Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a critical player in cancer pathogenesis. Concurrently, inflammation, a key biological response to tissue injury or infection, significantly influences cancer development and progression. The interplay between ferroptosis and inflammation represents a promising yet underexplored area of research. This review synthesizes recent advances in understanding the molecular mechanisms governing their interaction, emphasizing how ferroptosis triggers inflammatory responses and how inflammatory mediators, such as TNF-α, regulate ferroptosis through iron metabolism and lipid peroxidation pathways. Key molecular targets within the ferroptosis-inflammation axis, including GPX4, ACSL4, and the NF-κB signaling pathway, offer therapeutic potential for cancer treatment. By modulating these targets, it may be possible to enhance ferroptosis and fine-tune inflammatory responses, thereby improving therapeutic outcomes. Additionally, this review explores the broader implications of targeting the ferroptosis-inflammation interplay in disease treatment, highlighting opportunities for developing innovative strategies to combat cancer. By bridging the gap in current knowledge, this review provides a comprehensive resource for researchers and clinicians, offering insights into the therapeutic potential of this intricate biological relationship.

Basal cell carcinoma (BCC) is a highly invasive and metastatic non-melanoma skin tumor. Traditional treatments, such as surgery, radiation, and chemotherapy, often result in severe side effects. Recent advances in RNA interference (RNAi) have highlighted its potential in targeting cancer-causing genes. To address the complex pathology of BCC, we developed a multifunctional gene delivery system using benzylthio-modified dendritic polylysine nanoparticles loaded with siDNMT1 (siDNMT1@PDPs). This system exhibits excellent dispersibility, with over 85% of particles measuring between 50 and 80 nm, and high stability, with a zeta potential of +57.10 mV. This design enables efficient penetration into tumor cells and controlled release of siDNMT1 in the tumor microenvironment (TME), thereby improving therapeutic outcomes. Our results demonstrate that siDNMT1@PDPs significantly inhibit tumor progression and metastasis in BCC by reducing AXIN2 promoter methylation, thereby increasing AXIN2 expression. Compared to existing treatments, siDNMT1@PDPs exhibit superior biocompatibility, both in vitro and in vivo, and provide a more targeted and effective therapeutic approach. These findings suggest that siDNMT1@PDPs represent a promising advancement in RNAi-based therapies for BCC, offering potential clinical benefits over current treatment modalities.

The emergence of resistance to antitumor drugs in cancer cells presents a notable obstacle in cancer therapy. Metabolic reprogramming is characterized by enhanced glycolysis, disrupted lipid metabolism, glutamine dependence and mitochondrial dysfunction. In addition to promoting tumor growth and metastasis, metabolic reprogramming mediates drug resistance through diverse molecular mechanisms, offering novel opportunities for therapeutic intervention. Non‑coding RNAs (ncRNAs), a diverse class of RNA molecules that lack protein‑coding function, represent a notable fraction of the human genome. Due to their distinct expression profiles and multifaceted roles in various cancers, ncRNAs have relevance in cancer pathophysiology. ncRNAs orchestrate metabolic abnormalities associated with drug resistance in cancer cells. The present review provides a comprehensive analysis of the mechanisms by which metabolic reprogramming drives drug resistance, with an emphasis on the regulatory roles of ncRNAs in glycolysis, lipid metabolism, mitochondrial dysfunction and glutamine metabolism. Furthermore, the present review aimed to discuss the potential of ncRNAs as biomarkers for predicting chemotherapy responses, as well as emerging strategies to target ncRNAs that modulate metabolism, particularly in the context of combination therapy with anti‑cancer drugs.

Immunotherapy has transformed the landscape of melanoma treatment, offering significant extensions in survival for many patients. Despite these advancements, nearly 50% of melanoma cases remain resistant to such therapies, highlighting the need for novel approaches. Emerging research has identified lipid metabolism reprogramming as a key factor in promoting melanoma progression and resistance to immunotherapy. This reprogramming not only supports tumor growth and metastasis but also creates an immunosuppressive environment that impairs the effectiveness of treatments such as immune checkpoint inhibitors (ICIs). This review delves into the intricate relationship between lipid metabolism and immune system interactions in melanoma. We will explore how alterations in lipid metabolic pathways contribute to immune evasion and therapy resistance, emphasizing recent discoveries in this area. Additionally, we also highlights novel therapeutic strategies targeting lipid metabolism to enhance immune checkpoint inhibitor (ICI) efficacy.

Melanoma, one of the most lethal cancers, demands urgent and effective treatment strategies. However, a successful therapeutic approach requires a precise understanding of the mechanisms underlying melanoma initiation and progression. This review provides an overview of melanoma pathogenesis, identifies current pathogenic factors contributing to mortality, and explores targeted therapy and checkpoint inhibitor therapy. Furthermore, we examine melanoma classification and corresponding therapies, along with advancements in various cell death mechanisms for melanoma treatment. We also discuss the current treatment status along with some drawbacks encountered during research stages such as resistance and metastasis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. And due to the low early diagnostic rate of liver cancer, many patients miss the optimal time for surgical resection, so it is necessitate to identificate the novel therapeutic targets. This study investigates the role of microRNA-6069 (miR-6069) in HCC pathogenesis. We analyzed miR-6069 expression in the TCGA-LIHC cohort, revealing significant upregulation in tumor tissues compared to adjacent normal tissues, and verified it in human tissues. MiR-6069 antisense oligonucleotide(ASO) effectively inhibits HCC cell proliferation in vitro and suppresses subcutaneous HCC tumor growth in nude mice without affecting their weight. Through bioinformatics analysis and immunohistochemistry, we identified PLEKHO1 as a target of miR-6069, and its expression is negatively correlated with miR-6069 expression. Furthermore, using immunohistochemical staining, quantitative PCR (QT-PCR), and Western blot (WB) analysis, we observed that the expression of PLEKHO1 significantly increased in the tumors of nude mice following miR-6069 ASO intervention, and affecting the expression of downstream molecules in the AKT/PI3K signaling pathway. These findings suggest that miR-6069 may influence HCC proliferation by modulating the AKT/PI3K signaling pathway.These findings highlight miR-6069 as a promising therapeutic target in HCC management.

MicroRNAs (miRNAs) hold significant promise as circulating cancer biomarkers and unlike many other molecular markers, they can provide valuable insights that extend beyond tumour biology. The expression of circulating miRNAs may parallel the cellular composition and dynamic activity within the tumour microenvironment and reveal systemic immune responses. The functional complexity of miRNAs-where a single miRNA can regulate multiple messenger RNAs (mRNAs) to fine tune fundamental processes, and a single mRNA can be targeted by multiple miRNAs-underscores their broad significance and impact. However, this complexity poses significant challenges for translating miRNA research into clinical practice. In melanoma, specific miRNA signatures have shown notable diagnostic, prognostic and predictive value, with lineage-specific and immune-related miRNAs frequently identified as valuable markers. In this review, we explore the role of circulating miRNAs as potential biomarkers in melanoma, and highlight the current status and advances required to translate miRNA research into therapeutic opportunities.

Interferon-gamma (IFN-γ) is a cytokine produced mainly by immune cells and can affect cancer cells by modulating the activity of multiple signaling pathways, including the canonical Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT) cascade. In melanoma, IFN-γ can exert both anticancer effects associated with cell-cycle arrest and cell death induction and protumorigenic activity related to immune evasion leading to melanoma progression. Notably, IFN-γ plays a crucial role in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors (ICIs), which are currently used in the clinic. As these agents target programmed death-1 (PD-1) and its ligand (PD-L1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and lymphocyte-activation gene 3 (LAG-3), they are designed to restore the antimelanoma immune response. In this respect, IFN-γ produced by cells in the tumor microenvironment in response to ICIs has a beneficial influence on both immune and melanoma cells by increasing antigen presentation, recruiting additional T-cells to the tumor site, and inducing direct antiproliferative effects and apoptosis in melanoma cells. Therefore, IFN-γ itself and IFN-γ-related gene signatures during the response to ICIs can constitute biomarkers or predictors of the clinical outcome of melanoma patients treated with ICIs. However, owing to its multifaceted roles, IFN-γ can also contribute to developing mechanisms associated with the acquisition of resistance to ICIs. These mechanisms can be associated with either decreased IFN-γ levels in the tumor microenvironment or diminished responsiveness to IFN-γ due to changes in the melanoma phenotypes associated with affected activity of other signaling pathways or genetic alterations e.g., in JAK, which restricts the ability of melanoma cells to respond to IFN-γ. In this respect, the influence of IFN-γ on melanoma-specific regulators of the dynamic plasticity of the cell phenotype, including microphthalmia-associated transcription factor (MITF) and nerve growth factor receptor (NGFR)/CD271 can affect the clinical efficacy of ICIs. This review comprehensively discusses the role of IFN-γ in the response of melanoma patients to ICIs with respect to its positive influence and role in IFN-γ-related mechanisms of resistance to ICIs as well as the potential use of predictive markers on the basis of IFN-γ levels and signatures of IFN-γ-dependent genes.

Ferroptosis is an innovative concept defined as a distinct programmed cell death mode regulated by iron-dependent lipid peroxidation accumulation. This process is governed by numerous energy metabolites such as fatty acids, amino acids and glucose, as well as iron homeostasis. In recent years, increasing studies have been devoted to the crucial effects of ferroptosis in immune cells during the pathogenesis of diseases such as infections, tumours and autoimmune disorders. This review summarises the latest advancements in T-cell ferroptosis, addresses the key components and mechanism of ferroptosis in T cells during inflammatory conditions and tumour progression, and highlights the potential target for treating related diseases. KEY POINTS: Ferroptosis-related mechanisms significantly affect the biology of CD4+ T-cell subsets and are further involved in inflammatory diseases. Crosstalk between CD8+ T cells and tumour cells induces ferroptosis in the tumour microenvironment. Glutathione peroxidase 4 loss promotes regulatory T-cell ferroptosis to enhance anti-tumour immunity.

Melanoma is a highly invasive malignant tumor originating from melanocytes, with increasing incidence in recent years. Ferroptosis is an iron-dependent and non-apoptotic form of programmed cell death characterized by the accumulation of lipid peroxides and reactive oxygen species. Morphologically, ferroptosis exhibits the alteration in cells, such as reduced mitochondrial volume, increased density of bilayer membrane, and a decrease or disappearance of mitochondrial cristae. Ferroptosis has shown tremendous potential and applicability in regulating the development of melanoma. As melanoma progresses, certain biomarkers associated with ferroptosis display characteristic patterns of expression. These changes not only reveal the sensitivity of tumor cells to ferroptosis but also provide potential targets for diagnosis and treatment. Besides, inducing ferroptosis has been well-documented to inhibit the growth of melanoma and enhance the efficacy of tumor immunotherapy. Hence, this review emphasizes the roles and regulatory mechanisms of ferroptosis in melanoma development, the involved immune regulation, as well as the potential for diagnosis and treatment of melanoma. The continuous explorations will endow novel strategies for developing ferroptosis-based therapies for melanoma.

The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC.

MCM-related genes (MCMGs) were identified through The Cancer Genome Atlas (TCGA), The Molecular Signatures Database (MsigDB), and the Mitocarta3.0 databases. Differential gene expression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed using R software to construct a MCM-related model. This model underwent further analysis for somatic mutations, single sample gene set enrichment analysis (ssGSEA), stromal and immune cell estimation, immune checkpoint evaluation, and drug susceptibility prediction to assess the tumor microenvironment (TME) and therapeutic responses. The mRNA expression levels of the genes associated with the model were quantified using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR).

The model, which included six MCMGs (ACADL, ACLY, TXNRD1, DTYMK, ACAT1, and FLAD1), divided all patients (age ≤65 vs. >65 years, P<0.001; male vs. female, ns) into a high-risk group and a low-risk group. The high-risk group showed a higher mortality rate and lower survival rate with AUC of 0.785, 0.752, 0.756, 0.774 and 0.759 for the 1-, 2-, 3-, 4-, and 5-year respectively. A nomogram based on risk score, stage, T, and M had a better prognostic accuracy, with AUC of 0.808, 0.796, 0.811, 0.824 and 0.795 for the 1-, 2-, 3-, 4-, and 5-year respectively. The high-risk group showed enrichment in cell cycle, cell division, and chromosome processes, and a significantly higher tumor mutation burden (TMB) value compared to the low-risk group. Further immune infiltration analysis indicated a significantly reduction in the abundances of some immune cells (activated CD4 T cells, type 2 helper T cells, and neutrophils) and significantly higher expression levels of some immune checkpoint (CD80, CTLA4, HAVCR2, and TNFRSF4) in the high-risk group. Moreover, the risk score was associated with the response to immune checkpoint inhibitors (ICIs) therapy and efficiencies of multiple chemotherapy drugs.

This study developed a prognostic model based on MCMGs, which can predict the prognosis of liver cancer patients and their response to immunotherapy and chemotherapy. The model may provide new strategies to enhance the prognosis and treatment of HCC.

Melanoma is a highly malignant tumor of melanocyte origin that is prone to early metastasis and has a very poor prognosis. Early melanoma treatment modalities are mainly surgical, and treatment strategies for advanced or metastatic melanoma contain chemotherapy, radiotherapy, targeted therapy and immunotherapy. The efficacy of chemotherapy and radiotherapy has been unsatisfactory due to low sensitivity and strong toxic side effects. And targeted therapy is prone to drug resistance, so its clinical application is limited. Melanoma has always been the leader of immunotherapy for solid tumors, and how to maximize the role of immunotherapy and how to implement immunotherapy more accurately are still urgent to be explored. This review summarizes the common immunotherapies and applications for melanoma, illustrates the current research status of melanoma immunotherapy delivery systems, and discusses the advantages and disadvantages of each delivery system and its prospects for clinical application.

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and accounts for about 40% of all lung cancer cases. This research aims to investigate the effects of miR-9-3p on ferroptosis in LUAD cells and to elucidate its regulatory mechanisms. Studies have shown that LUAD is related to ferroptosis, and specific microRNAs (miRNA) are also related to ferroptosis. However, further research is needed to elucidate the mechanisms by which miR-9-3p induces ferroptosis in LUAD.

Our study comprehensively analyzed multiple databases to investigate miR-9-3p expression in LUAD tissues. Quantitative polymerase chain reaction (qPCR) was utilized to detect miR-9-3p levels in LUAD cells and tissues, examining its prognostic significance. Reactive oxygen species (ROS) and superoxide dismutase (SOD) assays assessed the impact of miR-9-3p on lipid peroxidation in LUAD cells. Dual-luciferase reporter assays were conducted to evaluate the binding affinity between miR-9-3p and target genes, while Western blotting and immunofluorescence were used to examine the regulation of miR-9-3p on downstream signaling pathways.

We observed that miR-9-3p was upregulated in LUAD cells by qPCR, and the ferroptosis of LUAD cells increased upon treatment with erastin following the transfection of miR-9-3p inhibitor. Cell Counting Kit-8 (CCK-8), ROS, and SOD activity assays confirmed that inhibiting miR-9-3p enhanced lipid peroxidation in LUAD cells, contributing to higher rates of ferroptosis. Subsequent dual-luciferase reporter assays validated spermidine/spermine N1-acetyltransferase 1 (SAT1) as a target gene of miR-9-3p. Further Western blot confirmed that miR-9-3p regulated the expression of SAT1 and p53 proteins in p53 wild-type (WT) LUAD cells. Rescue experiments demonstrated that SAT1 was necessary for miR-9-3p to promote cell proliferation and suppress ferroptosis in p53 WT LUAD cells. Additionally, the effect of miR-9-3p on ferroptosis in LUAD cells was regulated by p53 signaling pathway.

Overall, these findings demonstrate that miR-9-3p negatively regulates ferroptosis in LUAD cells through SAT1 and p53 signaling pathway, suggesting that miR-9-3p plays a crucial role in LUAD pathogenesis and targeting this miRNA with an inhibitor exhibits promising potential for the treatment of LUAD.

MicroRNAs (miRNAs) emerge as critical regulators of CD8 + T cell function within the complex tumor microenvironment (TME). This review explores the multifaceted interplay between miRNAs and CD8 + T cells across various cancers. We discuss how specific miRNAs influence CD8 + T cell activation, recruitment, infiltration, and effector function. Dysregulation of these miRNAs can contribute to CD8 + T cell exhaustion and immune evasion, hindering anti-tumor immunity. Conversely, manipulating miRNA expression holds promise for enhancing CD8 + T cell activity and improving cancer immunotherapy outcomes. We delve into the role of miRNAs in CD8 + T-cell function across different cancer types, including gliomas, gastric and colon cancer, oral squamous cell carcinoma, thyroid carcinoma, lymphomas, melanoma, breast cancer, renal cell carcinoma, ovarian cancer, uterine corpus endometrial cancer, bladder cancer, acute myeloid leukemia, chronic myelogenous leukemia, and osteosarcoma. Additionally, we explore how extracellular vesicles and cytokines modulate CD8 + T-cell function through complex interactions with miRNAs. Finally, we discuss the potential impact of radiotherapy and specific drugs on miRNA expression and CD8 + T-cell activity within the TME. This review highlights the immense potential of targeting miRNAs to manipulate CD8 + T-cell activity for the development of novel and improved cancer immunotherapies.

Immunotherapies for cancer, specifically immune checkpoint inhibition (ICI), have shown potential in reactivating the body's immune response against tumors. However, there are challenges to overcome in addressing drug resistance and improving the effectiveness of these treatments. Recent research has highlighted the relationship between ferroptosis and the immune system within immune cells and the tumor microenvironment (TME), suggesting that combining targeted ferroptosis with immunotherapy could enhance anti-tumor effects. This review explores the potential of using immunotherapy to target ferroptosis either alone or in conjunction with other therapies like immune checkpoint blockade (ICB) therapy, radiotherapy, and nanomedicine synergistic treatments. It also delves into the roles of different immune cell types in promoting anti-tumor immune responses through ferroptosis. Together, these findings provide a comprehensive understanding of synergistic immunotherapy focused on ferroptosis and offer innovative strategies for cancer treatment.

The response of gastric cancer (GC) patients to first-line programmed cell death 1 (PD-1) blockade and S-1 plus oxaliplatin (SOX) chemotherapy varies considerably, and the underlying mechanisms driving this variability remain elusive. Exosomal microRNAs (miRNAs or miRs) have emerged as potential biomarkers for efficacy prediction due to their roles in GC biology and stable expression in serum. In this study, we aimed to identify biomarkers to predict patients' response to anti-PD-1 therapy and further elucidate the potential mechanisms by which these exosomal miRNAs modulate the immune response in GC.

Serum exosomes were extracted from 11 GC patients (five in the primary cohort and six in the validation cohort) treated with SOX and camrelizumab (a PD-1 inhibitor). High-throughput sequencing was performed to identify miRNA expression profiles, after which hierarchical clustering and a differential expression analysis were conducted. Functional enrichment analyses of the target genes for the significantly upregulated miRNAs were performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The validation of the candidate miRNAs was carried out by quantitative polymerase chain reaction (qPCR) in an independent cohort.

MiRNA sequencing identified 3,083 miRNAs, of which 74 (42 upregulated and 32 downregulated) were differentially expressed between the responders and non-responders. The GO and KEGG pathway analyses of the top 20 upregulated miRNAs indicated that the target genes were significantly involved in transcription regulation, cytoplasmic processes, and protein binding, and that key pathways included the PI3K-AKT, MAPK, RAP1, and RAS signaling pathways. Consistent with the sequencing findings, the qPCR validation results showed significant differences in the expression levels of miRNA451a and miRNA142-5p between the responders and non-responders.

This study identified specific plasma exosomal miRNAs in GC patients that differ between responders and non-responders to PD-1 monoclonal antibody therapy combined with chemotherapy. These miRNAs could serve as predictive biomarkers, paving the way for precision medicine and personalized therapy in the treatment of GC.

Ferroptosis, a form of iron-dependent regulated cell death, is characterized by the accumulation of lipid peroxides and distinctive morphological features. Moreover, the reduction of intracellular antioxidant enzyme expression or activity, specifically glutathione peroxidase 4 (GPX4) results in activation of the endogenous pathway of ferroptosis. In this review, we aimed to explore the intricate interplay between microRNAs (miRNAs) and ferroptosis, shedding light on its implications in various disease pathologies. This review delves into the role of miRNAs in modulating key regulators of ferroptosis, including genes involved in iron metabolism, lipid peroxidation, and antioxidant defenses. Furthermore, the potential of targeting miRNAs for therapeutic interventions in ferroptosis-related diseases, such as cancer, neurodegenerative disorders, and ischemia/reperfusion injury, is highlighted.

Immune checkpoint inhibitor (ICI) therapies for tumors of different systems have attained significant achievements and have changed the current situation of tumor treatment due to their therapeutic characteristics of high specificity and low side effects. The immune checkpoint Programmed death 1/Programmed cell death-Ligand 1 (PD-1/PD-L1) axis exerts a vital role in the immune escape of tumor cells. As a result, it has become a key target for tumor immunotherapy. Therefore, to perfect research into potential regulatory factors for the PD-1/PD-L1 axis, in order to understand and illustrate tumor ICI therapy mechanisms, is a significant goal. Moreover, ncRNA has been verified to regulate the PD-1/PD-L1 axis in the tumor immune microenvironment to regulate tumor genesis and development. ncRNAs can improve or decrease the efficacy of ICI therapy by modulating PD-L1 expression. This review aimed to investigate the mechanisms of action of ncRNA in regulating the PD-1/PD-L1 axis in ICI therapy, to provide more efficient immunotherapy for tumors of different systems.

Snakehead vesiculovirus (SHVV) has led to huge economic losses in snakehead aquaculture, and its pathogenic mechanisms is still not fully understood. MicroRNAs (miRNAs), as an important class of non-coding RNAs, play a key regulatory role in the process of viral infection.

We examined the effect of SHVV infection on the expression of miR-130c-5p and the effect of overexpression of miR-130c-5p on the proliferation of SHVV. Cotransfection of viral N protein and miR-130c-5p, and the effect of miR-130c-5p on the expression of N protein was detected. Meanwhile, the effect of overexpression of miR-130c-5p on the expression of various immune factors in the case of viral infection were also tested.

In this study, SHVV infection significantly upregulated the expression of miR-130c-5p in channel catfish ovary (CCO) cells in a time- and dose-dependent manner. The further research revealed that miR-130c-5p mimic significantly inhibited, while its inhibitors promoted SHVV replication. In addition, miR-130c-5p could directly target the viral mRNA of n gene, and overexpression of miR-130c-5p could significantly decrease, and conversely, downregulation of miR-130c-5p could increase the mRNA and protein expression of the viral n gene. Meanwhile, overexpression of miR-130c-5p also upregulated the expression of immune-related genes, such as nucleotide-oligomerization domain (NOD)-like receptor subfamily C3 (NLRC3), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), interleukin-22 (IL-22), and interleukin-1beta (IL-1β) in host cells.

miR-130c-5p was upregulated in the host during SHVV infection, and the upregulated miR-130c-5p directly inhibited viral replication by targeting the n gene of SHVV and promoting viral nucleoprotein degradation. The up-regulated miR-130c-5p also activated the expression of immune-related genes such as NLRC3, MyD88, NF-κB, IL-6, IL-22, and IL-1β, which were involved in the regulation of the signaling pathways including NF-κB, MyD88, Toll-like receptor (TLR), NLR, and janus tyrosine kinase-signal converter and activator of transcription (JAK-STAT), to enhance the host's antiviral immune response, and thus indirectly inhibited the viral proliferation.

MicroRNAs (MIRs) play a crucial role in colorectal cancer (CRC) development and metastasis by regulating immune responses. Tumour-infiltrating lymphocytes (TILs) are an important predictive factor in many cancers, but, their association with microRNAs have not been studied well in colorectal cancer. Three microRNAs (MIR34A, MIR31 & MIR21), the roles of which in tumorigenesis is well-studied and which also possess immunomodulatory effect, were identified by extensive literature search. Of these, MIR34A acts as a tumour suppressor, MIR21 is considered an onco-MIR, and MIR31 displays both tumour-suppressing and oncogenic properties, making it ambiguous. This study examines the relationship between these three micro-RNAs and TILs in CRC.

Conducted over 18 months at a tertiary cancer care hospital in southern India, this unicentric observational study included 69 cases. These cases were analyzed for miR expression using q-RT-PCR, TILs density through hematoxylin & eosin(H&E) slide examination, and p53 and beta-catenin expression via immunohistochemistry (IHC). Correlations between non-parametric variables were assessed using Chi-square and Spearman correlation tests.

The study found significantly higher MIR34A expression in patients aged 60 years and less (26/41, p=0.024) and a higher prevalence of MIR21 in male patients (23/35, p=0.012). TILs at the tumour advancing front were categorized as low (≤10 %) or high (≥15 %). Among the 36 cases with low TILs, high MIR34A and high MIR31 expressions were observed in 24 cases (p=0.016) and 23 cases (p=0.03), respectively. Conversely, 21 of 33 cases with high TILs had low expressions of both MIR34A and MIR31. High TILs were more common in early-stage CRC (TNM stages I-IIIA), with 20 out of 28 cases, compared to 28 of 41 cases in later stages (IIIB-IVC) exhibiting low TILs (p=0.003). Aberrant p53 expression correlated with lower MIR34A levels, consistent with TCGA data.

Lower MIR34A and MIR31 levels are associated with higher TILs density in CRC. Unlike other cancers where MIR34A has anti-tumour effects, there was no statistically significant correlation between its expression and the pT or TNM stages in this study. Increased TILs being a good prognostic indicator, this suggests MIR34A and MIR31 may help CRC cells evade immune surveillance. Aberrant p53 expression downregulates MIR34A, underscoring the therapeutic potential of miRs.

Ferroptosis, distinct from apoptosis, necrosis, and autophagy, is a unique type of cell death driven by iron-dependent phospholipid peroxidation. Since ferroptosis was defined in 2012, it has received widespread attention from researchers worldwide. From a biochemical perspective, the regulation of ferroptosis is strongly associated with cellular metabolism, primarily including iron metabolism, lipid metabolism, and redox metabolism. The distinctive regulatory mechanism of ferroptosis holds great potential for overcoming drug resistance-a major challenge in treating cancer. The considerable role of nanobiotechnology in disease treatment has been widely reported, but further and more systematic discussion on how nanobiotechnology enhances the therapeutic efficacy on ferroptosis-associated diseases still needs to be improved. Moreover, while the exciting therapeutic potential of ferroptosis in cancer has been relatively well summarized, its applications in other diseases, such as neurodegenerative diseases, cardiovascular and cerebrovascular diseases, and kidney disease, remain underreported. Consequently, it is necessary to fill these gaps to further complete the applications of nanobiotechnology in ferroptosis. In this review, we provide an extensive introduction to the background of ferroptosis and elaborate its regulatory network. Subsequently, we discuss the various advantages of combining nanobiotechnology with ferroptosis to enhance therapeutic efficacy and reduce the side effects of ferroptosis-associated diseases. Finally, we analyze and discuss the feasibility of nanobiotechnology and ferroptosis in improving clinical treatment outcomes based on clinical needs, as well as the current limitations and future directions of nanobiotechnology in the applications of ferroptosis, which will not only provide significant guidance for the clinical applications of ferroptosis and nanobiotechnology but also accelerate their clinical translations.

Arsenic is recognized as a hazardous environmental toxicant strongly associated with neurological damage, but the mechanism is ambiguous. Neuronal cell death is one of the mechanisms of arsenic-induced neurological injury. Ferroptosis is involved in the pathophysiological process of many neurological diseases, however, the role and regulatory mechanism of ferroptosis in nerve injury under arsenic exposure remains uncovered. Our findings confirmed the role of ferroptosis in arsenic-induced learning and memory disorder and revealed miR-21 played a regulatory role in neuronal ferroptosis. Further study discovered that miR-21 regulated neuronal ferroptosis by targeting at FTH1, a finding which has not been documented before. We also found an extra increase of ferroptosis in neuronal cells conditionally cultured by medium collected from arsenic-exposed microglial cells when compared with neuronal cells directly exposed to the same dose of arsenic. Moreover, microglia-derived exosomes removal or miR-21 knockdown in microglia inhibited neuronal ferroptosis, suggesting the role of intercellular communication in the promotion of neuronal ferroptosis. In summary, our findings highlighted the regulatory role of miR-21 in ferroptosis and the contribution of microglia-derived miR-21 in exosomes to arsenic-induced neuronal ferroptosis.

Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each.

Small molecular RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), participate in the regulation of gene expression. As powerful regulators, miRNAs, take part in posttranscriptional regulation of gene expression and play important roles in the diagnosis and treatment of cancer. Meanwhile, siRNA can induce sequence-specific gene silencing, thus being able to inhibit tumorigenesis by suppressing the expression of their targeted proto-oncogenes. Small RNAs (including naked miRNAs and siRNAs) are easily degraded by circulating RNAase, which can be retarded through the package of nanoparticles. Therefore, nanoparticles help tumor therapy by regulating targeted genes of small RNAs. Here, we reviewed the effects of small RNAs on gene expression; the advantages, disadvantages, and targeted modification of nanoparticles as carriers transporting small RNAs; and the application of nanocarriers delivering small RNA for cancer-targeted therapy.

Presbycusis, also referred to as age-related hearing loss (ARHL), is a multifaceted condition caused by the natural aging process affecting the auditory system. Genome-wide association studies (GWAS) in human populations can identify potential genes linked to ARHL. Despite this, our knowledge of the biochemical and molecular mechanisms behind the condition remains incomplete. This study aims to evaluate a potential protective tool for ARHL treatment by comparing human blood-based target gene-miRNA associations regulated in ARHL. To identify promising target genes for ARHL, we utilized an mRNA assay. To determine the role of miRNA in ARHL, we investigated the expression profile of miRNA in whole blood in ARHL patients with real-time polymerase chain reaction (RT-qPCR). A reporter gene assay was performed to confirm the regulation of candidate genes by microRNA. Through RT-qPCR validation analysis, we finally confirmed the relationship between ARHL and the role of the interferon-gamma (IFNG) gene. This gene can be regarded as an age-related gene. Through gene ontology (GO) analysis, it has been found that these genes are enriched in pathways related to apoptosis. Among them, IFNG induces an inflammatory response, apoptotic cell death, and cellular senescence. We found that miR-409-3p downregulates the expression of the IFNG in vitro. In addition, the downregulation of the IFNG by miRNA 409-3p promoted cell apoptosis and suppressed proliferation. In conclusion, our study produced gene signatures and associated microRNA regulation that could be a protective key for ARHL patients. IFNG genes and miR-409-3p should be investigated for their usefulness as a new biomarker for treatment modality.

Gold nanoparticles (AuNPs) have become the rising stars in the field of nanotechnology and made a revolution in exploiting the profundity of genomics due to their distinguished properties such as stability, ease in preparation and conjugation, biocompatibility, and unique optical properties. These characteristics have greatly expanded their applications such as sensitive and selective quantitation of nucleic acids and as effective carriers for specifically delivering various important molecules/biomolecules to various targets, which are the cornerstone in treating genetic disorders. This review comprehensively discusses the most recent progress in utilization of AuNPs in quantitation and delivery of nucleic acids. The future prospects and challenges of various methods have also been illustrated. It is believed that researchers will continue to overcome the limitations in previous approaches and AuNPs will still play vital roles in the development of diagnosis and treatment of gene-related diseases.

Ferroptosis-mediated multimodal therapy has emerged as a promising strategy for tumor elimination, with lipid peroxide (LPO) playing a pivotal role. However, the therapeutic efficiency is limited due to insufficient intracellular levels of free fatty acids (FFA), which severely hinder the production of LPO. To address this limitation, we proposed a lipophagy strategy aimed at degrading lipid droplets (LDs) to release FFA, serving as the essential "fuel" for LPO production. In this study, the lipophagy inducer epigallocatechin gallate (EGCG) was self-assembled with reactive oxygen species (ROS)-producer phenethyl isothiocyanate (PEITC) mediated by Fe2+ to form EFP nanocapsules, which were further integrated into microneedle patches to form a "all-in-one" EFP@MNs. The metal-polyphenol network structure of EFP endow it with photothermal therapy capacity. Upon insertion into tumors, the released EFP nanocapsules were demonstrated to induce lipophagy through metabolic disturbance, thereby promoting LPO production and facilitating ferroptosis. When combined with photothermal therapy, this approach significantly remolded the tumor immune microenvironment by driving tumor-associated macrophages toward M1 phenotype and enhancing dendritic cell maturation. Encouragingly, in conjunction with αPD-L1 treatment, the proposed EFP@MNs exhibited remarkable efficacy in tumor ablation. Our study presents a versatile framework for utilizing microneedle patches to power ferroptosis-mediated multimodal therapy.

The balance of programmed cell death (PCD) mechanisms, including apoptosis, autophagy, necroptosis and others, is pivotal in cancer progression and treatment. Dysregulation of these pathways results in uncontrolled cell growth and resistance to conventional therapies. Nanomedicine offers a promising solution in oncology through targeted drug delivery enabling precise targeting of cancer cells while preserving healthy tissues. This approach reduces the side effects of traditional chemotherapy and enhances treatment efficacy by engaging PCD pathways. We details each PCD pathway, their mechanisms, and innovative nanomedicine strategies to activate these pathways, thereby enhancing therapeutic specificity and minimizing harm to healthy tissues. The precision of nanotechnology in targeting PCD pathways promises significant improvements in cancer treatment outcomes. This synergy between nanotechnology and targeted PCD activation could lead to more effective and less toxic cancer therapies, heralding a new era in cancer treatment.

The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, a unique type of regulated cell death, plays a pivotal role in inhibiting tumour growth, presenting new opportunities in treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine cancer cell vulnerability to ferroptosis. In this review, we first summarize the role of chemotherapeutic resistance in cancer growth/development. Then, we summarize the core molecular mechanisms of ferroptosis, its upstream epigenetic regulation, and its downstream effects on chemotherapeutic resistance. Finally, we review recent advances in understanding how ncRNAs regulate ferroptosis and from such modulate chemotherapeutic resistance. This review aims to enhance general understanding of the ncRNA-mediated epigenetic regulatory mechanisms which modulate ferroptosis, highlighting the ncRNA-ferroptosis axis as a key druggable target in overcoming chemotherapeutic resistance.

Melanoma, a lethal form of skin cancer, poses a significant challenge in oncology due to its aggressive nature and high mortality rates. Gold nanostructures, including gold nanoparticles (GNPs), offer myriad opportunities in melanoma therapy and imaging due to their facile synthesis and functionalization, robust stability, tunable physicochemical and optical properties, and biocompatibility. This review explores the emerging role of gold nanostructures and their composites in revolutionizing melanoma treatment paradigms, bridging the gap between nanotechnology and clinical oncology, and offering insights for researchers, clinicians, and stakeholders. It begins by elucidating the potential of nanotechnology-driven approaches in cancer therapy, highlighting the unique physicochemical properties and versatility of GNPs in biomedical applications. Various therapeutic modalities, including photothermal therapy, photodynamic therapy, targeted drug delivery, gene delivery, and nanovaccines, are discussed in detail, along with insights from ongoing clinical trials. In addition, the utility of GNPs in melanoma imaging and theranostics is explored, showcasing their potential in diagnosis, treatment monitoring, and personalized medicine. Furthermore, safety considerations and potential toxicities associated with GNPs are addressed, underscoring the importance of comprehensive risk assessment in clinical translation. Finally, the review concludes by discussing current challenges and future directions, emphasizing the need for innovative strategies to maximize the clinical impact of GNPs in melanoma therapy.

Advances in melanoma research have unveiled critical insights into its genetic and molecular landscape, leading to significant therapeutic innovations. This review explores the intricate interplay between genetic alterations, such as mutations in BRAF, NRAS, and KIT, and melanoma pathogenesis. The MAPK and PI3K/Akt/mTOR signaling pathways are highlighted for their roles in tumor growth and resistance mechanisms. Additionally, this review delves into the impact of epigenetic modifications, including DNA methylation and histone changes, on melanoma progression. The tumor microenvironment, characterized by immune cells, stromal cells, and soluble factors, plays a pivotal role in modulating tumor behavior and treatment responses. Emerging technologies like single-cell sequencing, CRISPR-Cas9, and AI-driven diagnostics are transforming melanoma research, offering precise and personalized approaches to treatment. Immunotherapy, particularly immune checkpoint inhibitors and personalized mRNA vaccines, has revolutionized melanoma therapy by enhancing the body's immune response. Despite these advances, resistance mechanisms remain a challenge, underscoring the need for combined therapies and ongoing research to achieve durable therapeutic responses. This comprehensive overview aims to highlight the current state of melanoma research and the transformative impacts of these advancements on clinical practice.

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis's role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Ferroptosis is a form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. Ferroptosis is currently proposed as one of the most promising means of combating tumor resistance. Nevertheless, the problem of ferroptosis resistance in certain cancer cells has been identified. This review first, investigates the mechanisms of ferroptosis induction in cancer cells. Next, the problem of cancer cell resistance to ferroptosis, as well as the underlying mechanisms is discussed. Recently discovered ferroptosis-suppressing biomarkers have been described. The various types of nanoparticles that can induce ferroptosis are also discussed. Given the ability of nanoparticles to combine multiple agents, this review proposes nanoparticle-based ferroptosis cell death as a viable method of circumventing this resistance. This review suggests combining ferroptosis with other forms of cell death, such as apoptosis, cuproptosis and autophagy. It also suggests combining ferroptosis with immunotherapy.

Anti-programmed death 1/programmed death ligand 1 (anti-PD-1/PD-L1) antibodies exert significant antitumor effects by overcoming tumor cell immune evasion and reversing T-cell exhaustion. However, the emergence of drug resistance causes most patients to respond poorly to these immune checkpoint inhibitors (ICIs). Studies have shown that insufficient T-cell infiltration, lack of PD-1 expression, deficient interferon signaling, loss of tumor antigen presentation, and abnormal lipid metabolism are all considered to be closely associated with immunotherapy resistance. To address drug resistance in tumor immunotherapy, a lot of research has concentrated on developing combination therapy strategies. Currently, ICIs such as anti-PD-1 /PD-L1 antibody combined with chemotherapy and targeted therapy have been approved for clinical treatment. In this review, we analyze the mechanisms of resistance to anti-PD-1/PD-L1 therapy in terms of the tumor microenvironment, gut microbiota, epigenetic regulation, and co-inhibitory immune checkpoint receptors. We also discuss various promising combination therapeutic strategies to address resistance to anti-PD-1/PD-L1 drugs, including combining these therapies with traditional Chinese medicine, non-coding RNAs, targeted therapy, other ICIs, and personalized cancer vaccines. Moreover, we focus on biomarkers that predict resistance to anti-PD-1/PD-L1 therapy as well as combination therapy efficacy. Finally, we suggest ways to further expand the application of immunotherapy through personalized combination strategies using biomarker systems.

As one of the earliest discovered lncRNA molecules, lncRNA H19 is usually expressed in large quantities during embryonic development and is involved in cell differentiation and tissue formation. In recent years, the role of lncRNA H19 in tumors has been gradually recognized. Increasing evidence suggests that its aberrant expression is closely related to cancer development. LncRNA H19 as an oncogene not only promotes the growth, proliferation, invasion and metastasis of many tumors, but also develops resistance to treatment, affecting patients' prognosis and survival. Therefore, in this review, we summarise the extensive research on the involvement of lncRNA H19 in tumor progression and discuss how lncRNA H19, as a key target gene, affects tumor sensitivity to radiotherapy, chemotherapy and immunotherapy by participating in multiple cellular processes and regulating multiple signaling pathways, which provides a promising prospect for further research into the treatment of cancer.

Malignant melanoma (MM) is a highly aggressive skin tumour.

To investigate whether miR-22 is involved in the proliferation, invasion, and migration of melanoma cells (MCs) by negatively regulating NOD-like receptor protein 3 (NLRP3) gene.

Human MCs (WM239a) and human epidermal melanocytes (HEM) were used as study material. The expression levels of miR-22 and NLRP3 were detected by qRT-PCR. The expression of NLRP3 protein was determined by Western blot (WB) analysis. The effects of miR-22 and NLRP3 on the proliferation, invasion, and migration of MCs were evaluated by cell counting kit-8 (CCK-8), Transwell cell invasion assay, and scratch assay.

The expression of miR-22 was clearly lower in WM239a than in HEM. Up-regulation of miR-22 expression in WM239a clearly raised the expression of miR-22, Caspase-1, and E-cadherin and the apoptotic rate of WM239a; however, the levels of interleukin-1β (IL-1β) and NLRP3, cell proliferation activity, invasion and migration ability were clearly decreased. The negative regulation of NLRP3 by miR-22 may play a major role in activities of MM.

Further studies will help to reveal the molecular details of this regulatory mechanism and provide new therapeutic strategies.

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.

Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis-miRNA-exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases.

In order to explore the therapeutic effect of Resveratrol (Res)-activated Natural Killer (NK) cells on canine mammary tumors, this study employed a range of assays, including wound healing, colony formation, Transwell, flow cytometry, and Western blot experiments, to investigate the impact of Res-pretreated NK cells on canine mammary tumor cells in vitro. Additionally, a tumor-bearing mouse model was utilized to further analyze the therapeutic effects of Res-pretreated NK cells in vivo. The results showed that Res enhances the capacity of NK cells to induce apoptosis, pyroptosis, and ferroptosis in canine breast tumor cells, while also augmenting their influence on the migration, invasion, and epithelial-mesenchymal transition of these cells. Furthermore, pretreatment of NK cells with Res significantly amplified their inhibitory effect on breast tumor growth in vivo and promoted tumor tissue apoptosis. Additionally, Res enhanced the recruitment of NK cells to other immune cells in the body. In summary, Res has been shown to enhance the anti-breast-tumor effect of NK cells both in vitro and in vivo, offering a new avenue for optimizing immunotherapy for canine breast tumors.