circRNA basic information
circBase ID: hsa_circ_0066658
Name: hsa_circ_TMEM45A
Synonym: circTMEM45A
Host Gene: TMEM45A
Genomic location(hg19): chr3:100274052-100287811:+
Genomic location(hg38): chr3:100555208-100568967:+
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005580
MONDO name: esophageal squamous cell carcinoma
Disease details: esophageal squamous cell carcinoma
Disease DO ID:
3748
Disease MeSH ID:
C562729; D000077277
Disease NCIt ID:
C4024
Disease ICD11 ID:
1417891145
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

ESCC tissues; adjacent normal tissues; cancerous tissues; nontumor tissues; peripheral blood samples; plasma samples

Cell lines:

TE1; TE10; KYSE30; KYSE150; KYSE410; HET-1A; HUVEC; HLEC

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: NSUN2, ALYREF, YBX1, NLRP3 mRNA, IL1B mRNA, U2AF2, IL1R1 mRNA, IGF2BP2, HUR, ELAVL1(HUR)
Associated microRNA: -
Biological function: Facilitates ESCC malignant progression; promotes proliferation, migration, invasion, tumor growth and metastasis; promotes inflammatory response and inflammatory progression; may serve as a diagnostic and prognostic biomarker.
Molecular mechanism: circTMEM45A acts through circRNA-protein and epigenetic m5C-related mechanisms: it interacts with NSUN2, ALYREF and YBX1 to promote m5C modification, nuclear export and stability of NLRP3 mRNA, activates the NLRP3/caspase-1/IL1beta inflammatory pathway, binds U2AF2 to stabilize IL1B mRNA, and serves as a scaffold enhancing IGF2BP2/HUR interaction to stabilize IL1R1 mRNA and activate the IL1beta/IL1R1 proinflammatory cascade.
Biological pathway or process:

proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); inflammation (promotes); immune regulation (promotes); m5A modification (other); mRNA stability (promotes); other pathway/process (promotes)

Detected method:
Q
H
S
Validation methods:

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

Clinical significance:

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.

Description:

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.

Confidence score:

0.8999

Other information
Title:

Aberrant CircTMEM45A Facilitates Inflammatory Progression of Esophageal Squamous Cell Carcinoma through m5C-Mediated NLRP3 Activation.

Journal: Cancer research
Published: 2025
PubMed ID: 40215175
Study type:

combined biological and clinical study

Data availability: GSE293235; GSE291375; TCGA esophageal carcinoma mRNA-seq data at http://firebrowse.org/? cohort¼ESCA&download_dialog¼true; GeneCards at https://www.genecards.org; CircNET at https:// awi.cuhk.edu.cn/∼CircNet/php/index.php; RBPmap at http://rbpmap. technion.ac.il/; StarBase at http://starbase.sysu.edu.cn/; Supplementary Materials; Supplementary data for this article are available at Cancer Research Online (http:// cancerres.aacrjournals.org/).
Code availability: -