journal contribution
posted on 2025-07-15, 07:20 authored by Lingjiao Meng, Haotian Wu, Jiaxiang Wu, Ping’an Ding, Jinchen He, Tongkun Li, Xiaoman Niu, Meixiang Sang, Lihua Liu <p>Supplementary Figure 8. Bioinformatics analysis revealed the characteristics of m5C genes, functional analysis, and correlation with immune cells. (A) The heat map displaying the differential expression of 15 m5C-related genes in ESCC tissues compared to adjacent tissues. (B-D) Violin and bubble plots illustrating the differential expression and pathway enrichment of NSUN2 (B), ALYREF (C), and YBX1 (D) in ESCC tissues compared to adjacent tissues. (E-G) Correlation analysis of NSUN2 (E), ALYREF (F), and YBX1 (G) with immune cell populations. (H) The specific peptide maps for NSUN2, ALYREF, and YBX1 identified by MS. ***P<0.001.</p>
Funding
National Natural Science Foundation of China (NSFC)
History
ARTICLE ABSTRACT
The lack of diagnostic and therapeutic targets precludes effective treatment of esophageal cancer, rooted in the limited mechanistic understanding of cancer initiation and progression. Nonmutational epigenetic reprogramming, including altered 5-methylcytosine (m5C) modification and circular RNA (circRNA) expression, can drive tumorigenesis and impact cancer biology. Herein, we identified upregulation of the circRNA hsa_circ_0066658 (termed as circTMEM45A) in esophageal squamous cell carcinoma (ESCC) tissues, which was correlated with advanced clinical stages and poor survival. Functionally, elevated circTMEM45A facilitated ESCC malignant progression both in vitro and in vivo. Mechanistically, circTMEM45A interacted with the methyltransferase NSUN2 and m5C readers ALYREF and YBX1, promoting the nuclear export and stability of NLRP3 mRNA to activate the NLRP3/caspase-1/IL1β inflammatory pathway. Additionally, circTMEM45A stabilized IL1B mRNA by binding to U2AF2 and stabilized IL1R1 mRNA by serving as a protein scaffold to enhance the ELAVL1(HUR) interaction, further activating the IL1β/IL1R1 proinflammatory cascade in the tumor microenvironment. These findings reveal cross-talk between circRNA and m5C modification that drives inflammatory progression, highlighting circTMEM45A as a potential diagnostic and therapeutic target in ESCC.
CircTMEM45A induces epigenomic reprogramming to support esophageal cancer development by modulating m5C modifications that converge to activate NLRP3/caspase-1/IL1β inflammatory signaling, indicating circTMEM45A could be targeted to improve detection and treatment strategies.
