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

The RNA-binding protein La/SSB is associated with HNSCC progression and TFAP2C/FSCN1-linked transcriptional regulation.

Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive progression, frequent therapeutic resistance, and poor clinical outcomes. Although the RNA-binding protein La/SSB is aberrantly expressed in multiple malignancies, its functional and mechanistic role in HNSCC remains incompletely understood. Here, by integrating transcriptomic and chromatin accessibility profiling with comprehensive in vitro and in vivo analyses, we identify La/SSB as a putative regulator associated with HNSCC progression and cisplatin (CDDP) resistance. La/SSB was markedly upregulated in HNSCC tissues and cell lines, and elevated expression was associated with unfavorable survival. Genetic depletion of La/SSB suppressed proliferation, migration, and invasion, promoted apoptosis, and reduced tumor growth and metastatic colonization, whereas ectopic expression exerted the opposite effects. Multi-omics analyses implicated FSCN1 as a functionally relevant downstream candidate associated with La/SSB-dependent phenotypes. Mechanistically, La/SSB depletion was associated with reduced H3K27ac enrichment and diminished TFAP2C occupancy at the FSCN1 promoter, supporting a TFAP2C/FSCN1-linked regulatory framework. Importantly, loss of La/SSB significantly enhanced CDDP responsiveness in the PDO model established in this study and in vivo conditional knockout models. Clinically, elevated La/SSB showed independent prognostic value, whereas TFAP2C and FSCN1 supported a biologically associated regulatory framework linked to aggressive disease features. Collectively, our findings identify La/SSB as a clinically relevant factor associated with HNSCC progression and CDDP responsiveness, and support a TFAP2C/FSCN1-linked regulatory framework that may contribute to malignant phenotypes.

Circ17399 RNA promotes melanoma progression through the miR-150-3p/ITM2C Axis and ALKBH5-mediated FOXM1 m6A modification

Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy with a poor prognosis, necessitating the exploration of novel molecular mechanisms driving its progression. CircRNA, which have emerged as critical regulators in cancer biology, have been implicated in various tumorigenic processes. However, their specific roles in SKCM remain inadequately understood. Bioinformatics analyses of TCGA and GEO datasets identified circ17399 as a candidate oncogenic circRNA. Functional validation was performed using in vitro (A375, A2058 cells) and in vivo models. Techniques included qRT-PCR, dual-luciferase reporter assays, RNA FISH, Western blot, Transwell assays, and MeRIP-qPCR. Circ17399 knockdown/overexpression, miR-150-3p modulation, and ALKBH5/FOXM1 interaction studies were conducted to dissect its regulatory network. Circ17399 was significantly upregulated in SKCM tissues and correlated with poor prognosis. Mechanistically, circ17399 sponged miR-150-3p to derepress ITM2C, enhancing SKCM cell proliferation, migration, and invasion. Concurrently, circ17399 bound ALKBH5, reducing m6A methylation on FOXM1 mRNA, thereby stabilizing FOXM1 and promoting tumor progression. In vivo, circ17399 knockdown suppressed tumor growth and metastasis, while overexpression exacerbated malignancy. Circ17399 promotes melanoma progression by competitively binding miR-150-3p to upregulate ITM2C and recruiting ALKBH5 to reduce m6A methylation of FOXM1, enhancing its stability and oncogenic function. These findings unveil a dual-axis regulatory mechanism in SKCM pathogenesis and position circ17399 as a promising diagnostic biomarker and actionable therapeutic target for melanoma intervention.

PPIB interacts with MET to activate the PI3K-AKT pathway and promote head and neck squamous cell carcinoma pathogenesis

IGF2BP3 promotes esophageal squamous cell carcinoma progression by regulating global protein translation.

Esophageal squamous cell carcinoma (ESCC) has a consistently high incidence and poor prognosis. The RNA-binding protein insulin-like growth factor 2-binding protein 3 (IGF2BP3) has been implicated in the progression of various malignant tumors. However, the contribution of IGF2BP3 in ESCC and its underlying molecular mechanisms remain elusive. Here, we found that IGF2BP3 was upregulated in ESCC tissues, and elevated IGF2BP3 expression correlates with reduced overall survival. Through gain- and loss-of-function assays, IGF2BP3 significantly enhanced ESCC cell proliferation and migration in vitro and accelerated tumor growth and metastasis in vivo. Mechanistically, IGF2BP3 directly binds to multiple ribosomal protein L (RPL) mRNAs (e.g., RPL12, RPL8, RPL17) and enhances their stability, thereby promoting ribosomal assembly and improving global translation efficiency. This leads to substantial upregulation of oncoproteins such as c-Myc and β-catenin. Collectively, our findings reveal an oncogenic role of IGF2BP3 in ESCC progression and highlight it as a promising molecular target for further therapeutic exploration in ESCC.

CircGABRB2_006 Drives Malignant Progression and EMT in Papillary Thyroid Carcinoma via the miR-296-5p/FGFR1 Axis.

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.