Background/Objectives: EBV is an oncogenic virus linked to NPC and GC, driving cisplatin resistance. Resveratrol has anticancer activity, but its targets and mechanisms against EBV-positive cancers remain unclear. Methods: We assessed resveratrol’s cytotoxicity in EBV-positive cells via functional assays, identified targets by chemical similarity search and molecular docking, and validated PTPN1 via in vitro experiments and nude mouse xenograft models. Results: Resveratrol inhibited EBV-positive cell viability in a time- and concentration- dependent manner, with IC50 values ranging from 35.85 to 145.7 μM across different cell lines at 24–72 h. Apoptosis rates increased by approximately 2- to 4-fold after 80 μM resveratrol treatment for 24 h. Resveratrol directly targeted PTPN1 (docking score = −4.89) and promoted its degradation via the proteasome pathway, as MG132 reversed this effect. Notably, resveratrol synergized with cisplatin (combination index < 1) to reverse cisplatin resistance in both in vitro and in vivo models. Furthermore, resveratrol induced EBV lytic reactivation through ROS production, as evidenced by the increased expression of BZLF1, BMRF1, and BALF2, which was attenuated by the ROS scavenger NAC. Conclusions: Our findings identify PTPN1 as a direct anticancer target of resveratrol in EBV-positive cancers. Resveratrol enhances the therapeutic efficacy of cisplatin via PTPN1 proteasomal degradation and induces EBV lytic reactivation through ROS accumulation. These findings provide a mechanistic basis for the development of novel combination therapies targeting EBV-associated malignancies.

Nasopharyngeal carcinoma (NPC) represents an Epstein-Barr virus (EBV)-associated malignancy showing elevated incidence in East and Southeast Asia. Early detection remains vital, as molecular abnormalities precede visible histological changes during tumor development. This review summarizes recent progress in decoding NPC's molecular profile, including genetic mutations, epigenetic alterations, non-coding RNA networks and proteomic alterations. Importantly, these molecular discoveries are increasingly informing clinical approaches to disease management. Modern diagnostic integration of histopathology, EBV biomarkers and advanced imaging has improved detection, yet locoregional recurrence and distant metastasis remain major causes of mortality. Immunotherapy shows promising efficacy in recurrent/metastatic NPC, underscoring the potential of molecular insights to guide therapeutic innovation.

EBV employs multiple strategies to subvert host innate immunity, including suppression of type I IFN signaling. However, the precise mechanism by which its latent oncoprotein LMP1 modulates this pathway in nasopharyngeal carcinoma (NPC) remains unclear. Here, we demonstrated that LMP1 enhances the interaction between interferon regulatory factor 3 (IRF3) and E3 ubiquitin ligase Ro52, which leads to the degradation of IRF3 protein. Low IRF3 expression correlates with poor prognosis in NPC patients. Notably, IRF3 may inhibit cell G1/S transition by directly inducing CDKN2C transcription, which suggests the direct effect as a moonlighting protein in regulating cell cycle. Cisplatin is an effective DNA-damaging anti-tumor agent which may activate type I IFNs-mediated anti-tumor immunity by stimulating the release of dsDNA. EBV (LMP1) inhibits cisplatin-activated type I IFN signaling by reducing IRF3 expression. The activation of IRF3 enhances the sensitivity of EBV (LMP1)-positive NPC cells to cisplatin in vitro and in vivo. These findings establish the LMP1-Ro52-IRF3 axis as a critical immune evasion mechanism that drives cisplatin resistance and suggest that targeting this axis represents a viable strategy to enhance chemotherapy efficacy in EBV-positive NPC.

Epstein-Barr virus (EBV) is a key oncogenic driver of nasopharyngeal carcinoma (NPC) and is closely associated with cisplatin resistance, but its roles in metabolic reprogramming and chemoresistance remain unclear. This study aimed to investigate the role of EBV in polyamine metabolic reprogramming and its underlying mechanism in mediating cisplatin resistance in NPC. Metabolomic and Metabolic Flux Analysis confirmed that EBV significantly enhances polyamine anabolism in NPC cells, with ODC1, the rate-limiting enzyme of polyamine biosynthesis, transcriptionally upregulated by EBV-BZLF1 via direct binding to its promoter. Functional experiments revealed that the ODC1-spermidine axis promotes EBV replication and cell proliferation via eIF5A hypusination by upregulating EBV-EAD and host TRAF1, respectively, and induces B-to-Z DNA transition to attenuate cGAS-STING-mediated innate immune responses. Clinically, high ODC1 expression was an independent prognostic marker for poor survival in NPC patients. In vitro and in vivo, ODC1 knockdown or pharmacological inhibition with DFMO effectively restored cisplatin sensitivity in EBV-positive NPC cells, likely by reducing Z-DNA formation and potentiating cisplatin-induced innate immune responses. Collectively, our findings identify a novel EBV-ODC1-polyamine regulatory axis that promotes viral replication and confers a survival advantage to cancer cells, highlighting ODC1 as a promising therapeutic target to improve cisplatin efficacy in EBV-positive NPC.

Cancer continues to pose a significant threat to global health, with its status as a leading cause of death remaining unchallenged. Within the realm of cancer research, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stands out as a critical player, having been identified in the 1990s as the tenth member of the TNF family. This review examines the pivotal role of TRAIL in cancer biology, focusing on its ability to induce apoptosis in malignant cells through both endogenous and exogenous pathways. We provide an in-depth analysis of TRAIL’s intracellular signaling and intercellular communication, underscoring its potential as a selective anticancer agent. Additionally, the review explores TRAIL’s capacity to reshape the tumor microenvironment, thereby influencing cancer progression and response to therapy. With an eye towards future developments, we discuss the prospects of harnessing TRAIL’s capabilities for the creation of tailored, precision-based cancer treatments, aiming to enhance efficacy and improve patient survival rates.

Ferroptosis is a novel and iron-dependent form of programmed cell death, which has been implicated in the pathogenesis of various human cancers. EBV is a well-recognized oncogenic virus that controls multiple signaling pathways within the host cell, including ferroptosis signaling. Recent studies show that inducing ferroptosis could be an efficient therapeutic strategy for EBV-associated tumors. This review will firstly describe the mechanism of ferroptosis, then summarize EBV infection and EBV-associated tumors, as well as the crosstalk between EBV infection and the ferroptosis signaling pathway, and finally discuss the role and potential application of ferroptosis-related reagents in EBV-associated tumors.

Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, alpha-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.

Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality rates, and is often accompanied by distant metastases. Metastasis is a major cause of shortened survival time and poor treatment outcomes for patients with CRC. However, the molecular mechanisms underlying the metastasis of CRC remain unclear. Exosomes are a class of small extracellular vesicles that originate from almost all human cells and can transmit biological information (e.g., nucleic acids, lipids, proteins, and metabolites) from secretory cells to target recipient cells. Recent studies have revealed that non-coding RNAs (ncRNAs) can be released by exosomes into the tumour microenvironment or specific tissues, and play a pivotal role in tumorigenesis by regulating a series of key molecules or signalling pathways, particularly those involved in tumour metastasis. Exosomal ncRNAs have potential as novel therapeutic targets for CRC metastasis, and can also be used as liquid biopsy biomarkers because of their specificity and sensitivity. Therefore, further investigations into the biological function and clinical value of exosomal ncRNAs will be of great value for the prevention, early diagnosis, and treatment of CRC metastasis.

As a free radical and endogenous effector molecule, mammalian endogenous nitric oxide (NO) is mainly derived from nitric oxide synthase (NOS) via L-arginine. NO participates in normal physiological reactions and provides immune responses to prevent the invasion of foreign bacteria. However, NO also has complex and contradictory biological effects. Abnormal NO signaling is involved in the progression of many diseases, such as cancer. In the past decades, cancer research has been closely linked with NOS/ NO, and many tumors with poor prognosis are associated with high expression of NOS. In this review, we give a overview of the biological effects of NOS/ NO. Then we focus on the oncogenic role of iNOS/ NO in HPV, HBV, EBV and H. pylori related tumors. In fact, there is growing evidence that iNOS could be used as a potential therapeutic target in cancer therapy. We emphasize that the pro-tumor effect of NOS/ NO is greater than the anti-tumor effect.

High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1(+)) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1(+) and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1(+) in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

Cervical cancer is one of the most common types of cancer and the fourth leading cause of cancer‑related deaths in women. The occurrence and development of cervical cancer is a multifactorial and multilevel process, which usually occurs alongside a continuous high‑risk human papillomavirus infection. With further developments in molecular biology and the advancement of sequencing technology, the role of biomarkers in cervical diseases has been gradually recognized. Therefore, it remains a priority to identify key molecular markers that can be used for the screening and triaging of the lesions. In recent years, numerous studies have been conducted in order to identify important markers for cervical diseases. The present review aimed to summarize the molecular alterations and clinical relevance of chromosomal alterations, DNA polymorphisms, the DNA methylation status, histone modifications, and alterations in microRNA and protein expression levels. Accumulating evidence suggests that molecular alterations may reflect the degree and the prognosis of the disease. Although significant progress has been made in the field of cervical cancer research, further samples and experiments are still required to identify crucial molecules.

EBV infection is a recognized epigenetic driver of carcinogenesis. We previously showed that EBV could protect cancer cells from TNF-induced necroptosis. This study aims to explore the epigenetic mechanisms allowing cancer cells with EBV infection to escape from RIP3-dependent necroptosis. Methods: Data from the TCGA database were used to evaluate the prognostic value of RIP3 promoter methylation and its expression. Western blotting, real-time PCR, and immunochemistry were conducted to investigate the relationship between LMP1 and RIP3 in cell lines and NPC tissues. BSP, MSP and hMeDIP assays were used to examine the methylation level. Induction of necroptosis was detected by cell viability assay, p-MLKL, and Sytox Green staining. Results: RIP3 promoter hypermethylation is an independent prognostic factor of poorer disease-free and overall survival in HNSCC patients, respectively. RIP3 is down-regulated in NPC (a subtype of HNSCC). EBV(LMP1) suppresses RIP3 expression by hypermethylation of the RIP3 promoter. RIP3 protein expression was inversely correlated with LMP1 expression in NPC tissues. Restoring RIP3 expression in EBV(LMP1)-positive cells inhibits xenograft tumor growth. The accumulation of fumarate and reduction of α-KG in EBV(LMP1)-positive cells led to RIP3 silencing due to the inactivation of TETs. Decreased FH activity caused fumarate accumulation, which might be associated with its acetylation. Incubating cells with fumarate protected NPC cells from TNF-induced necroptosis. Conclusion: These results demonstrate a pathway by which EBV(LMP1)-associated metabolite changes inhibited necroptosis signaling by DNA methylation, and shed light on the mechanism underlying EBV-related carcinogenesis, which may provide new options for cancer diagnosis and therapy.

Intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPCs) are vascular tumors that have a high rate of local recurrence and extracranial metastases. Intradural extramedullary spinal dissemination of intracranial SFT/HPC is extremely rare. There is a paucity of data available to elucidate the molecular mechanisms of intraspinal dissemination of intracranial SFT/HPC. Herein, we presented a case of intracranial SFT/HPC with intraspinal metastasis. The resected tumor specimens were enrolled in a clinical sequencing program, including whole-exome and transcriptome sequencing. By comparing genomic sequencing data of the intracranial tumors with intraspinal metastasis, we established the somatic mutational profiles of these tumors. Clonality analysis revealed a distinct subclonal structure in the intracranial tumor and its intraspinal metastasis, which might reflect the possibility of intratumoral clonal selection and evolution during the process of tumor dissemination. Through bioinformatics analysis and Sanger sequencing validation, a DSTYK mutation (Met296Ile) was identified as a candidate driver of intraspinal metastasis in this SFT/HPC case. Further, an intracranial tumor-derived SFT/HPC cell line, HPC3, was established to explore the mechanisms of the DSTYK mutation in promoting SFT/HPC metastasis. Based on the HPC3 cell model, we found that the DSTYK mutation promoted cell migration and invasion of HPC3 cells via activation of ERK1/2 signaling, which was inhibited by the MEK/ERK inhibitor AZD6244. The DSTYK mutation was also shown to upregulate the expression of two metastasis-related molecules: MMP2 and MMP9 in HPC3 cells; however, this effect was attenuated by AZD6244 treatment. Therefore, the DSTYK mutation may activate ERK1/2/MMP2/9 signaling to promote tumor cell metastasis in SFT/HPC. In conclusion, our study revealed the potential role of DSTYK mutation in the regulation of intraspinal metastasis of SFT/HPC, which might provide new biological insights into this rare disease.