Search Results (48)

This review delves into the characteristics of lipid metabolism reprogramming in cancer cells and immune cells within the tumor microenvironment (TME), discussing its role in tumorigenesis and development and analyzing the value of lipid metabolism-related molecules in tumor diagnosis and prognosis. Cancer cells support their rapid growth through aerobic glycolysis and lipid metabolism reprogramming. Lipid metabolism plays distinct roles in cancer and immune cells, including energy supply, cell proliferation, angiogenesis, immune suppression, and tumor metastasis. This review focused on shared lipid metabolic enzymes and transporters, lipid metabolism-related oncogenes and non-coding RNAs (ncRNAs) involved in cancer cells, and the influence of lipid metabolism on T cells, dendritic cells (DCs), B cells, tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), and natural killer cells (NKs) within TME. Additionally, the role of lipid metabolism in tumor diagnosis and prognosis was explored, and lipid metabolism-based anti-tumor treatment strategies were summarized, aiming to provide new perspectives for achieving precision medicine. Full article

Disruption of the gut microenvironment is a hallmark of HIV infection, where regulatory T cells (Tregs) play a critical role in maintaining gut homeostasis. However, the mechanisms by which gut Tregs contribute to immune reconstitution failure in HIV-infected individuals remain poorly understood. In this study, we employed single-cell RNA sequencing (scRNA-seq) to analyze gut Treg populations across three cohorts: eight immunological responders (IRs), three immunological non-responders (INRs), and four HIV-negative controls (NCs). Our findings revealed that INRs exhibit an increased proportion of gut Tregs but with significant functional impairments, including reduced suppressive capacity and heightened apoptotic activity. Notably, these Tregs underwent metabolic reprogramming in INRs, marked by an upregulation of glycolysis-related genes and a downregulation of the oxidative phosphorylation (OXPHOS) pathway. Additionally, both the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA concentrations were reduced in INRs. In vitro SCFA supplementation restored Treg function by enhancing suppressive capacity, reducing early apoptosis, and rebalancing cellular energy metabolism from glycolysis to OXPHOS. These findings provide a comprehensive characterization of gut Treg dysfunction in INRs and underscore the therapeutic potential of targeting gut Tregs through microbiota and metabolite supplementation to improve immune reconstitution in HIV-infected individuals. Full article

Ferroptosis is a type of cell death executed by phospholipid peroxidation in an iron-dependent manner. Ferroptosis plays a central role in inhibiting tumor growth, enhancing the immune response, and is now considered a strategy to combat resistance to anticancer therapies. The oncosuppressor p53 is one of the major regulators of ferroptosis and can either promote or inhibit ferroptosis, depending on the context and/or extent of the damage. p53 governs the transcription of many genes that modulate cell susceptibility to ferroptosis, using this manner of death to fulfill its role as tumor suppressor. The diverse functions of p53 are related to non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), since they can either regulate p53 or be regulated by p53. Therefore, an intricate metabolic network between ncRNAs and p53 ensures the correct response. In this review, we will discuss recent studies on the molecular interplay between p53-mediated ferroptosis and ncRNAs and how this contributes directly or indirectly to the outcome of ferroptosis. Full article

Background: Deficiency of IL-36 Receptor Antagonist (DITRA) is a rare monogenic autoinflammatory disease, characterized by dysregulation of IL-36 signaling and phenotypically classified as a subtype of generalized pustular psoriasis. Objectives: This study aimed to explore the role of potentially coding and non-coding RNAs (ncRNAs) in the IL36RN interactome to identify putative pathogenic mechanisms, biomarkers, and therapeutic targets for DITRA. Methods: A systems biology approach was applied using the STRING database to construct the IL36RN protein–protein interaction network. Key ncRNA interactions were identified using RNAInter. The networks were visualized and analyzed with Cytoscape v3 and the CytoHubba plugin to identify central nodes and interaction hubs. Pathway enrichment analysis was then performed to determine the biological relevance of candidate ncRNAs and genes. Results: Analysis identified thirty-eight ncRNAs interacting with the IL36RN network, including six lncRNAs and thirty-two miRNAs. Of these, thirty-three were associated with key DITRA-related signaling pathways, while five remain to be validated. Additionally, seven protein-coding genes were highlighted, with three (TINCR, PLEKHA1, and HNF4A) directly implicated in biological pathways related to DITRA. Many of the identified ncRNAs have prior associations with immune-mediated diseases, including psoriasis, supporting their potential relevance in DITRA pathogenesis. Conclusions: This study provides novel insights into the ncRNA-mediated regulation of IL36RN and its network in the context of DITRA. The findings support the potential utility of specific ncRNAs and genes, such as TINCR, PLEKHA1, and HNF4A, as key genomic elements warrant further functional characterization to confirm their mechanistic roles and may inform biomarker discovery and targeted therapeutic development in DITRA. Full article

Introduction: Anal squamous cell carcinoma (ASCC) is a rare but increasingly common gastrointestinal malignancy, mainly associated with oncogenic human papillomaviruses (HPVs). The role of non-coding RNAs (ncRNAs) in tumorigenesis is recognized, but the impact of viral ncRNAs on host gene expression remains unclear. Methods: We re-analyzed total RNA-Seq data from 70 anal biopsies: 31 low-grade squamous intraepithelial lesions (LGSIL), 16 high-grade SIL (HGSIL), and 23 ASCC cases. Microbial composition was assessed taxonomically. Novel viral miRNAs were predicted using vsRNAfinder and linked to host targets using TargetScan and expression correlation analyses. Results: Microbial profiling revealed significant differences in abundance, with Alphapapillomaviruses types 9, 10, and 14 enriched across lesion grades. We identified 90 novel viral miRNAs and 177 significant anti-correlated miRNA–mRNA interactions. Target genes were enriched in pathways related to cell cycle, epithelial–mesenchymal transition, lipid metabolism, immune modulation, and viral replication. Discussion: Our findings suggest that HPV-derived miRNAs, including those from low-risk types, may contribute to neoplastic transformation by modulating host regulatory networks. Conclusion: This study highlights viral miRNAs as potential drivers of HPV-related anal cancer and supports their utility as early biomarkers and therapeutic targets in ASCC. Full article

Exosomes are nanoscale vesicles secreted by cells that play vital regulatory roles in intercellular communication and immune responses. Listeria monocytogenes (L. Monocytogenes, LM) is a notable Gram-positive intracellular parasitic bacterium that infects humans and diverse animal species. However, the specific biological function of exosomes secreted by macrophages during L. Monocytogenes infection (hereafter EXO-LM) remains elusive. Here, we discovered that EXO-LM stimulated the secretion of inflammation-associated cytokines by macrophages, facilitating the intracellular survival of L. monocytogenes within macrophages. Transcriptomic analysis shows that EXO-LM significantly upregulates immune recognition and inflammation-related signaling pathways in macrophages. Furthermore, a ceRNA regulatory network comprising exosomal ncRNAs and macrophage RNAs was constructed through EXO-LM transcriptome sequencing. Utilizing bioinformatics and dual-luciferase reporter assays, we identified two potential binding sites between lncRNA Rpl13a-213 and miR-132-3p. Cell transfection experiments demonstrated that Rpl13a-213 overexpression augmented pro-inflammatory cytokine expression in macrophages, in contrast to the suppression by miR-132-3p overexpression. The decrease in Rpl13a-213 upon EXO-LM stimulation enhances miR-132-3p expression, dampening the inflammatory response in macrophages and aiding L. monocytogenes intracellular survival. This study unveils the immunomodulatory function of exosomal ncRNAs originating from macrophages, which provides fresh perspectives into the mechanisms underlying macrophage inflammatory response regulation by L. monocytogenes-infected cell-derived exosomes. Full article

Leukemia is a heterogeneous group of hematological malignancies. Despite the enormous progress that has been made in the field of hemato-oncology in recent years, there are still many problems related to, among others, disease recurrence and drug resistance, which is why the search for ideal biomarkers with high clinical utility continues. Research shows that exosomes play a critical role in the biology of leukemia and are associated with the drug resistance, metastasis, and immune status of leukemias. Exosomes with their cargo of non-coding RNAs act as a kind of intermediary in intercellular communication and, at the same time, have the ability to manipulate the cell microenvironment and influence the reaction, proliferative, angiogenic, and migratory properties of cells. Exosomal ncRNAs (in particular, circRNAs and microRNAs) appear to be promising cell-free biomarkers for diagnostic, prognostic, and treatment monitoring of leukemias. This review examines the expression of exosomal ncRNAs in leukemias and their potential regulatory role in leukemia therapy but also in conditions such as disease relapse, drug resistance, metastasis, and immune status. Given the key role of ncRNAs in regulating gene networks and intracellular pathways through their ability to interact with DNA, transcripts, and proteins and identifying their specific target genes, defining potential functions and therapeutic strategies will provide valuable information. Full article

Recurrent Pregnancy Loss (RPL), also named Recurrent Spontaneous Abortion (RSA), is a common fertility problem that refers to at least two consecutive pregnancy losses and affects 1–2% of couples all over the world. Despite common causes such as genetic abnormalities, uterine anomalies or hormonal and metabolic disorders, there is still a huge challenge in identifying the causes of about 40–60% of RPL patients. Circular RNAs (circRNAs) are endogenous ncRNAs with a unique closed-loop and single-stranded structure. Accumulated evidence indicates the role of circRNAs in embryonic development and implantation, which may help decipher the mechanisms and causes underlying RSA. Four works were selected in the SRA public repository that used RNAseq analysis in control and RPL samples in four tissues: endometrium, chorionic villus tissue, decidua and decidua immune cells. Two programs were selected for circRNA detection: DCC and CIRI2. A total of 1715 candidate circRNAs were detected after filtering the results. In the differential expression analysis, decidual tissue showed the highest percentage of circRNA with differential expression between cases and controls. CircRNAs originating from genes OGA, FNDC3B, RAB11FIP1, SIPA1L2 and GREB1L showed the highest expression in women suffering from pregnancy losses, in decidual tissue or endometrium. In the GO term enrichment analysis, multiple terms related to embryonic development and immunological response were consistently enriched in villus and decidual tissues. Although some differentially expressed circRNAs were shared between tissues, decidua seems the tissue of choice for analyzing the role of circRNAs in RPL. Full article

Non-coding RNAs (ncRNAs) and the innate immune system are closely related, acting as defense mechanisms and regulating gene expression and innate immunity. Both are modulators in the initiation, development and progression of cancer. We aimed to review the major types of ncRNAs, including small interfering RNAs (siRNAs), microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and long non-coding RNAs (lncRNAs), with a focus on cancer, innate immunity, and inflammation. We found that ncRNAs are closely related to innate immunity, epigenetics, chronic inflammation, and cancer and share properties such as inducibility, specificity, memory, and transfer. These similarities and interrelationships suggest that ncRNAs and modulators of trained immunity, together with the control of chronic inflammation, can be combined to develop novel therapeutic approaches for personalized cancer treatment. In conclusion, the close relationship between ncRNAs, the innate immune system, and inflammation highlights their importance in cancer pathways and their potential as targets for novel therapeutic strategies. Full article

Ovarian cancer (OC), known for its lethality and resistance to chemotherapy, is closely associated with iron metabolism and ferroptosis—an iron-dependent cell death process, distinct from both autophagy and apoptosis. Emerging evidence suggests that dysregulation of iron metabolism could play a crucial role in OC by inducing an imbalance in the redox system, which leads to ferroptosis, offering a novel therapeutic approach. This review examines how disruptions in iron metabolism, which affect redox balance, impact OC progression, focusing on its essential cellular functions and potential as a therapeutic target. It highlights the molecular interplay, including the role of non-coding RNAs (ncRNAs), between iron metabolism and ferroptosis, and explores their interactions with key immune cells such as macrophages and T cells, as well as inflammation within the tumor microenvironment. The review also discusses how glycolysis-related iron metabolism influences ferroptosis via reactive oxygen species. Targeting these pathways, especially through agents that modulate iron metabolism and ferroptosis, presents promising therapeutic prospects. The review emphasizes the need for deeper insights into iron metabolism and ferroptosis within the redox-regulated system to enhance OC therapy and advocates for continued research into these mechanisms as potential strategies to combat OC. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various biomolecule cargoes, such as lipids, proteins, and nucleic acids. EVs are released from nearly all types of cells and have been shown to play an important role in cell-to-cell communication. In recent years, many studies have investigated the role of EVs in cancer, including HCC. Emerging studies have shown that EVs play primary roles in the development and progression of cancer, modulating tumor growth and metastasis formation. Moreover, it has been observed that non-coding RNAs (ncRNAs) carried by tumor cell-derived EVs promote tumorigenesis, regulating the tumor microenvironment (TME) and playing critical roles in the progression, angiogenesis, metastasis, immune escape, and drug resistance of HCC. EV-related ncRNAs can provide information regarding disease status, thus encompassing a role as biomarkers. In this review, we discuss the main roles of ncRNAs present in HCC-derived EVs, including micro(mi) RNAs, long non-coding (lnc) RNAs, and circular (circ) RNAs, and their potential clinical value as biomarkers and therapeutic targets. Full article

Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC₅₀ of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC. Full article

Multiple sclerosis (MS) is a degenerative condition characterized by axonal damage and demyelination induced by autoreactive immune cells that occur in the Central Nervous System (CNS). The interaction between epigenetic changes and genetic factors can be widely involved in the onset, development, and progression of the disease. Although numerous efforts were made to discover new therapies able to prevent and improve the course of MS, definitive curative treatments have not been found yet. However, in recent years, it has been reported that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), acting as gene expression regulators, could be used as potential therapeutic targets or biomarkers to diagnose and fight MS. In this review, we discussed the role of miRNAs, lncRNAs, and circRNAs, as well as their expression level changes and signaling pathways that are related to preclinical and human MS studies. Hence, the investigation of ncRNAs could be important to provide additional information regarding MS pathogenesis as well as promote the discovery of new therapeutic strategies or biomarkers. Full article

Exosomes have the ability to transport RNA/miRNAs and possess immune modulatory functions. Heat stress, a significant limiting factor in the poultry industry, can induce oxidative stress and suppress the immune responses of laying hens. In this study, we investigated the expression profiles of serum exosomes and their miRNAs in Roman laying hens who were fed a diet with either 0 or 200 mg/kg curcumin under heat stress conditions. The numbers of exosomes were significantly higher in both the HC (heat stress) and HT (heat stress with 200 mg/kg curcumin) groups compared to the NC (control) group and NT (control with 200 mg/kg curcumin) group (p < 0.05). Additionally, we observed that the most prevalent particle diameters were 68.75 nm, 68.25 nm, 54.25 nm, and 60.25 nm in the NC, NT, HC, and HT groups, respectively. From our sRNA library analysis, we identified a total of 863 unique miRNAs; among them, we screened out for subsequent bioinformatics analysis a total of 328 gga-miRNAs(chicken miRNA from the miRbase database). The KEGG pathways that are associated with target genes which are regulated by differentially expressed miRNAs across all four groups at a p-value < 0.01 included oxidative phosphorylation, protein export, cysteine and methionine metabolism, fatty acid degradation, ubiquitin-mediated proteolysis, and cardiac muscle contraction. The above findings suggest that curcumin could mitigate heat-induced effects on laying hens by altering the miRNA expression profiles of serum exosomes along with related regulatory pathways. Full article

Noncoding RNAs (ncRNAs) constitute a class of RNA molecules that lack protein-coding capacity. ncRNAs frequently modulate gene expression through specific interactions with target proteins or messenger RNAs, thereby playing integral roles in a wide array of cellular processes. The Flavivirus genus comprises several significant members, such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV), which have caused global outbreaks, resulting in high morbidity and mortality in human populations. The life cycle of arthropod-borne flaviviruses encompasses their transmission between hematophagous insect vectors and mammalian hosts. During this process, a complex three-way interplay occurs among the pathogen, vector, and host, with ncRNAs exerting a critical regulatory influence. ncRNAs not only constitute a crucial regulatory mechanism that has emerged from the coevolution of viruses and their hosts but also hold potential as antiviral targets for controlling flavivirus epidemics. This review introduces the biogenesis of flavivirus-derived ncRNAs and summarizes the regulatory roles of ncRNAs in viral replication, vector-mediated viral transmission, antiviral innate immunity, and viral pathogenicity. A profound comprehension of the interplay between ncRNAs and flaviviruses will help formulate efficacious prophylactic and therapeutic strategies against flavivirus-related diseases. Full article