Genome-wide characterization of extrachromosomal circular DNA in gastric cancer and its potential role in carcinogenesis and cancer progression.
Xianming JiangXiaoguang PanWenchao LiPeng HanJiaying YuJing LiHaoran ZhangWei LvYing ZhangYulong HeXi XiangPublished in: Cellular and molecular life sciences : CMLS (2023)
Extrachromosomal circular DNAs (eccDNAs) carrying random genomic segments are broadly found across different cancer types, but their molecular functions and impact in gastric cancer (GC) are rarely known. In this study, we aimed to investigate the potential role of eccDNA in GC. Using the Circle-seq strategy, we observed the eccDNA abundance in gastric cancer tissues (GCT) was aberrantly higher than that of normal adjacent tissues (NAT). The high abundance of eccDNAs carrying oncogene-segments in GCT may represent the DNA damage products of amplified oncogenes. Analysis of GCT over-represented eccDNA carrying enhancer (eccEnhancer) based on data from FANTOM5 project combined with TCGA database suggested the GC over-represented eccEnhancers may contribute to development of GC. GC over-represented eccDNAs carrying pre-miRNA (eccMIR) were enriched to multiple cancer-relevant signal pathways by KEGG analysis. We then synthesized the top six GC over-represented eccMIRs and found four of them enabled high expression of miRNAs and down-regulation of miRNA-target genes in MGC803 cells. Furthermore, we observed the inheritance of GC over-represented eccMIRs benefited host cell proliferation and promoted the aggressive features of host cells. Altogether, this study revealed the GC over-represented eccDNAs carrying functional genomic segments were related to the carcinogenesis of GC and presented the capability to facilitate cancer progression, suggesting the cancerous eccDNAs may serve as a dynamic reservoir for genome plasticity and rapid adaptive evolution of cancer. Therefore, blocking the pathways for eccDNAs generation may provide a novel therapeutic strategy for the treatment of gastric cancer.
Keyphrases
- copy number
- genome wide
- papillary thyroid
- squamous cell
- dna damage
- gas chromatography
- cell proliferation
- induced apoptosis
- lymph node metastasis
- gene expression
- squamous cell carcinoma
- emergency department
- binding protein
- climate change
- young adults
- single cell
- cell cycle
- machine learning
- microbial community
- artificial intelligence
- electronic health record
- endoplasmic reticulum stress
- adverse drug
- cell free
- antibiotic resistance genes
- circulating tumor
- rna seq
- genome wide identification