Abstract 2811: Mapping the eRNAs regulatory networks associated with clinical traits in gastric cancer
Authors: Yanxin Yao, Xiangnan Zhang, Lijie Ji, Mengyue Qiu, Huahuan Liu, Kexin Chen, Ben Liu
Journal: Cancer Research (2025)

Abstract Gastric cancer (GC) is one of the top five common malignancies worldwide and the fourth leading cause of cancer-related death. Enhancer RNA (eRNA) is a type of non-coding RNA transcript originating from enhancers. In different tumors, eRNAs exhibit significant tumor specificity. In different tumors, eRNAs showed significant tumor specificity. However, the expression characteristics of eRNAs and their potential transcriptional regulatory functions still need to be further explored. More than two hundred local gastric adenocarcinoma samples were included in this study. We define two classes of eRNAs, the shorter bi-directionally transcribed 2D eRNAs and the longer 1D eRNAs. We identified about 30,000 eRNAs expressed in gastric cancer or normal gastric cancer tissues, and most of these eRNAs are located in intergenic and antisense strands of genes. Some of the eRNAs showed strong tissue specificity, aberrant activation or silencing of eRNAs leads to tumorigenesis in gastric cancer. Previous reports have demonstrated that eRNAs play a complex scaffolds role in maintaining chromatin ring stability and regulating the expression of target genes. HiC and HiChIP data were collected as evidence of spatial proximity of enhancers and promoters. Anchors annotation was performed using previously quantified eRNAs to obtain eRNA-targe gene pairs. Co-expression analysis of eRNAs and their target genes, combined with the above 3D genomic results, total of about 30,000 eRNA-target gene pairs were identified. Using edge perturbation in the gene interaction network, the edge-perturbation matrix of eRNA-target gene interaction pairs was obtained, and a value was assigned to each interaction pair. About 30,000 of these action pairs were associated with clinical characteristics. It is noteworthy that a large proportion of the action pairs were associated with the degree of differentiation of gastric cancer. To further explore the role that eRNAs play in tumor proliferation, we selected representative eRNAs and constructed CRISPRa and CRISPRi screening libraries to explore the potential role of eRNAs in gastric cancer proliferation. Bulk screening results showed that gastric cancer cells proliferated faster after activating or knocking down eRNAs. In addition, CROP-seq was used to verify the changes in target genes after activation/knockdown of eRNAs expression. Taken together, these results demonstrate that eRNAs can regulate the progression of gastric cancer by modulating the expression of their target genes, and that eRNAs can be used as potential targets for gastric cancer therapy. In summary, we have provided an in-depth characterization of the eRNAs expression landscape and its regulatory functional network in gastric cancer, and validated the eRNA-target gene action, demonstrating the possibility of eRNAs as a potential target for gastric cancer therapy. Citation Format: Yanxin Yao, Xiangnan Zhang, Lijie Ji, Mengyue Qiu, Huahuan Liu, Kexin Chen, Ben Liu. Mapping the eRNAs regulatory networks associated with clinical traits in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2811.