Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with less than an 8% 5-year survival rate, which has remained unchanged over the last 50 years. Early detection is particularly difficult due to the lack of disease-specific symptoms and reliable diagnostic biomarkers. Multimodality treatment including chemotherapy, radiotherapy (used sparingly) and surgery has become the standard of care for patients with PDAC. Carbohydrate antigen 19-9 (CA 19-9) is the most common diagnostic biomarker; however, it is not specific enough for asymptomatic patients. MicroRNAs (miRs/miRNAs) are small non-encoding RNA molecules, which have been related with PDAC progression and metastasis. In particular, miR-21, miR-221, miR-155 and miR-126 have to date been shown to be highly dysregulated in human malignancies including PDAC and are involved in numerous cancer-related mechanisms such as cell growth, differentiation, metastasis, invasion, and cell death. The aim of this thesis was to examine the mode of action of miR-21, miR-221, miR-155 and miR-126 in vitro for improved diagnosis and treatment of PDAC and specifically, investigate the role of the oncogenic miR-21 in cellular proliferation, migration, invasion, apoptosis, cell cycle arrest, senescence, protein content and mitochondrial function by using CRISPR/Cas9 knockouts. The findings provide promising new insights into the metastatic predisposition of PDAC through the evaluation of specific miR signature profiles (in vitro). Such miR signatures could prompt a pioneer precision medicine approach for individual PDAC cases and allow a more effective early diagnosis and control of PDAC, facilitating more effective treatment
