ESCC tissues; adjacent normal tissues; cancerous tissues; nontumor tissues; peripheral blood samples; plasma samples
TE1; TE10; KYSE30; KYSE150; KYSE410; HET-1A; HUVEC; HLEC
cell line-derived xenograft
proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); inflammation (promotes); immune regulation (promotes); m5A modification (other); mRNA stability (promotes); other pathway/process (promotes)
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; IF (Immunofluorescence); IHC (Immunohistochemistry); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; Tube Formation Assay; In Vivo Animal Model; H&E Staining; ELISA; Western Blot; Cohort Study; Survival Analysis; ROC Analysis; Bioinformatics Analysis
High circTMEM45A expression is associated with advanced clinical stage, larger tumor size, lymph node metastasis, poor overall survival and disease-free survival, and it may serve as a precise diagnostic biomarker for ESCC with diagnostic AUC 0.869 alone and 0.945 when combined with squamous cell carcinoma antigen.
circTMEM45A is an up-regulated oncogenic circRNA in ESCC that promotes malignant progression, including proliferation, migration, invasion, tumor growth and metastasis. Mechanistically, it functions as an epigenetic and protein-interaction hub, binding NSUN2/ALYREF/YBX1 to enhance m5C-mediated NLRP3 mRNA export and stability, binding U2AF2 to stabilize IL1B mRNA, and scaffolding IGF2BP2/HUR to stabilize IL1R1 mRNA, thereby activating NLRP3/caspase-1/IL1beta and IL1beta/IL1R1 inflammatory signaling. Clinically, high circTMEM45A expression correlates with advanced disease, poor survival, and potential diagnostic value in ESCC.
0.8999
Aberrant CircTMEM45A Facilitates Inflammatory Progression of Esophageal Squamous Cell Carcinoma through m5C-Mediated NLRP3 Activation.
combined biological and clinical study