Gastric cancer remains one of the deadliest cancers globally due to delayed detection and limited treatment options, underscoring the critical need for innovative prognostic methods. Disulfidptosis, a recently discovered programmed cell death triggered by disulphide stress, presents a fresh avenue for therapeutic exploration. This research examines disulfidptosis-related long noncoding RNAs (DRLs) in gastric cancer, with the goal of leveraging these lncRNAs as potential markers to enhance patient outcomes and treatment approaches. Comprehensive genomic and clinical data from stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA). Employing least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic model was devised incorporating five key DRLs to forecast survival rates. The effectiveness of this model was validated using Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, and extensive functional enrichment studies. The importance of select lncRNAs and the expression variability of genes tied to disulfidptosis were validated via quantitative real-time PCR (qRT-PCR) and Western blot tests, establishing a solid foundation for their prognostic utility. Analyses of functional enrichment and tumour mutation burden highlighted the biological importance of these DRLs, connecting them to critical cancer pathways and immune responses. These discoveries broaden our comprehension of the molecular framework of gastric cancer and bolster the development of tailored treatment plans, highlighting the substantial role of DRLs in clinical prognosis and therapeutic intervention.

The present study aimed to explore the effects of key N6‑methyladenosine (m6A)‑related long non‑coding RNAs (lncRNAs) on the malignant behavior and macrophage polarization of gastric cancer cells, and their preliminary mechanisms. Gastric cancer‑related lncRNA datasets were downloaded from The Cancer Genome Atlas database, and m6A‑related differentially expressed lncRNAs (DElncRNAs) were analyzed. Subsequently, Cox regression and lasso regression analyses were used to screen the m6A‑related DElncRNAs associated with the prognosis of patients with gastric cancer. Additionally, reverse transcription‑quantitative polymerase chain reaction (qPCR) was employed to detect the expression levels of m6A‑related lncRNAs in normal gastric epithelial cells (GES‑1) and human gastric cancer cells (AGS and MKN‑45). In addition, the methylation levels of lncRNAs were measured using a methylated RNA immunoprecipitation qPCR assay kit, and the interaction between m6A‑related lncRNAs and m6A‑related proteins was observed by RNA pull‑down assay. Subsequently, m6A‑related lncRNAs and proteins were knocked down separately or simultaneously in gastric cancer cell lines. Bioinformatics analysis revealed that m6A‑related AC026691.1 was significantly associated with the prognosis of patients with gastric cancer and had a potential binding site for YT521‑B homology domain family member 2 (YTHDF2). The RNA pull‑down assay indicated that YTHDF2 not only had binding sites with AC026691.1 but could also markedly promote the degradation of m6A‑related AC026691.1. Furthermore, AC026691.1 was lowly expressed in gastric cancer cells, whereas YTHDF2 was highly expressed. Knockdown of YTHDF2 inhibited the proliferation, migration and epithelial‑mesenchymal transition of gastric cancer cells, and reduced M2 macrophage polarization. By contrast, knocking down AC026691.1 showed the opposite trend. Knockdown of YTHDF2 and AC026691.1 further confirmed the stable impact of YTHDF2 on AC026691.1. In conclusion, the degradation of AC026691.1 modified by YTHDF2‑mediated m6A may promote gastric cancer cell proliferation, migration, epithelial‑mesenchymal transition and M2 macrophage polarization.

Growing research indicates that long noncoding RNAs (lncRNAs) are pivotal in the development and advancement of hepatocellular carcinoma (HCC). Our research pinpointed LINC01547 as a notable lncRNA that was significantly downregulated in Hep3B cells treated with bufotalin, whereas it exhibited elevated expression levels in HCC tumor tissues. Further study found that silencing LINC01547 markedly suppressed proliferation, induced apoptosis, and inhibited migration and invasion in Hep3B and HepG2 cells. LINC01547 knockdown reduced ADAR1 expression, which led to apoptosis and suppressed metastasis via inhibition of the FAK signaling pathway. Additionally, silencing LINC01547 upregulated miR-146b-5p, which in turn decreased RAC1 levels, further promoting apoptosis and inhibiting metastasis in HCC cells. In vivo, a Hep3B tumor-bearing mouse model confirmed the antitumor effects of LINC01547 silencing. Our findings demonstrate that LINC01547 regulates HCC cell apoptosis and metastasis through the ADAR1/FAK and miR-146b-5p/RAC1 pathways, suggesting that LINC01547 may serve as a biomarker and potential therapeutic target for HCC.

Crown rot caused by Fusarium proliferatum is a severe postharvest disease of banana fruit. The N6-methyladenosine (m6A) modification is the most common type of RNA modification and regulates gene expression in eukaryotes. Here, we analyzed transcriptome-wide changes in m6A methylation to investigate post-transcriptional regulation mechanisms of growth and fumonisin biosynthesis of F. proliferatum after fluopyram (Flu) treatment. The results demonstrated that Flu treatment inhibited F. proliferatum growth but induced fumonisins (FB1 and FB2) production both in vitro and in vivo. A transcriptome-wide m6A methylation profile showed that m6A hypomethylation was induced by Flu and enriched in start codons and the 3' untranslated region. FpAlkbh8 and FpYthdc1 may contribute to the decrease in m6A modifications after Flu treatment. The expression levels of m6A-containing mRNAs were higher than those of non-m6A-containing mRNAs. Furthermore, Flu decreased the acetyl-CoA content and regulated glycolysis and tricarboxylic acid cycle through m6A modifications, diverting the acetyl-CoA flux into fumonisin biosynthesis. Importantly, Flu-mediated regulation of energy and reactive oxygen species metabolism, cell wall and membrane, and transcription factors was associated with m6A modifications. Collectively, this study provides potential novel targets for improving fungicide efficiency to control fungal disease and highlights the potential of environmental risks of fungicides.

Long non‑coding RNAs (lncRNAs) are key players in the regulation of gene expression by mediating epigenetic and epitranscriptomic modification. Dysregulation of lncRNAs is implicated in tumor initiation, progression and metastasis. lncRNAs modulate chromatin structure and gene transcription by recruiting epigenetic regulators, including DNA‑ or histone‑modifying enzymes. Additionally, lncRNAs mediate chromatin remodeling and enhancer‑promoter long‑range chromatin interactions to control oncogene expression by recruiting chromatin organization‑associated proteins, thereby promoting carcinogenesis. Furthermore, lncRNAs aberrantly induce oncogene expression by mediating epitranscriptomic modifications, including RNA methylation and RNA editing. The present study aimed to summarize the regulatory mechanisms of lncRNAs in cancer to unravel the complex interplay between lncRNAs and epigenetic/epitranscriptomic regulators in carcinogenesis. The present review aimed to provide a novel perspective on the epigenetic and epitranscriptomic roles of lncRNAs in carcinogenesis to facilitate identification of potential biomarkers and therapeutic targets for cancer diagnosis and treatment.

N6-methyladenosine (m6A) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within the tumor microenvironment (TME) and are essential for meeting the demands of cellular growth and maintaining tissue homeostasis, enabling cells to adapt to the specific conditions of the TME. An increasing number of research studies have focused on the role of m6A modifications in glucose, amino acid and lipid metabolism, revealing their capacity to induce aberrant changes in metabolite levels. These changes may in turn trigger oncogenic signaling pathways, leading to substantial alterations within the TME. Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids and cholesterol, exhibit pronounced deviations from normal levels. These deviations not only foster tumorigenesis, proliferation and angiogenesis but also give rise to an immunosuppressive TME, thereby facilitating immune evasion by the tumor.

The primary objective of this review is to comprehensively discuss the regulatory role of m6A modifications in the aforementioned metabolites and their potential impact on the development of an immunosuppressive TME through metabolic alterations.

This review aims to elaborate on the intricate networks governed by the m6A-metabolite-TME axis and underscores its pivotal role in tumor progression. Furthermore, we delve into the potential implications of the m6A-metabolite-TME axis for the development of novel and targeted therapeutic strategies in cancer research.

Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.

N6-methyladenosine (m6A) RNA methylation is crucially involved in the genesis and advancement of gastric cancer (GC) by controlling various pathobiological aspects including gene expression, signal transduction, metabolism, cell death, epithelial-mesenchymal transition, angiogenesis, and exosome function. Despite its importance, the exact mechanisms by which m6A modification influences GC biology remain inadequately explored. This review consolidates the latest advances in uncovering the mechanisms and diverse roles of m6A in GC and proposes new research and translational directions. Key regulators (writers, readers, and erasers) of m6A, such as METTL3/14/16 and WTAP, significantly affect cancer progression, anticancer immune response, and treatment outcomes. m6A modification also impacts immune cell infiltration and the tumor microenvironment, highlighting its potential as a diagnostic and prognostic marker. Interactions between m6A methylation and non-coding RNAs offer further novel insights into GC development and therapeutic targets. Targeting m6A regulators could enhance immunotherapy response, overcome treatment resistance, and improve oncological and clinical outcomes. Models based on m6A can precisely predict treatment response and prognosis in GC. Additional investigation is needed to fully understand the mechanisms of m6A methylation and its potential clinical applications and relevance (e.g., as precise markers for early detection, prediction of outcome, and response to therapy and as therapeutic targets) in GC. Future research should focus on in vivo studies, potential clinical trials, and the examination of m6A modification in other types of cancers.

To investigate the effects of hypoxia-related genes in stomach adenocarcinoma (STAD) and construct an excellent prognostic model.

RNA expression data and clinical details were retrieved from the TCGA and GEO database dataset. scRNA-seq analysis was conducted on primary gastric cancer samples from GSE183904. Cellular hypoxia status was predicted using the CHPF software. WGCNA and GO-BP/KEGG enrichment of module genes analyses were performed to identify gene modules associated with hypoxia and biological pathway enrichment. A prognostic model was developed employing the LassoCox algorithm. GES-1, AGS, BGC823, and MGC803 cell lines were obtained for qRT-PCR analysis to identify the expression of model genes.

Single-cell atlas within STAD delineated that most of neoplastic cells, fibroblasts, endothelial cells, and myeloid cells were hypoxic. Further analysis of neoplastic cell subpopulations identified four hypoxic subpopulations (H1-H4) and four non-hypoxic subpopulations (N1-N4), with H1 subpopulation had the highest degree of hypoxia. The prognostic model constructed by five H1-specific transcription factors EHF, EIF1AD, GLA, KEAPI, and MAGED2, was demonstrated efficacy in predicting overall survival (OS), with significantly worse OS in high-risk patients. qRT-PCR analysis determined the higher expression level of five H1-specific transcription factors in gastric cancer cell lines than that in normal gastric epithelial cell line.

Hypoxia exerts a profound influence on STAD due to the overexpression of hypoxic cellular subpopulations-specific transcription factors EHF, EIF1AD, GLA, KEAPI, and MAGED2. The novel prognostic model developed by these hypoxia-associated genes presents a novel approach to risk stratification, exhibiting an excellent prognostic value for STAD patients.

Gastric cancer (GC) is a highly aggressive malignancy associated with poor prognosis, particularly in its advanced stages. Neutrophil extracellular traps (NETs) have been implicated in cancer progression and immune therapy responses; however, the role of NETs-related long non-coding RNAs (lncRNAs) in GC remains poorly understood. This study used data from the Cancer Genome Atlas (TCGA) and previous research to identify NETs-related lncRNAs in GC. A prognostic signature comprising four NETs-related lncRNAs (NlncSig) was developed and validated, serving as a predictor for patient survival and response to immunotherapy. The NlncSig was correlated with poorer outcomes in high-risk patients and demonstrated that those with lower risk scores exhibited more favorable responses to immunotherapy. In vitro experiments confirmed that LINC01150 enhances GC cell proliferation, migration, and invasion. This robust NlncSig provides a reliable tool for predicting survival and immune characteristics in GC, with the potential to guide personalized therapeutic approaches and improve patient care.

Ferroptosis plays a crucial role in the pathogenesis of osteoarthritis (OA), and inhibition of chondrocyte ferroptosis effectively alleviates OA progression. Krüppel-like factor 9 (KLF9) is demonstrated to be upregulated in OA, but its molecular mechanism remains unclear. The study aimed to investigate the role of KLF9 in OA progression. Primary chondrocytes were treated with IL-1β to establish an OA cell model, and showed that KLF9 was highly expressed in IL-1β-incubated chondrocytes. Knockdown of KLF9 alleviated IL-1β-induced chondrocyte degeneration. In addition, chondrocytes treated with IL-1β showed a decreased methylation proportion in the KLF9 gene promoter. DNA methyltransferase 1 (DNMT1) directly bound to the KLF9 promoter, and overexpression of DNMT1 inhibited KLF9 expression by promoting its promoter methylation in chondrocytes. Subsequently, KLF9 shRNA and pcDNA-CYP1B1 were individually or altogether transfected into chondrocytes. KLF9 shRNA inhibited Cytochrome P450 1B1 (CYP1B1) expression in chondrocytes, and pcDNA-CYP1B1 abrogated the inhibitory effect of KLF9 shRNA on IL-1β-induced chondrocyte ferroptosis. Moreover, Ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) reversed the promotion of pcDNA-CYP1B1 on IL-1β-induced chondrocyte ferroptosis. Finally, in vivo experiments showed that KLF9 shRNA significantly suppressed the cartilage tissue damage, ferroptosis, and the IHC scores of KLF9 and CYP1B1 in rats. In conclusion, our results suggested that KLF9, epigenetic silenced by DNMT1, promoted extracellular signal-regulated kinase (ERK)-mediated ferroptosis of OA chondrocytes through transcriptionally regulating CYP1B1. Thus, KLF9 is expected to be a new target for the treatment of OA.

Air pollution, especially from ultrafine particles (PM0.1, ≤0.1 μm), is increasingly recognized for its detrimental effects on health. The influence of PM0.1 on neurodevelopmental disorders and its underlying mechanisms remain incompletely understood but are of significant concern. Through an investigation using mouse embryonic stem cells (mESCs), our study has uncovered disruptions in cell cycle dynamics, reduced neural precursor formation, and impaired neurogenesis during mESC neural differentiation as a result of PM0.1-induced neurodevelopmental toxicity. By employing N6-methyladenosine (m6A) methylated RNA immunoprecipitation sequencing and bioinformatics, we identified Zic1 as a key target of PM0.1-induced developmental disturbances. Our mechanistic findings indicate that PM0.1 enhances m6A methylation of Zic1 by upregulating Mettl3, leading to decreased mRNA stability and expression of this gene. Furthermore, the efficacy of the METTL3 inhibitor in alleviating nerve differentiation impairments emphasizes the significance of this pathway. In addition, source analysis, molecular docking, and toxicity analyses show that PAHs with higher ring structures in PM0.1 from combustion sources competitively bind to METTL3, potentially exacerbating neurodevelopmental toxicity. This study not only underscores the severe impact of PM0.1 on neurodevelopment but also reveals the pivotal role of m6A modification in mediating these effects, providing valuable insights and potential therapeutic targets for mitigating PM0.1-related health risks.

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus, characterized by progressive deterioration of renal structure and function, which may eventually lead to end-stage kidney disease (ESKD). The N6-methyladenosine (m6A) methylation, an important modality of RNA modification, involves three classes of key regulators, writers (e.g., METTL3), erasers (e.g., FTO, ALKBH5) and readers (e.g., YTHDF2), which play important roles in DN. Writers are responsible for introducing m6A modifications on RNAs, erasers remove m6A modifications and readers recognize and bind m6A-modified RNAs to regulate RNAs functions, such as mRNA stability, translation and localization. In DN, abnormal m6A modification may promote kidney injury and proteinuria by regulating key pathways involved in multiple processes, including lipid metabolism and inflammatory response, in kidney cells such as podocytes. Therefore, an in-depth study of the role and mechanism of m6A methylation that are regulated by "writers", "erasers" and "readers" in DN is expected to provide new targets and strategies for the prevention and treatment of DN.

The significance of m6A modifications in several biological processes has been increasingly recognized, particularly in the context of cancer. For instance, m6A modifications in gastric cancer (GC) have been significantly implicated in tumor progression, metastasis, and treatment resistance. GC is characterized by the differential expression of m6A regulators. High expression writers such as METTL3 and WTAP are associated with poor prognosis and aggressive clinical features. Conversely, low expression of METTL14 is linked to worse clinical outcomes, whereas elevated levels of demethylases, such as FTO and ALKBH5, correlate with better survival rates. These m6A regulators influence several cellular biological functions, including proliferation, invasion, migration, glycolysis, and chemotherapy resistance, thereby affecting tumor growth and therapeutic outcomes. The assessment of m6A modification patterns and the expression profiles of m6A-related genes hold substantial potential for improving the clinical diagnosis and treatment of GC. In this review, we provide an updated and comprehensive summary of the role of m6A modifications in GC, emphasizing their molecular mechanisms, clinical significance, and translational applications in developing novel diagnostic and therapeutic strategies.

N6-methyladenosine (m6A) is the most prevalent internal chemical modification in eukaryotic messenger RNA (mRNA), significantly impacting its lifecycle through dynamic and reversible processes involving methyltransferase, demethylase, and binding proteins. These processes regulate mRNA stability, splicing, nuclear export, translation, and degradation. Programmed cell death (PCD), a tightly controlled process encompassing apoptosis, pyroptosis, ferroptosis, autophagy, and necroptosis, plays a crucial role in maintaining cellular homeostasis, tissue development, and function. Recently, m6A modification has emerged as a significant research area due to its role in regulating PCD and its implications in cardiovascular diseases (CVDs). In this review, we delve into the intricate relationship between various PCD types and m6A modification, emphasizing their pivotal roles in the initiation and progression of CVDs such as myocardial ischemia-reperfusion (I/R), atherosclerosis (AS), pulmonary hypertension (PH), cardiomyopathy, doxorubicin (Dox)-induced cardiotoxicity (DIC), heart failure (HF), and myocardial infarction (MI). Our findings underscore the potential of elucidating the roles of m6A and PCD in CVD to pave new pathways for prevention and treatment strategies.

To investigate the potential mechanisms underlying neutrophil extracellular traps (NETs) confer ferroptosis resistance and CD8(+) T cell inhibition in lung adenocarcinoma (LUAD). By the intravenous injection of LLC cells into the tail vein, a LUAD mouse model was created. Phorbol-12-myristate-13-acetate (PMA) stimulated neutrophils to facilitate NETs formation and combined with NETs inhibitor DNase I to explore NETs mechanism on LLC cell proliferation, migration, ferroptosis resistance, and CD8(+) T cell activity. CitH3, myeloperoxidase (MPO), cell-free DNA, and MPO-DNA levels in LUAD were increased, indicating an increase in NETs formation in LUAD. PMA promoted NETs formation in tumours of mice, increased the number of CD3(+)CD4(+) T cells, decreased perforin, granzyme A, granzyme B, IFNγ, and TNF-α levels, and promoted LUAD growth and the number of lung tumour nodules, indicating that PMA promoted NETs formation, reduced the activity of CD8(+)T cells, and promoted LUAD growth. DNase I partially reversed the effects of PMA. NETs promoted LLC cell proliferation and migration, while DNase I reversed NETs effects. Erastin inhibited LLC cell proliferation and migration and promoted ferroptosis. NETs partially reversed Erastin effects. Further results showed that NETs promoted LLC cell proliferation and migration and inhibited ferroptosis by promoting YTHDF2-mediated SLC2A3 mRNA degradation. Sh-YTHDF2 partially reversed the effect of NETs on LLC cells, whereas si-SLC2A3 partially reversed sh-YTHDF2 effects on LLC cells. In addition, NETs inhibited LLC cell ferroptosis by inhibiting CD8(+) T cell activity. Sh-YTHDF2 and DNase I inhibited NETs formation in tumours, increased the activity of CD8(+) T cells and inhibited LUAD growth. Our results suggested that NETs promoted the growth of LUAD through inhibiting ferroptosis and CD8(+) T cell activity by promoting YTHDF2-mediated SLC2A3 mRNA degradation.

Hypoxia is a well-known characteristic of the tumor microenvironment which significantly influences cancer development and is closely linked to unfavorable outcomes. Long noncoding RNAs (lncRNAs), which are part of the noncoding genome, have garnered increasing attention because of their varied functions in tumor metastasis. Long noncoding RNAs (lncRNAs) are defined as noncoding RNAs which are longer than 200 nucleotides, and they regulate diverse cellular processes by modulating gene expression at the transcriptional, post-transcriptional and epigenetic levels. Hypoxia is a well-established environmental factor which enhances the metastasis of solid tumors. Epithelial-mesenchymal transition (EMT) represents one of the key mechanisms triggered by hypoxia which contributes to metastasis. Numerous lncRNAs have been identified as being upregulated by hypoxia. These lncRNAs significantly contribute toward cancer cell migration, invasion and metastasis. Recent studies have identified a crucial role for these hypoxia-induced lncRNAs in chemotherapy resistance. These hypoxia-related lncRNAs can be plausible therapeutic targets for devising effective cancer therapies.

Understanding the heterogeneity of epigenetic modifications within single cells is pivotal for unraveling the nature of the complexity of gene expression and cellular function. In this study, we have developed a strategy based on multichrome encoding and "AND" Boolean logic recognition for multiplexed, spatially resolved imaging of single-cell RNA epigenetic modifications, termed as PRoximity Exchange-assisted Encoding of Multichrome (PREEM). Through the implementation of this strategy, we can now map the expression and nuclear distribution of multiple site-specific RNA N6-methyladenosine (m6A) modifications at the single-molecule resolution level in single-cells, and reveal the previously unknown heterogeneity. Notably, we demonstrate how these patterns change after treatment with various drugs. Moreover, cyclic imaging with tailed DNA self-assembly further suggest the scalability and adaptability of PREEM's design. As an innovative epigenetic modification imaging tool, PREEM not only broadens the horizons of single-cell epigenetics research, enabling joint analysis of multiple targets beyond the limitations of imaging channels, but also reveals cell-to-cell variability, thereby enhancing our capacity to explore cellular functions.

Emerging evidence has shown that the N6-methyladenosine (m6A) modification of RNA plays key roles in tumorigenesis and the progression of various cancers. However, the potential roles of the m6A modification of long noncoding RNAs (lncRNAs) in pancreatic cancer (PaCa) are still unknown. To analyze the prognostic value of m6A-related lncRNAs in PaCa, an m6A-related lncRNA signature was constructed as a risk model via Pearson's correlation and univariate Cox regression analyses in The Cancer Genome Atlas (TCGA) database. The tumor microenvironment (TME), tumor mutation burden, and drug sensitivity of PaCa were investigated by m6A-related lncRNA risk score analyses. We established an m6A-related risk prognostic model consisting of five lncRNAs, namely, LINC01091, AC096733.2, AC092171.5, AC015660.1, and AC005332.6, which not only revealed significant differences in immune cell infiltration associated with the TME between the high-risk and low-risk groups but also predicted the potential benefit of immunotherapy for patients with PaCa. Drugs such as WZ8040, selumetinib, and bortezomib were also identified as more effective for high-risk patients. Our results indicate that the m6A-related lncRNA risk model could be an independent prognostic indicator, which may provide valuable insights for identifying therapeutic approaches for PaCa.

A new type of nonapoptotic, iron-dependent cell death induced by lipid peroxidation is known as ferroptosis. Numerous pathological processes, including inflammation and cancer, have been demonstrated to be influenced by changes in the ferroptosis-regulating network. Long non-coding RNAs (LncRNAs) are a group of functional RNA molecules that are not translated into proteins, which can regulate gene expression in various manners. An increasing number of studies have shown that lncRNAs can interfere with the progression of ferroptosis by modulating ferroptosis-related genes directly or indirectly. Despite evidence implicating lncRNAs in cancer and inflammation, studies on their mechanisms and therapeutic potential remain scarce. We investigate the mechanisms of lncRNA-mediated regulation of inflammation and cancer immunity, assessing the feasibility and challenges of lncRNAs as therapeutic targets in these conditions.

N(6)-methyladenosine (m6A) modification is the most abundant and prevalent internal modification in eukaryotic mRNAs. The role of m6A modification in cancer has become a hot research topic in recent years and has been widely explored. m6A modifications have been shown to regulate cancer occurrence and progression by modulating different target molecules. This paper reviews the recent research progress of m6A modifications in cancer and provides an outlook on future research directions, especially the development of molecularly targeted drugs. See also the graphical abstract(Fig. 1).

The N6-methyladenosine (m6A) modification serves as an essential epigenetic regulator in eukaryotic cells, playing a significant role in tumorigenesis and cancer progression. However, the detailed biological functions and underlying mechanisms of m6A regulation in gastric cancer (GC) are poorly understood. Our research revealed that the m6A demethylase ALKBH5 was markedly downregulated in GC tissues, which was associated with poor patient prognosis. Functional studies demonstrated that suppressing ALKBH5 expression enhanced GC cell proliferation, migration, and invasion. Mechanistically, ALKBH5 removed m6A modifications from the 5' uncapped and polyadenylated transcripts (UPTs) of WRAP53. This demethylation decreased WRAP53 stability and translation efficiency. The lower level of WRAP53 disrupts the interaction between USP6 and RALBP1 protein, promoting RALBP1 degradation and thereby suppressing the PI3K/Akt/mTOR signaling cascade, ultimately attenuating the progression of GC. These findings highlight the pivotal role of ALKBH5-mediated m6A demethylation in inhibiting GC progression and the potential role of ALKBH5 as a promising biomarker and therapeutic target for GC intervention.

Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation. This process is regulated by signaling pathways associated with redox balance, iron metabolism, and lipid metabolism. Cancer cells' increased iron demand makes them especially susceptible to ferroptosis, significantly influencing cancer development, therapeutic response, and metastasis. Recent findings indicate that cancer cells can evade ferroptosis by downregulating key signaling pathways related to this process, contributing to drug resistance. This underscores the possibility of modulating ferroptosis as an approach to counteract drug resistance and enhance therapeutic efficacy. This review outlines the signaling pathways involved in ferroptosis and their interactions with cancer-related signaling pathways. We also highlight the current understanding of ferroptosis in cancer drug resistance, offering insights into how targeting ferroptosis can provide novel therapeutic approaches for drug-resistant cancers. Finally, we explore the potential of ferroptosis-inducing compounds and examine the challenges and opportunities for drug development in this evolving field.

RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such as N6-methyladenosine (m6A) and 5-methylcytosine (m5C), are implicated in various cellular processes. These modifications are regulated by proteins that write, erase, and read RNA and modulate RNA stability, splicing, translation, and degradation. Recent studies have highlighted their roles in metabolic reprogramming, signaling pathways, and cell cycle control, which are essential for tumor proliferation and survival. Despite these scientific advances, the precise mechanisms by which RNA modifications affect cancer remain inadequately understood. This review comprehensively examines the role RNA modifications play in cancer proliferation, metastasis, and programmed cell death, including apoptosis, autophagy, and ferroptosis. It explores their effects on epithelial-mesenchymal transition (EMT) and the immune microenvironment, particularly in cancer metastasis. Furthermore, RNA modifications' potential in cancer therapies, including conventional treatments, immunotherapy, and targeted therapies, is discussed. By addressing these aspects, this review aims to bridge current research gaps and underscore the therapeutic potential of targeting RNA modifications to improve cancer treatment strategies and patient outcomes.

Colorectal cancer (CRC) is an aggressive malignancy among malignant tumours, with a high incidence globally. LINC01614, a long non-coding RNA, has been identified as an essential regulator in multiple cancer types. However, its biological functions and underlying molecular mechanisms in CRC remain largely unknown.

In this study, we employed RT-qPCR to assess the expression levels of LINC01614 in CRC samples. In vitro, glucose metabolism experiments were conducted to evaluate glucose metabolism in cells. The binding relationship between miR-4443, PFKFB3, and LINC01614 was confirmed through fluorescence reporter gene detection. The subcellular localization of LINC01614 in CRC cells was determined using FISH and subcellular fractionation experiments. Additionally, a mouse subcutaneous tumor model was established for in vivo experiments.

Our findings reveal that LINC01614 is upregulated in CRC tissues. Silencing of LINC01614 suppresses the malignant behaviors of CRC cells, including cell proliferation, invasion, migration, and aerobic glycolysis. Furthermore, we discovered that LINC01614 promotes the expression of PFKFB3. Additional experiments demonstrated that LINC01614 binds to miR-4443, leading to the upregulation of PFKFB3 expression. Further experiments confirmed that the LINC01614/miR-4443/PFKFB3 axis promotes CRC cell malignancy by enhancing aerobic glycolysis. Additionally, we found that STAT1 promotes the transcription of LINC01614.

These findings uncover a novel regulatory pathway wherein STAT1-induced LINC01614 enhances PFKFB3 expression by sponging miR-4443, thereby accelerating CRC development. This understanding may lead to novel therapeutic strategies for CRC treatment.

Hepatic fibrosis (HF) is an abnormal reparative response of the liver to chronic injury and is histologically reversible. In recent years, increasing interest has been given to changes in m 6A in liver disease. In this study, we explore the role of the m 6A-modified reading protein YTHDF2 in HF and its regulatory mechanism. The HF mouse model is generated through CCl 4 injection, and the cell model is via TGF-β stimulation. The liver tissues are subjected to hematoxylin-eosin, Masson, and α-SMA immunohistochemical staining. Reactive oxygen species (ROS) and iron levels are examined via relevant kits. Quantitative real-time PCR, immunofluorescence staining, and western blot analysis were conducted to measure the YTHDF2 and ACSL4 levels. RNA immunoprecipitation, methylated RNA immunoprecipitation, RNA pull-down, and polysome fractionation were performed to understand the regulatory mechanism by which YTHDF2 affects ACSL4. The results show that YTHDF2 is highly expressed after HF induction, and the inhibition of YTHDF2 reduces fibrosis as well as ROS and iron levels. In vitro, overexpression of YTHDF2 increases hepatic stellate cell activation, as well as ROS and iron levels, and this effect is blocked by the silencing of ACSL4. YTHDF2 acts as a regulator of ACSL4 expression and is involved in m 6A modification. In addition, in vivo experiments indicate that overexpression of ACSL4 reverses the attenuating effect of YTHDF2 interference on HFs. Therefore, YTHDF2 mediates the expression of the ferroptosis marker protein ACSL4 in an m 6A-dependent manner, thereby affecting HF.

Targeting ferroptosis pathway becomes a new solution for cisplatin (DDP) resistance in lung adenocarcinoma (LUAD), and further research is required to explore the molecular mechanisms underlying ferroptosis and DDP resistance, providing biotargets for LUAD treatment. In this study, DDP-sensitive A549 cells and DDP-resistant A549/DDP cells were treated with DDP, DDP sensitivity was detected through using CCK-8 method and colony formation assay, ferroptosis-related markers were determined through commercial kits, and the molecular regulatory mechanism was analyzed through methylated RNA immunoprecipitation, RNA pull-down, dual luciferase assay, quantitative real-time polymerase chain reaction and western blotting assay. Results showed that compared to A549 cells, FENDRR was downregulated in A549/DDP cells, and FENDRR increased iron content, labile iron pool, lipid peroxidation, LDH release and ROS levels, accelerating ferroptosis to promote DDP sensitivity. Interestingly, we found that METTL3-mediated N6-methyladenosine modification YTHDF2 dependently resulted in FENDRR degradation, and FENDRR overexpression elevated TFRC expression through sponging miR-761. Mechanistically, METTL3 inhibited the FENDRR/TFRC axis to alleviate DDP-induced ferroptosis, promoting DDP resistance in LUAD cells. Collectively, our findings identify a novel molecular regulatory mechanism in DDP resistance of LUAD, and suggest that FENDRR might be an attractive target for addressing DDP resistance.

Methylation modification is a crucial epigenetic alteration encompassing RNA methylation, DNA methylation, and histone methylation. Ferroptosis represents a newly discovered form of programmed cell death (PCD) in 2012, which is characterized by iron-dependent lipid peroxidation. The comprehensive investigation of ferroptosis is therefore imperative for a more profound comprehension of the pathological and pathophysiological mechanisms implicated in a wide array of diseases. Researches show that methylation modifications can exert either promotive or inhibitory effects on cell ferroptosis. Consequently, this review offers a comprehensive overview of the pivotal role played by methylation in ferroptosis, elucidating its associated factors and underlying mechanisms.

Danggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood.

The present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics.

DGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism.

DGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F2α (PGF2α)/PGE2, uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA2, LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND.

Our findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.

Ferroptosis, a recently recognized form of regulated cell death (RCD) characterized by iron-dependent lipid peroxide accumulation, has emerged as a noteworthy regulator in various bone-related diseases, including osteoporosis (OP), osteoarthritis (OA), and osteosarcoma (OS). OS primarily afflicts the elderly, rendering them susceptible to fractures due to increased bone fragility. OA represents the most prevalent arthritis in the world, often observed in the aging population. OS predominantly manifests during adolescence, exhibiting an aggressive nature and bearing a significantly unfavorable prognosis. In this review article, we present an overview of the characteristics and mechanism of ferroptosis and its involvement in bone-related diseases, with a particular focus on OP, OA, and OS. Furthermore, we summarize chemical compounds or biological factors that impact bone-related diseases by regulating ferroptosis. Through an in-depth exploration of ferroptosis based on current research findings, this review provides promising insights for potential therapeutic approaches to effectively manage and mitigate the impact of these bone-related pathological conditions.

Cisplatin resistance is the leading cause of mortality in muscle-invasive bladder cancer (MIBC) cases. Previous evidence suggests that abnormal epitranscriptome modifications are associated with reduced chemotherapy responses. However, the exact underlying mechanism remains largely unknown.

Insulin-like growth factor-2 mRNA-binding protein 2 (IMP2) was identified by clustered regularly interspaced short palindromic repeats (CRISPR) data screening, single-cell RNA-sequencing and sample analysis. To evaluate the regulatory role of IMP2, functional studies were conducted both in vitro and in vivo. To elucidate the underlying mechanisms, various techniques including immunofluorescence, fluorescent in situ hybridization, RNA pull-down, coimmunoprecipitation, and RNA immunoprecipitation were used.

Our study revealed that IMP2 was overexpressed in chemoresistant MIBC and lung metastasis tissues. IMP2 inhibition markedly enhanced the sensitivity of BC cells to cisplatin both in vitro and in vivo. Mechanistically, IMP2 enhanced the mRNA stability of IPO4 and SLC7A11 in a m6A-dependent manner, augmenting the nuclear translocation of C/EBPδ to activate PRKDC-mediated DNA damage repair in response to cisplatin. Moreover, IMP2 upregulated SLC7A11 levels and suppressed cisplatin-induced ferroptosis. Combining ferroptosis and apoptosis inhibitors completely reversed cisplatin resistance caused by IMP2 overexpression. LINC00941, which was induced by HIF-1α-mediated transcriptional activation, specifically bound IMP2 and protects it from degradation.

This work demonstrated a novel mechanism involving the IMP2-IPO4/SLC7A11 pathway as a promising treatment target for cisplatin-resistant bladder cancer.

Osteoarthritis (OA) is a prevalent degenerative disease in elderly people that is characterized by cartilage loss and abrasion, leading to joint pain and dysfunction. The aetiology of OA is complicated and includes abnormal mechanical stress, a mild inflammatory environment, chondrocyte senescence and apoptosis, and changes in chondrocyte metabolism. Ferroptosis is a regulated cell death modality characterized by the excessive accumulation of lipid peroxidation and mitochondrial dysfunction. The role of ferroptosis in OA pathogenesis has aroused researchers' attention in the past two years, and there is mounting evidence indicating that ferroptosis is destructive. However, the impact of ferroptosis on OA and how the regulators of ferroptosis affect OA development are unclear. Here, we reviewed the current understanding of ferroptosis in OA pathogenesis and summarized several drugs and compounds targeting ferroptosis in OA treatment. The accumulation of intracellular iron, the trigger of Fenton reaction, the excessive production of ROS, the peroxidation of PUFA-PLs, and mitochondrial and membrane damage are involved in chondrocyte ferroptosis. System Xc - and GPX4 are the most important regulators that control ferroptosis. Several compounds, such as DFO and Fer-1, have been proven effective in preventing ferroptosis and slowing OA progression on animal models. Collectively, targeting ferroptosis shows great potential in treating OA.

Cancer is a disease that poses a serious threat to human health, the occurrence and development of which involves complex molecular mechanisms. Long non‑coding RNAs (lncRNAs) and RNA‑binding proteins (RBPs) are important regulatory molecules within cells, which have garnered extensive attention in cancer research in recent years. The binding of lncRNAs and RBPs plays a crucial role in the post‑transcriptional regulation of mRNA, affecting the synthesis of proteins related to cancer by regulating the stability of mRNA. This, in turn, regulates the malignant biological behaviors of tumor cells, such as proliferation and metastasis, and serves an important role in therapeutic resistance. The present study reviewed the role of lncRNA‑RBP interactions in the regulation of mRNA stability in various malignant tumors, with a focus on the molecular mechanisms underlying this regulatory interaction. The aim of the present review was to gain a deeper understanding of these molecular mechanisms to provide new strategies and insights for the precise treatment of cancer.

Propofol has become a microtubule-stabilizing drug for prostate cancer (PC) therapy, but propofol resistance impairs the therapeutic effect. This study aimed to explore the regulatory mechanism of propofol in the pathogenesis of PC through mechanisms involving N6-methyladenosine (m6A) modification. The changes in PC cell malignancy were evaluated by means of transwell, cell counting kit 8 (CCK-8), western blotting and tumour xenograft model assays. Long noncoding RNA TRHDE-AS1 and m6A methyltransferase METTL14 expression levels were determined via reverse transcription quantitative polymerase chain reaction (RT-qPCR). The m6A modification of TRHDE-AS1 which was mediated by METTL14 was confirmed by conducting methylated RNA immunoprecipitation (MeRIP) assay. We observed that propofol (200 μM) inhibited PC cell malignancy in vivo and in vitro, elucidating that it impaired cell proliferation, migration and tumour growth but induced apoptosis. TRHDE-AS1 expression was observed to be lower in PC cells and tissues, and propofol induced TRHDE-AS1 upregulation in PC cells. Propofol was capable of reversing the tumour-promoting effect of TRHDE-AS1 knockdown in PC cells. Additionally, METTL14 was upstream of TRHDE-AS1 to induce m6A modification of TRHDE-AS1 in PC cells. Collectively, our results show that propofol prevents PC progression by upregulating TRHDE-AS1 expression and METTL14 is involved in the m6A modification of TRHDE-AS1. These findings suggest that TRHDE-AS1 may be a potential therapeutic target for the improvement of propofol's therapeutic effect.

Our previous research revealed the apoptosis-inhibiting effect of lncRNA FAM230B in gastric cancer (GC). While its role on ferroptosis of GC remain unexplored. In this study, the m6A level and RNA stability regulation of METTL3 on FAM230B was detected by m6A quantification, stability assays, MeRIP, and their interaction was confirmed by RIP, and RNA pull-down assays. The level of ferroptosis was detected by flow cytometry, MDA and GSH level assessments, and electron microscopy. Gene expression was detected by quantitative real-time PCR, western blot, and immunofluorescence. The miR-27a-5p and BTF3 interaction was predicted with TargetScan and confirmed by dual-luciferase assay. Here, elevated levels of METTL3 and FAM230B were observed in GC tissues and cell lines. METTL3 was confirmed to bind with FAM230B RNA. Furthermore, silencing METTL3 reduced FAM230B m6A levels and stability, leading to decreased FAM230B and increased miR-27a-5p expressions. FAM230B knockdown favored ferroptosis and increased BTF3 expression, while its overexpression mitigated erastin-induced ferroptosis in GC cells. Additionally, BTF3 overexpression was found to negate miR-27a-5p's ferroptosis-promoting effects in GC cells. Collectively, our study demonstrates that the m6A modification of FAM230B by METTL3 plays a crucial role in promoting GC progression by reducing ferroptosis, through the modulation of the miR-27a-5p/BTF3 axis.

The fifth most frequent cancer in the world is gastric cancer. It ranks as the fourth most common reason for cancer-related deaths. Even though surgery is the only curative treatment for stomach cancer, adding adjuvant radiotherapy and chemotherapy is preferable than only surgery. The majority of patients, however, are discovered to be extremely tardy the first time and have a terrible prognosis. Therefore, it is necessary to create more viable therapy modalities. A growing number of studies in recent years have shown that ferroptosis and many cancer types are related. This gives our treatment a fresh viewpoint. We investigated the relationship between different signal pathways and non-coding RNA on ferroptosis in gastric cancer cells. Also discussed the targets cause ferroptosis resistance increased or reduced to the influence of the chemoresistance,proliferation and metastasis.

Wound healing is a complex process involving sequential stages of hemostasis, inflammation, proliferation, and remodeling. Multiple cell types and factors, including underlying conditions like diabetes and bacterial colonization, can influence healing outcomes and scar formation. N6-methyladenosine (m6A), a predominant RNA modification, plays crucial roles in gene expression regulation, impacting various biological processes and diseases. m6A regulates embryonic skin morphogenesis, wound repair, and pathophysiological processes like inflammation and angiogenesis. Recent studies have highlighted the role of m6A in wound healing, scar formation, and tissue remodeling. Additionally, m6A presents a unique expression pattern in pathological wounds and scars, potentially influencing wound healing and scar formation through modulating gene expression and cellular signaling, thereby serving as potential biomarkers or therapeutic targets. Targeting m6A modifications are potential strategies to enhance wound healing and reduce scar formation. This review aims to explore the roles and mechanisms of m6A RNA methylation in wound healing and scars, and discuss current challenges and perspectives. Continued research in this field will provide significant value for optimal wound repair and scar treatment.

Cancer development is thought to be closely related to aberrant epigenetic regulation, aberrant expression of specific non-coding RNAs (ncRNAs), and tumor microenvironment (TME). The m6A methylation is one of the most abundant RNA modifications found in eukaryotes, and it can determine the fate of RNA at the post-transcriptional level through a variety of mechanisms, which affects important biological processes in the organism. The m6A methylation modification is involved in RNA processing, regulation of RNA nuclear export or localisation, RNA degradation and RNA translation. This process affects the function of mRNAs and ncRNAs, thereby influencing the biological processes of cancer cells. TME accelerates and promotes cancer generation and progression during tumor development. The m6A methylation interacting with ncRNAs is closely linked to TME formation. Mutual regulation and interactions between m6A methylation and ncRNAs in TME create complex networks and mediate the progression of various cancers. In this review, we will focus on the interactions between m6A modifications and ncRNAs in TME, summarising the molecular mechanisms by which m6A interacts with ncRNAs to affect TME and their roles in the development of different cancers. This work will help to deepen our understanding of tumourigenesis and further explore new targets for cancer therapy.

Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltransferase. The purpose of this study was to explore the specific mechanism of WTAP in asthma progression, and clarify the intricate interplay between m6A modifications, WTAP, AXIN1, and their collective impact on airway smooth muscle cells (ASMCs) proliferation in asthma. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were used to establish an asthma model in vitro. The cell phenotype was tested using CCK-8, transwell, and wound healing assays. The expression of the Wnt signalling pathway was detected by western blotting. In addition, the relationship between WTAP/YTDHF2 and AXIN1 was assessed by a double luciferase reporter assay. Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1. We found that WTAP was significantly increased in PDGF-BB-treated ASMCs. Knockdown of WTAP inhibited the excessive cell viability and migration of ASMCs induced by PDGF-BB. Furthermore, WTAP knockdown increased AXIN1 levels and inhibited the Wnt signalling pathway. Furthermore, WTAP knockdown decreased the m6A levels and enhanced the mRNA stability of AXIN1. WTAP overexpression showed the opposite effect. In addition, YTHDF2 was demonstrated to be the reader that recognizes the WTAP-mediated m6A modification of AXIN1. YTHDF2 knockdown enhanced the mRNA stability of AXIN1 and reversed the effect of WTAP overexpression on PDGF-BB-treated ASMCs. WTAP knockdown inhibited the excessive cell viability and migration of ASMCs by enhancing the m6A levels of AXIN1, which was further recognized by YTHDF2. The upregulation of AXIN1 mediated by the WTAP/YTHDF2 axis further inhibited the Wnt signalling pathway. Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms.

The emerging data compiled during the past five years on 3-deazaneplanocin (DZNep) provide compelling evidence to reevaluate this drug as a better alternative over the specific catalytic inhibitors of histone methyl transferases (HTMs). The indirect mechanism of DZNep via inhibition of AdoHcy-ase, once considered a liability due to possible side effects, has now shown to be rather beneficial as additional pathways targeted by DZNep are important contributors to its superior anticancer properties. Furthermore, DZNep has demonstrated the ability to induce proteasomal degradation of its target and reduce toxicity in combination with well-established antitumor therapies in animal models. In addition, DZNep has shown important effects in suppressing fibrosis and inflammation in liver, kidney, peritoneum, and airways. Finally, inhibition of mRNA m6A methylation by DZNep suppresses the synthesis of the viral genome in SARS-Cov-2 infection and promises to have important therapeutic value when combined with its potent antiviral efficacy and anti-inflammatory effects.