Investigating the role of long-noncoding RNA (LINC001) in the initiation of pancreatic ductal adenocarcinoma

Title Investigating the role of long-noncoding RNA (LINC001) in the initiation of pancreatic ductal adenocarcinoma
Acronym
Start date 2023-08-01
End date 2026-07-31
Sponsor Anita Kurilla
Institution University of Copenhagen

Associated cell lines

Project Description

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-associated deaths and has the lowest survival rate of all cancers. Although the tumor is detected late in the progression of the disease, PDAC initiation occurs years before the diagnosis. Thus, there is a large window of opportunity for early detection and treatment. However, experimental models that mimic the precursor lesions of human PDAC development are lacking and the molecular underpinnings of tumor initiation are unknown. Our aim is to model human PDAC initiation using human embryonic stem cells (HUES cells). The development of precursor lesions is driven by an activating mutation in the Kirsten Rat Sarcoma (KRAS) oncogene, altered in virtually all human PDACs and considered the driver somatic mutation in the human disease. The Arnes group has previously performed extensive gene expression profiling of early and advanced tumor samples and non-cancerous pancreas. These data suggest that the noncoding RNA transcribed from regulatory elements of pancreas development are necessary for cancer onset. The aims of this project are to investigate the function of ncRNAs in regulating the initiation of PDAC and identify the downstream targets in PDAC development. To achieve this goal, we will use stem cell models and next-generation sequencing.