and are involved in regulating cellular metabolism. The Mitogen-Activated Protein Kinase (MAPK) signaling pathway was notably enriched, with and identified as target genes of . Following lidocaine treatment, there was an observed increase in the expression of MAP3K10 and MAP3K14 at both the mRNA and protein levels. These results indicate that , , and might be significantly involved in lidocaine-induced neurotoxicity by influencing cellular metabolism. Furthermore, /MAPK shows potential therapeutic value for treating lidocaine-induced neurotoxicity.

According to the World Health Organization, infections affect approximately 25% of the world's population. There is mounting evidence linking autophagy and immunological dysregulation to tuberculosis (TB). As a result, this research set out to discover TB-related autophagy-related biomarkers and prospective treatment targets. We used five autophagy databases to get genes linked to autophagy and Gene Expression Omnibus databases to get genes connected to TB. Then, functional modules associated with autophagy were obtained by analyzing them using weighted gene co-expression network analysis. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to examine the autophagy-related genes (ATGs) of important modules. Limma was used to identify differentially expressed ATGs (DE-ATGs), and the external datasets were used to further confirm their identification. We used DE-ATGs and a protein-protein interaction network to search the hub genes. CIBERSORT was used to estimate the kinds and amounts of immune cells. After that, we built a drug-gene interaction network and a network that included messenger RNA, small RNA, and DNA. At last, the differential expression of hub ATGs was confirmed by RT-qPCR, immunohistochemistry, and western blotting. The diagnostic usefulness of hub ATGs was evaluated using receiver operating characteristic curve analysis. Including 508 ATGs, four of the nine modules strongly linked with TB were deemed essential. Interleukin 1B (), , and signal transducer and activator of transcription 1 () were identified by intersection out of 22 DE-ATGs discovered by differential expression analysis. Research into immune cell infiltration found that patients with TB had an increased proportion of plasma cells, CD8 T cells, and M0 macrophages. A competitive endogenous RNA network utilized 10 long non-coding RNAs and 2 miRNAs. Then, the -targeted drug Cankinumad was assessed using this network. During bioinformatics analysis, three hub genes were validated in mouse and macrophage infection models. We found that , , and are important biomarkers for TB. As a result, these crucial hub genes may hold promise as TB treatment targets.

Liquiritin, a key component extracted from , exhibits a variety of physiological effects. This study investigates the role of liquiritin in the progression of breast cancer. This investigation conducted experiments using two breast cancer cell lines treated with varying concentrations of liquiritin, further validating our findings . Bioinformatics analysis was used to identify the pathways potentially regulated by liquiritin in breast cancer. The results indicated that the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase 8 (MAPK8) are potential downstream factors regulated by liquiritin in breast cancer. Our findings demonstrated that liquiritin significantly suppressed cell proliferation and induced cell cycle arrest in a dose-dependent manner. In addition, liquiritin triggered apoptosis by inhibiting the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Liquiritin also reduced mitochondrial membrane potential, leading to mitochondrial dysfunction and promoting excessive reactive oxygen species (ROS) production by suppressing the EGFR/MAPK8 signaling pathway. Furthermore, liquiritin treatment resulted in a notable decrease in tumor size in breast cancer models through inhibiting cell proliferation and promoting apoptosis. In conclusion, liquiritin serves as an effective tumor suppressor, suppressing the proliferation and cell cycle progression of breast cancer cells, while inducing apoptosis by regulating mitochondrial function and ROS generation via the EGFR/MAPK8 signaling pathway.

Breast cancer (BC) is a significant contributor to cancer-related deaths in women, and it has complex connections with obesity and aging. This review explores the interaction between obesity and aging in relation to the development and progression of BC, focusing on the controlling role of microRNAs (miRNAs). Obesity, characterized by excess adipose tissue, contributes to a proinflammatory environment and metabolic dysregulation, which are important in tumor development. Aging, associated with cellular senescence and systemic changes, further exacerbates these conditions. miRNAs, small noncoding RNAs that regulate gene expression, play key roles in these processes, impacting pathways involved in cell proliferation, apoptosis, and cancer metastasis, either as tumor suppressors or oncogenes. Importantly, specific miRNAs are implicated in mediating the impact of obesity and aging on BC. Exploring the regulatory networks controlled by miRNAs provides valuable information on new targets for therapy and predictive markers, demonstrating the potential for using miRNA-based interventions to treat BC in obese and elderly individuals. This review emphasizes the importance of integrated research strategies to understand the complex connections between obesity, aging, and miRNA regulation in BC.

The number of cases of papillary thyroid cancer (PTC) has gone up significantly in recent years, with high recurrence. Numerous reports have highlighted the participation of circular RNAs (circRNAs) in regulating the advancement of cancers, including PTC. Furthermore, recent studies suggest that N6-methyladenosine (m6A) modified circRNAs play pivotal roles in cancer progression. Hence, we studied the potential role of a novel circRNA, hsa_circ_0136959, and its regulatory mechanism on m6A modification by methyltransferase-like 3 (METTL3) in the tumor characteristics of PTC. The expressions of hsa_circ_0136959 and were evaluated in PTC samples and cell lines via quantitative real-time polymerase chain reaction. The effect of hsa_circ_0136959 on the malignant properties of PTC was analyzed by performing Cell Counting Kit-8, colony formation, and transwell assays. In addition, its effects on the levels of markers related to ferroptosis (reactive oxygen species, Fe, and iron) in PTC cells were also assessed. Bioinformatics analysis was done to determine the hsa_circ_0136959 expression and m6A modification sites on it in PTC. The m6A level of hsa_circ_0136959 was analyzed through methylated (m6A) RNA immunoprecipitation. The hsa_circ_0136959 was observed to be downregulated in both PTC samples and cells. experiments showed that its overexpression impeded the malignant properties of PTC cells. Moreover, hsa_circ_0136959 overexpression increased the levels of ferroptosis-related markers in PTC cells. We also found that was notably reduced in PTC samples and was positively correlated with hsa_circ_0136959. Mechanistically, METTL3 enhanced hsa_circ_0136959 expression through m6A modification. Our results demonstrate that METTL3-mediated m6A modification elevated hsa_circ_0136959 expression and subsequently restricted the tumor characteristics of PTC by accelerating ferroptosis.

Liver fibrosis (LF) is a clinical disorder characterized by inflammation and excessive accumulation of extracellular matrix (ECM). This study investigates the effects of the antifibrotic compound pirfenidone (PFD) on improving LF through histological changes and modulation of eukaryotic translation initiation factor 6 (eIF6), P311, and transforming growth factor beta (TGF-β) in rats with bile duct ligation (BDL)-induced LF. Rats received daily doses of PFD (200 and 500 mg/kg) for 4 weeks. The study encompassed biochemical, pathological, and immunohistochemical (IHC) analyses. mRNA levels of eIF6, P311, TGF-β, ECM deposition, hepatic stellate cell (HSC) activation, and inflammatory mediator genes were measured by RT-qPCR. Protein levels of eIF6, P311, and TGF-β were detected by western blotting. Compared with the BDL group, PFD dose-dependently reduced hydroxyproline content, liver index, biochemical parameters, fibrosis score, and fibrosis area. PFD also modulated BDL-induced hepatic inflammation, ECM accumulation, and HSC activation. IHC staining of Ki-67 and hepatocyte paraffin-1 revealed that PFD enhanced liver regeneration. The research confirmed that PFD gradually downregulated elevated eIF6, P311, and TGF-β levels in BDL-induced LF. These findings suggest that PFD could be a potential treatment for LF, as it may help attenuate fibrosis and enhance liver regeneration, possibly through the modulation of these specific markers.

Hereditary spinocerebellar ataxia (SCA) is a group of genetic neurodegenerative disorders caused by a variety of gene variants. At least 44 types of SCAs have been identified to date, and more than 35 genes and hundreds of variants have been reported that are associated with SCAs. We have investigated a Pakistani consanguineous six-generation family with SCA by using whole-exome sequencing analysis. We identified a reported SCA-associated variant, c.C2687G (p.P896R) in , in only a subgroup of the family, while a c.C262T (p.P88S) variant in serves as a candidate pathogenic variant in the other subgroup as a possible novel cause of SCA. Our study showed that intra-familial heterogeneity may exist in SCA families and presented a candidate new causative gene for SCA.

Exosome-delivered circular RNAs (circRNAs) are recognized as a key mechanism that regulates osteosarcoma (OS) progression. The purpose of this study is to discover the role of a novel circRNA hsa_circ_0000116 from exosomes in OS progression. Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to identify the exosomes isolated from two OS cell lines (HOS and MG-63). After coculturing exosomes with OS cells and transfecting hsa_circ_0000116 knockdown vector into OS cells, cell function experiments, including cell counting kit-8, wound healing, and Transwell experiments, were performed to assess the change of OS cell malignant phenotype. In addition, the levels of PI3K/Akt/mTOR and p38/MAPK pathways-associated proteins were measured using western blotting. Exosomes with around 100 nm in diameter were successfully isolated from HOS and MG-63 cells, and promote OS cells to proliferate, migrate, and invade. hsa_circ_0000116 was upregulated in OS-derived exosomes, and silencing hsa_circ_0000116 declined the exosome-induced OS cell malignancy. In addition, inhibiting hsa_circ_0000116 effectively inhibited exosome-mediated activation of PI3K/Akt/mTOR and p38/MAPK pathways. In conclusion, exosomal hsa_circ_0000116 can facilitate OS cell malignancy by inducing the activation of PI3K/Akt/mTOR and p38/MAPK pathways. The findings of this study may identify novel molecular mechanisms driving OS progression and provide novel therapeutic targets for OS.

Liver fibrosis, one of the main histological determinants of various chronic liver diseases, currently lacks effective treatment. Hepatic stellate cells (HSCs) are pivotal in the production of extracellular matrix and amplify the fibrogenic response. Inhibiting the activation of HSCs or promoting the senescence of activated HSCs is crucial for the regression of liver fibrosis. The ATPase p97, also known as valosin-containing protein (VCP), is a central component of the ubiquitin-proteasome system, and it regulates numerous cellular processes by influencing protein homeostasis. In this study, we observed an upregulation of p97 expression around regions exhibiting fibrosis in a diet- and chemical-induced nonalcoholic steatohepatitis and fibrosis murine model. Intervention with the p97 antagonist CB-5083 or the knockdown of p97 reduced the expression of alpha-smooth muscle actin and collagen-I in both mouse or human HSCs. The administration of CB-5083 induced HSC senescence and resulted in the upregulation of senescence markers, including p21, p53, GPX4, and senescence-associated β-galactosidase. Furthermore, CB-5083 treatment also inhibited the expression of Yes-associated protein (YAP), which is also a senescence-related regulatory protein and has a profibrotic function. We used CB-5083 to treat fibrotic mice and found that the activation of HSCs was inhibited, and the liver fibrosis was attenuated. In addition, experiments confirmed that CB-5083 facilitated HSC senescence and reduced YAP expression. These findings underscore the potential of pharmacological targeting p97/VCP to induce HSC senescence and alleviate liver fibrosis.

The pleural cavity is gaining recognition as an important player in lung infections. Our recent research revealed that pleural macrophages (PMs) migrate from the pleural cavity into the lung during influenza virus infection, contributing to improved disease outcomes. This summary highlights key findings on the role of PMs in influencing viral lung infection outcomes and explores the potential directions for advancing this emerging field of study.

The early and precise diagnosis of asthma significantly impacts the long-term health outcomes of pediatric patients. The sensitivity and specificity of current biomarkers, however, are frequently limited. Our study aimed to evaluate the clinical significance of nuclear factor of activated T cells, cytoplasmic 3 (NFATc3), in pediatric bronchial asthma, focusing on its diagnostic and prognostic value for disease severity and recurrence. This observational, prospective case-control study involved 200 pediatric patients with bronchial asthma and 200 age- and sex-matched healthy controls, from January 2020 to January 2023. Follow-up varied from 1 to 3 years. We measured levels of NFATc3 and inflammatory cytokines interleukin-1β (IL-1β), IL-6, and TNF-α via enzyme-linked immunosorbent assay. NFATc3 and IL-1β levels at enrollment were markedly higher in patients with acute exacerbations and those classified as severe, compared with their less severe counterparts. Throughout the study, NFATc3, IL-1β, and IL-6 levels significantly increased in severe or acutely exacerbating cases. The diagnostic value of NFATc3 was assessed through receiver operating characteristic curve analysis, which showed its potential in diagnosing bronchial asthma and identifying severe cases. Spearman's analysis confirmed positive associations between peak NFATc3 and cytokine levels. Importantly, disease type, NFATc3 values at enrollment, as well as peak IL-6 levels were identified as independent risk factors for severe bronchial asthma. Elevated NFATc3 is linked with the severity of pediatric bronchial asthma and serves as a potential biomarker for diagnosis and severity prediction, emphasizing its role in guiding treatment strategies.

Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most common subtype. The current standard of care for NSCLC has limited efficacy, highlighting the necessity for innovative treatment options. Lidocaine, traditionally recognized as a local anesthetic, has emerged as a compound with potential antitumor and anti-inflammatory capabilities. This study was designed to explore the impact of lidocaine on NSCLC cell proliferation and inflammation, particularly focusing on the Toll-like receptor 9 (TLR)-9/MyD88/NF-κB signaling pathway. A nude mice model of NSCLC was employed, with animals receiving lidocaine at different concentrations. experiments on A549 cells involved exposure to lidocaine, followed by assessment of cell viability, cytokine expression, and TLR-9 levels using the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, enzyme-linked immunosorbent assay, and Quantitative Real-time polymerase chain reaction (qPCR). Protein levels were evaluated via Western blot analysis. Additionally, A549 cells were transfected with a TLR-9-overexpressing lentivirus to dissect the role of TLR-9 in lidocaine's mechanism of action. Treatment with lidocaine led to a significant reduction in tumor dimensions and a decrease in inflammatory marker expression in the NSCLC mouse model. In cellular assays, lidocaine effectively suppressed A549 cell proliferation and the expression of inflammatory cytokines. The overexpression of TLR-9 partially negated the suppressive effects of lidocaine, underscoring the significance of the TLR-9/MyD88/NF-κB pathway in mediating lidocaine's effects. Lidocaine's inhibitory effects on NSCLC cell proliferation and its anti-inflammatory mechanisms are mediated through the TLR-9/MyD88/NF-κB pathway. The study's results offer promising insights into the therapeutic potential of lidocaine in NSCLC and pave the way for future investigations into its application in cancer therapy.

High-throughput DNA sequencing has accelerated the discovery of disease-causing genetic variants, yet only in 10-40% of cases yield a genetic diagnosis. Increased implementation of genome sequencing has enabled a deeper exploration of the noncoding genome and recognition of noncoding variants as major contributors to disease. In a recent study, we identified a deep intronic variant in the AutoImmune REgulator () gene (c.1504-818 G>A) as the cause of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a life-threatening monogenic autoimmune disorder most often caused by biallelic defects. This deep intronic variant disrupts normal splicing , causing pseudoexon inclusion and altered protein function. By developing an antisense oligonucleotide (ASO) targeting the pseudoexon sequence, we restored normal transcript , thereby revealing a potential genotype-specific candidate treatment. Our study illustrates key aspects of intronic variant detection, validation, and candidate ASO development. Herein, we briefly highlight the growing potential of ASO-based therapies for deep intronic variants, addressing the unmet need of personalized, genotype-specific therapies in diseases lacking curative options.

Hepatic ischemia-reperfusion (I/R) injury (HIRI) is recognized as a local aseptic inflammatory response driven by innate immunity and is considered a leading cause of early organ dysfunction and failure following liver transplantation. Etomidate (Eto), an anesthetic drug known for its ability to inhibit inflammatory response and apoptosis, was the focus of our investigation. In this study, we conducted hepatic I/R surgery on C57 mice, analyzing liver damage through histopathology. Additionally, primary hepatocytes isolated from mice were cultured and subjected to hypoxia/reoxygenation (H/R) insult , with cell activity assessed using the CCK8 assay and immunofluorescence staining employed to analyze liver inflammatory cell infiltration and apoptosis. Results showed that Eto effectively inhibited liver injury, inflammatory response, and apoptosis induced by HIRI surgery, with the greatest effect observed at an Eto concentration of 10 mg/kg. Furthermore, Eto also showed the ability to inhibit H/R-induced cell damage, inflammatory activation, and apoptosis in primary hepatocytes. Further mechanistic studies revealed that Eto could promote the activation of the Nrf2-HO-1 signaling pathway, and the protective effect of Eto on HIRI was nullified when the Nrf2 inhibitor ML385 was utilized. This study highlights the potential of Eto to protect against HIRI by promoting the Nrf2-HO-1 signaling axis.

Systemic lupus erythematosus is a chronic autoimmune disease that has been associated with human leukocyte antigen G (HLA-G) in previous studies on immunological diseases. This study aimed to investigate the association between three HLA-G gene polymorphisms (rs1632947, rs1233334, and rs371194629) and their impact on HLA-G mRNA expression and soluble HLA-G levels in serum. Genotyping was performed using TaqMan probe PCR. RNA extraction, reverse transcription PCR, and real-time PCR assays were conducted to assess the expression of the HLA-G gene in tissue samples. Soluble HLA-G was measured using enzyme-linked immunosorbent assay in serum. Results show a significant difference in the frequency of the G allele for two 5'-untranslated region (UTR) polymorphisms of the HLA-G gene (rs1632947 and rs1233334) located at positions -964 and -725, respectively, between lupus patients and controls, with -values of 0.009 and 0.040, respectively. In addition, the study identified the 14 bp insertion allele of the rs371194629 polymorphism located in the 3' UTR of the gene as a risk factor for lupus, with a -value of 0.001. Our results also indicate that lupus-related alleles may increase the risk of developing the disease by upregulating the expression of HLA-G and increasing soluble HLA-G levels in serum. The findings of the study suggest that the identified genetic variants may play a role in the development of lupus and could be useful in identifying individuals at risk for the disease. These results are important for advancing our understanding of the genetic basis of lupus and may have implications for the development of new treatments and diagnostic tools for the disease.

Long noncoding RNAs (lncRNAs) have emerged as critical regulators in the development of colorectal cancer (CRC). Previous studies indicate that lncRNA is highly expressed in CRC, but its role in modulating CRC via the signaling pathway remains unclear. In this study, we found that promotes the growth of the CRC cell line (HCT116) and drives epithelial-mesenchymal transition (EMT) through the signaling pathway. Our data showed that expression is significantly upregulated in HCT116, and elevated levels of are associated with poor prognosis in patients with CRC. In addition, the knockdown of markedly inhibited the proliferation of HCT116 by inducing cell cycle arrest. Knockdown of depletion also led to apoptosis in CRC cells by suppressing the signaling pathway and EMT, thereby reducing their viability, proliferation, migration, and invasion. In summary, this study confirmed that regulates the growth of junction HCT116 through signaling pathway and inhibiting EMT, providing new insights for the potential therapeutic strategies against CRC.

Hypertension is the leading risk for cardiovascular disease and worldwide mortality. Uncontrolled blood pressure worsens with age and its control is part of public health strategies especially for older adults. Telomere length (TL) has been associated with hypertension, with age and sex as relevant confounding factors, but it is not clear whether hypertension control in older adults impacts on TL and if this relationship is consistently age and sex dependent. TL was assessed in leukocytes of 369 hypertensive patients. Individuals were >60 years male (169) and female (200) and have been diagnosed and treated for hypertension for at least four years. TL was measured by RT-PCR using a commercial probe. Regression models were developed considering systolic and diastolic blood pressure control as dependent variables and age, sex, glucose, and lipid levels as confounding factors. TL showed a mean of 7.5 ± 5.1 Kb, and no difference between males and females was observed. We identified a significant association between systolic blood pressure control and TL ( value = 0.039) and a trend for diastolic blood pressure ( value = 0.061). These observations confirm and expand previous reports showing that hypertension control can have an impact on TL and consequently on other factors of healthy aging.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The discovery of new effective therapeutic drugs is always a priority. Magnesium lithospermate B (MLB), a native polyphenol acid, is the major component of the aqueous extracts from Danshen, a traditional Chinese medicine derived from the dry root and rhizome of . MLB has been reported to have antioxidant, anti-inflammatory, and ion channel-regulating activities in several diseases, including cardiovascular, renal, and neuronal diseases. However, the effect of MLB on cancer progression has not been reported. In this study, a series of cellular and molecular experiments were conducted on two CRC cell lines (HCT116 and SW480) to investigate the effects of. The results demonstrated that MLB exerted inhibitory effects on cell proliferation, migration, and invasion. The administration of 50 mg/kg MLB inhibited tumor growth in HCT116 cells in xenografted models. Importantly, we found that MLB treatment inhibited the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway, and activation of JAK2-STAT3 signaling with interleukin 6 or overexpression STAT3 significantly suppressed the inhibitory effect of MLB. These findings provide evidence that MLB could inhibit CRC cell progression and might serve as a potential therapeutic drug for the treatment of CRC.

Cervical cancer (CC) is the most common cancer in women. This study aims to explore the molecular mechanism of lactate secreted by CC cells modulating macrophage polarization in CC via histone lactylation. Normal cervical epithelium (NCE), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical squamous cell carcinoma (CESC) were collected to assess H3K18la level and macrophage infiltration. Macrophages were incubated with SiHa cell-derived conditioned medium to detect M1 and M2 markers. NCE, HSIL, and CESC samples were used for ChIP-seq of H3K18la. Histone lactylation-dirven was knocked down in macrophages. Compared to NCE, H3K18la level and M2 macrophage abundance were increased in LSIL, HSIL, and CESC. Lactate secreted by CC cells upregulated H3K18la and M2 markers but downregulated M1 markers in macrophages. ChIP-seq revealed that upregulated pathways in HSIL vs. NCE and CESC vs. HSIL were commonly enriched in lipid metabolism. Notably, lactate upregulated H3K18la-modified expression in macrophages, and knockdown reversed lactate induction to M2 macrophages. Collectively, lactate secreted by CC cells upregulates via histone lactylation, thereby promoting M2 macrophage polarization in CC. This study provides new insights into the role of histone lactylation in macrophage polarization in the malignant transformation of CC.

One of the main health issues in the modern world is cancer, with breast cancer (BC) as one of the most common types of malignancies. Different environmental and genetic risk factors are involved in the development of BC. One of the primary genes implicated in cancer development is the p53 gene, which is also known as the "gatekeeper" gene. p53 is involved in cancer development by interacting with numerous pathways and signaling factors, including microRNAs (miRNAs). miRNAs are small noncoding RNA molecules that regulate gene expression by binding to the 3' untranslated region of target mRNAs, resulting in their translational inhibition or degradation. If the p53 gene is mutated or degraded, it can contribute to the risk of BC by disrupting the expression of miRNAs. Similarly, the disruption of miRNAs causes the negative regulation of p53. Therefore, the p53/miRNA axis is a crucial pathway in the progression or prevention of BC, and understanding the regulation and function of this pathway may contribute to the development of new therapeutic strategies to help treat BC.