181 JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Special Issue No. 2 – May 2017. [ISSN 1590-8577] REVIEW ARTICLE JOP. J Pancreas (Online) 2017 May 18; S(2):181-186. INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM Role of MicroRNA in IPMN Lesions Andrea Palloni 1 , Veronica Mollica 1 , Manuela Ferracin 1 , Giorgio Frega 1 , Ilaria Maggio 1 , Elisa Giovannetti 2,3 , Chiara Caparello 4 , Guido Biasco 1,5 , Ingrid Garajová 1,5 ¹Department of Experimental, Diagnostic and Speciality Medicine (DIMES), Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy 2 Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; 3 Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy 4 Department of Medical Oncology, University Hospital of Pisa, Pisa, Italy 5 Interdepartmental Centre of Cancer Research “Giorgio Prodi”, University of Bologna, Bologna, Italy ABSTRACT Pancreatic ductal adenocarcinoma is one of the leading causes of cancer related death which could be explained by typically late diagnosis and chemo- radioresistance. The majority of pancreatic ductal adenocarcinoma develops from three precursor lesions, including intraductal papillary mucinous neoplasm. Therefore, an effective screening tool to detect early stages of pancreatic ductal adenocarcinoma or its precursor lesions is needed. MicroRNAs belong to a class of short non-coding RNAs and act as tumor oncogenes or tumor suppressors. They play an important role in life-cycle of normal cells, as well as cancer cells, supporting their cancerogenous and metastatic potential. Different panels of upregulated and downregulated miRNAs have been associated with pancreatic ductal adenocarcinoma and its precursor lesions. In the present review, we discuss the recent studies focusing on miRNAs in intraductal papillary mucinous neoplasm. A summary of the most important miRNAs involved in intraductal papillary mucinous neoplasm pathogenesis is provided. Identification of key miRNA networks in pancreatic ductal adenocarcinoma precursors might provide diagnostic tools for early detection and subsequently extended life expectancy for this disease. Received January 30th, 2017-Accepted March 06th, 2017 Keywords Biomarkers; Diagnosis; MicroRNAs Abbrevations EUS-FNA endoscopic-ultrasound fine-needle aspiration; IPMN intraductal papillary mucinous neoplasm; PDAC pancreatic ductal adenocarcinoma Correspondence Ingrid Garajová Department of Experimental Diagnostic and Speciality Medicine (DIMES), Sant’Orsola-Malpighi Hospital University of Bologna, Via Massarenti 9, 40138 Bologna, Italy Interdepartmental Centre of Cancer Research “Giorgio Prodi” Sant’Orsola-Malpighi Hospital, Padiglione 13, V piano, Via Massarenti, 11 University of Bologna, 40138 Bologna, Italy Phone +390512144536 Fax +390516364536 E-mail ingegarajova@gmail.com INTRADUCTUAL PAPILLARY MUCINOUS NEO- PLASM (IPMN) Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasm with poor prognosis, mainly due to its late diagnosis and resistance to current anticancer treatments. Only less than 6% of PDAC patients survive 5-years after initial diagnosis [1, 2]. Surgical asportation of PDAC is the only way which could lead to complete cancer cure, though, only 15-20% of patients are resecable at the moment of diagnosis [3, 4]. Early detection and surgical resection can increase PDAC 5-year survival rate up to 50% for stage I [5, 6, 7]. The majority of PDAC develop from three precursor lesions: pancreatic intraepithelial lesions (PanIN), intraductual papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN), that may progress to cancer following different pathways [8]. The malignant transformation of IPMN is characterized by an orderly adenoma-carcinoma sequence from low-grade to high-grade dysplasia and further to invasive carcinoma and the risk of cancer development and consequently the management of precursor lesions derive from stratification of patients on the basis of specific physical and imaging findings according to worldwide accepted guidelines [9, 10]. In general, they can be divided into main duct type (MD-IPMN) or branch duct type (BD-IPMN). The malignant potential is higher for MD-IPMN (around 44%- 48%) compared to BD-IPMNs, which only carry a 11%- 17% risk of malignant transformation [11, 12, 13]. Given the aggressive nature of PDAC, detection of precursor lesions with malignant potentional would be critical to increasing the survival of these patients. Nowadays, no reliable biomarkers for early detection of PDAC or its precursors exist. Specific miRNAs have been found to be deregulated in PDAC and IPMN, suggesting their role as potential early biomarkers of this disease. MICRORNAs MicroRNAs (miRNAs) are short non-coding RNAs that contain circa 19-24 nucleotides. Most miRNA loci are found in non-coding intronic transcription regions and therefore do not encode any proteins. Remarkably, each miRNA can regulate the expression of numerous target genes and also