eIF3A Promotes the Warburg Effect in Cervical Cancer through m6A-dependent Translational Regulation of ENO1.

eIF4A1 enhances p70S6K mRNA translation and promotes nuclear β-catenin levels to augment stemness and metastasis in gastric cancer cells.

Gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide, with tumor stemness and metastasis driving poor prognosis. This study explores the role of eukaryotic translation initiation factor 4A1 (eIF4A1) in promoting these aggressive features in GC. eIF4A1 was found to be upregulated in stem-like (CD133+) GC cells. Gain- and loss-of-function experiments in cell lines, combined with xenograft, chemically induced, and organoid models, demonstrated that eIF4A1 enhanced cancer stemness, cell mobility, tumorigenesis, and metastasis. Mechanistically, eIF4A1 selectively promotes p70 ribosomal S6 kinase (p70S6K) mRNA translation, leading to increased glycogen synthase kinase 3 beta (GSK3β) phosphorylation, elevated nuclear β-catenin accumulation, and subsequent transcriptional activation of eIF4A1 via the β-catenin/transcription factor 7-like 2 (TCF7L2) complex, thus forming a positive feedback loop. Clinically, high expression of eIF4A1, p70S6K, and TCF7L2 correlates with unfavorable prognosis in GC patients. These findings highlight eIF4A1 as a key regulator of stemness and metastasis through a novel translational feedback mechanism, suggesting potential therapeutic targeting to disrupt tumor progression.

piR-164552 promotes malignant progression in head and neck squamous cell carcinoma via the RBM4/EIF4E2 signaling axis: Insights from multi-omics and functional analyses

Integrated transcriptomic and translatomic profiling demonstrated that this axis orchestrated extensive reprogramming of mRNA metabolism, ribosome biogenesis and cancer-associated signaling pathways, underscoring its multilayered role in tumor progression.

NAT10 promotes prostate cancer progression by acetylating mRNA of MARK2 and activating mTOR/HIF-1α/C-Myc pathway to enhance glycolytic reprogramming.

MYC-driven BYSL overexpression promotes hepatocellular carcinoma by suppressing nucleolar stress and inactivating the RPL5/RPL11-MDM2-p53 pathway.

BYSL gene encodes the bystin-like (BYSL) protein, a nucleolar protein involved in eukaryotic ribosome biogenesis and essential for 40S ribosomal subunit synthesis. Although BYSL upregulation has been implicated in hepatocellular carcinoma, its mechanistic contribution to tumor progression remains undefined. We observed that BYSL is consistently upregulated across multiple cancer types and is associated with adverse clinicopathological features and poor prognosis, with the strongest clinical relevance observed in hepatocellular carcinoma through the integrative transcriptomic and proteomic analyses. BYSL-knockout suppresses malignant phenotypes, including proliferation, migration, and invasion, and induced G1/S arrest and apoptosis. Mechanistically, loss of BYSL disrupts nucleolar homeostasis and reduces global protein synthesis, thereby activating the RPL5/RPL11-MDM2-p53 axis, leading to p53 stabilization and tumor suppression. Importantly, MYC directly bound to the BYSL promoter and transcriptionally activated its expression, whereas co-targeting BYSL and MYC produced more synergistic antitumor effects than either intervention alone. Collectively, our study reveals that BYSL acts as a pivotal downstream mediator of MYC-regulated ribosome biogenesis and promotes hepatocellular carcinoma progression. Our findings suggest that BYSL may represent a potential therapeutic target for hepatocellular carcinoma; nevertheless, additional in vivo preclinical studies are warranted to validate its translational prospects.

Dual relevance of EIF2S1 in acute myeloid leukemia: linking poor prognosis to immune-metabolic states and leukemic cell fitness

Background Most transcriptomic studies in acute myeloid leukemia (AML) have focused on transcriptional regulation, whereas the clinical and biological relevance of translation initiation factors remains insufficiently defined. Eukaryotic translation initiation factor 2 subunit alpha (EIF2S1) is a key regulator of translation initiation, but its prognostic significance and association with AML remain unclear. Methods Bulk RNA-seq data from the TCGA-LAML and GTEx cohorts were analyzed to evaluate EIF2S1 expression, prognostic value, associated biological programs, ssGSEA-derived immune-cell-associated signature scores, and quanTIseq-estimated immune-cell proportions. Single-cell RNA sequencing data were further examined to characterize the cellular distribution of EIF2S1 and subset-specific immune and metabolic transcriptional features. Finally, siRNA-mediated EIF2S1 knockdown assays were performed in THP-1 monocytic AML cells to assess its functional relevance. Results EIF2S1 was significantly upregulated in AML and independently associated with shorter overall survival in the TCGA-LAML cohort. High EIF2S1 expression was linked to translation initiation-related programs and immune- and myeloid-lineage-related transcriptional features, including stronger myeloid-lineage signals, weaker cytotoxic T-cell-related signatures, and increased expression of immune checkpoint and immunoregulatory genes, including LGALS9 and TGFB1. Single-cell analysis localized EIF2S1 enrichment primarily to monocyte-like subsets and associated it with mitochondrial metabolic and innate immune transcriptional programs. Functionally, EIF2S1 knockdown induced G0/G1 cell-cycle arrest, suppressed THP-1 cell proliferation, migration, and invasion, and promoted apoptosis. Conclusions EIF2S1 is associated with adverse prognosis, translation initiation-related programs, and monocyte-like immune-metabolic transcriptional states in AML. Functional findings further suggest that EIF2S1 contributes to leukemic cell fitness. These results support EIF2S1 as a potential therapeutic target requiring further experimental and clinical validation.

IGF2BP1 promotes gastric cancer progression by stabilizing HS6ST2 mRNA in an N6-methyladenosine-dependent manner

BACKGROUND Gastric cancer (GC) remains one of the leading causes of cancer-related mortality globally and is associated with poor patient prognosis, which highlights an urgent need to identify effective biomarkers and therapeutic targets. N6-methyladenosine (m6A) modification and its reader proteins play a crucial role in tumorigenesis. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) participates in carcinogenesis and serves as a reader of m6A. However, its exact function and the underlying molecular mechanisms in the progression of GC remain unknown. AIM To investigate the role of IGF2BP1 in the progression of GC. METHODS The IGF2BP1 expression in GC tissues was assessed via immunohistochemistry and correlated with clinicopathological characteristics. Gain-of-function and loss-of-function experiments were performed to explore the functional roles of IGF2BP1 and its potential downstream target in GC cells and a nude mouse xenograft model. Cell proliferation, migration, and invasion were assessed using cell counting kit-8, wound-healing, and Transwell assays. RNA sequencing, methylated RNA immunoprecipitation quantitative polymerase chain reaction, and dual-luciferase reporter assays were conducted to elucidate the molecular mechanisms involved. RESULTS The IGF2BP1 was significantly upregulated in GC tissues and was positively associated with lymph node metastasis and poor overall survival. Functionally, IGF2BP1 knockdown inhibited GC cell proliferation, migration, and invasion in vitro and attenuated tumor growth in vivo . Integrated multi-omics analysis identified heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) as a key downstream target of IGF2BP1. IGF2BP1 recognized and bound to m6A-modified sites within HS6ST2 mRNA, thereby enhancing its stability in an m6A-dependent manner. Rescue experiments confirmed that HS6ST2 mediated the oncogenic effects of IGF2BP1. Additionally, HS6ST2 knockdown inhibited the malignant characteristics of GC cells and triggered apoptosis, which was associated with inactivation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. CONCLUSION These findings demonstrated that IGF2BP1 drives GC progression by stabilizing HS6ST2 mRNA via m6A modification. The IGF2BP1/HS6ST2 axis may serve as a potential prognostic biomarker and therapeutic intervention for GC.