Alteration of chromosome structure impacts gene expressions implicated in pancreatic ductal adenocarcinoma cells

• DOI: 10.1186/s12864-024-10109-4
• Publication Date: 2024-02-23T12:02:52Z
• Authors: Wenrui Han; Detong Shi; Qiu Yang; Xinxin Li; Jian Zhang; Cheng Peng; Fang Yan
• Keywords: Chromosome instability; Comparative genomic hybridization

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with five-year survival rate of approximately 10%. Genetic mutations are pivotal drivers in PDAC pathogenesis, but recent investigations also revealed the involvement non-genetic alterations disease development. In this study, we undertook multi-omics approach, encompassing ATAC-seq, RNA-seq, ChIP-seq, and Hi-C methodologies, to dissect gene expression arising from changes chromosome accessibility chromatin three-dimensional interactions PDAC. Results Our findings indicate that chromosomal structural can lead abnormal expressions on key genes during Notably, overexpression oncogenes FGFR2 , FOXA2 CYP2R1 CPOX be attributed augmentation promoter accessibility, coupled long-range distal elements. Additionally, our caused by genomic instability PDACs. As an example, analyzing changes, identified putative oncogenic gene, LPAR1 which shows upregulated both cell lines clinical samples. The correlated LPAR1- associated 3D genome structure state. We further demonstrated high activity required for enhanced migration vitro. Conclusions Collectively, reveal conformational alterations, addition well-known genetic mutations, critical tumorigenesis.