HMGB1 ubiquitination inhibition and extracellular secretion, mediated by m6A modified-exosomal lncRNA MALAT1, creates a communication between NK92-MI cells and tumor cells to aggravate acute lymphoblastic leukemia.

GALNT6-glycosylated LRG1 mediates the interaction between M2 macrophages and pancreatic cancer cells by activating CCR1/PI3K/AKT axis.

NOP2-regulated m5C Methylation of FKBP4 in Promoting Lung Adenocarcinoma Progression.

BACKGROUND Nucleolar protein 2 (NOP2), an RNA methyltransferase that mediates m5C modification, has been implicated in cancer progression; however, its specific role in lung adenocarcinoma (LUAD) remains unclear. This study investigated the functional significance of NOP2 and its regulation of FK506-binding protein 4 (FKBP4) in LUAD pathogenesis. MATERIALS AND METHODS The human normal alveolar epithelial cell line HPAEpiC and the LUAD cell lines A549 and H1975 were utilized in this study. In vivo experiments were conducted using male Sprague-Dawley rats. The functional roles of NOP2 and FKBP4 were explored by transfecting LUAD cells with overexpression vectors or small interfering RNAs (siRNAs). Quantitative real-time PCR, western blotting, immunofluorescence, and immunohistochemical staining analyses were used to evaluate NOP2 and FKBP4 expression in cells and tissues. Cell viability and proliferation were assessed using Cell Counting Kit-8 assays and 5-ethynyl-2'-deoxyuridine (EdU) staining. Apoptosis was measured by flow cytometry and TUNEL staining. Transwell assays were conducted to determine cell migration and invasion. Co-immunoprecipitation and RNA pulldown assays were conducted to characterize the interaction between NOP2 and FKBP4. RESULTS Analysis of data from The Cancer Genome Atlas (TCGA) database revealed that elevated expression of NOP2 and FKBP4 correlated with poor prognosis in patients with LUAD. Both NOP2 and FKBP4 were significantly upregulated in LUAD cell lines compared to normal controls. Knockdown of NOP2 could inhibit LUAD cell proliferation, migration, and invasion, and enhance apoptosis. In vivo experiments confirmed that NOP2 depletion inhibited tumor growth and enhanced apoptosis. Mechanistically, NOP2 could directly bind to FKBP4 and regulate its expression. Importantly, FKBP4 knockdown reversed the oncogenic effects of NOP2 expression, establishing FKBP4 as a critical downstream effector of NOP2 in LUAD. CONCLUSION Our study demonstrates that NOP2 promotes LUAD progression by regulating FKBP4 expression, potentially through m5C methylation, thereby highlighting the NOP2/FKBP4 axis as a potential therapeutic target. Overall, these findings provide new insights into the epigenetic mechanisms driving LUAD aggressiveness.

YBX1-mediated m5C modification of exosomal LGALS3 derived from M2 tumor-associated macrophages drives colorectal cancer cell malignant behaviors.

NSUN2 regulates PARP9 progression through m5C modification to mediate breast cancer progression.

BACKGROUND m5C modification plays a vital role in the progression of human cancers, including breast cancer (BC), but the function of NOP2/Sun RNA methyltransferase 2 (NSUN2), an RNA m5C modification enzyme, remains largely unclear. METHODS qRT-PCR, western blot and IHC assays were carried out to determine the expression of NSUN2, poly (ADP-ribose) polymerase 1 (PARP9) and Y box binding protein 1 (YBX1). EdU, flow cytometry, transwell, tube formation and sphere formation assays were conducted to evaluate cell proliferation, apoptosis, invasion, angiogenesis and stemness, respectively. ELISA was performed to examine the concentrations of inflammatory factors. RIP and pull-down assays were used to verify the interaction between NSUN2/YBX1 and PARP9. Murine xenograft model was constructed to explore the functions of NSUN2 and PARP9 in tumor growth in vivo. RESULTS PARP9 silencing suppressed the proliferation, invasion, angiogenesis, stemness and immune escape, and promoted apoptosis in BC cells in vitro. Mechanically, NSUN2 functioned as an m5C writer that catalyzed m5C modification of PARP9 mRNA, while YBX1 acted as an m5C reader that recognized the modified transcript and enhanced its stability, thereby elevating PARP9 expression in BC cells. YBX1 could elevate PARP9 expression in BC cells. Moreover, NSUN2 knockdown restrained the malignant behaviors of BC cells, with PARP9 overexpression restored the effects. In addition, NSUN2 knockdown blocked tumorigenesis in vivo by regulating PARP9 expression. CONCLUSION NSUN2-mediated m5C modification stabilizes PARP9 mRNA and is associated with enhanced BC progression and immune escape. The results broadened our understanding of the pathogenic mechanism of BC.

LncRNA OTUD6B-AS1 overexpression induces parthanatos in esophageal adenocarcinoma cells by binding to miR-145-5p and promoting AIF expression.

OtUD6B-AS1 suppresses EAC progression by sponging miR-145-5p and upregulating AIF to induce parthanatos activation, and Targeting this ceRNA regulatory axis may be a therapeutic strategy for EAC.

Integrated Transcriptomic and Functional Profiling Reveals IL-7R/FOXO1 Axis as a Target of Momordicine I in Meningioma.

INTRODUCTION Meningiomas are common intracranial tumors lacking effective chemotherapeutic options. Momordicine I, a triterpenoid isolated from bitter melon, has demonstrated anticancer activity, but its effects on meningioma remain unclear. The effect of Momordicine I on meningiomas is studied in this research. METHODS Human meningioma cells (IOMM-Lee and patient-derived P9) were treated with momordicine I. Cell viability, colony formation, migration, apoptosis, and cell cycle progression were assessed. RNA sequencing, qRT-PCR, Western blotting, and Seahorse analysis were used to investigate molecular mechanisms. RESULTS Momordicine I inhibited cell proliferation, colony formation, and migration, while inducing apoptosis and G1/G2-M phase arrest. Transcriptomic analysis revealed downregulation of IL7R, FOXO1, and PLK2. Treatment also increased γ-H2AX and reduced Survivin and Bcl-xL expression, indicating apoptosis via DNA damage and survival signaling suppression. Furthermore, mitochondrial oxidative phosphorylation was impaired. DISCUSSION These findings suggest that Momordicine I exerts its antitumor activity through coordinated suppression of cell survival pathways, modulation of cell cycle regulators, and mitochondrial dysfunction. Downregulation of IL7R and FOXO1, both associated with tumor progression and survival, underscores the potential of Momordicine I as a multi-pathway therapeutic agent. CONCLUSION Momordicine I demonstrates potent anti-meningioma effects by targeting the IL7R/FOXO1 axis, inducing apoptosis, and impairing mitochondrial metabolism. These results support its development as a novel therapeutic candidate for malignant meningioma treatment.