The role of miRNAs in the development of normal pancreas and pancreatic cancer, and their roles in tumor progression

Abstract

The microRNAs (miRNAs) have been shown to play important roles in the control of many normal biological processes including cell differentiation and organogenesis. During the development of normal pancreas, several miRNAs including miR-375, miR-7, miR-124, etc. have been shown to regulate exocrine and endocrine cell differentiation. These regulations could in part be mediated through the miRNA-mediated deregulation of transforming growth factor-β, Notch, and Hedgehog signaling, which are the signal transduction pathways that are critically involved in organogenesis during normal development. However, deregulated expression of miRNAs could also lead to the development and progression of pancreatic cancer. Moreover, miRNAs are also known to regulate the development and maintenance of pancreatic cancer stem cells and epithelial-to-mesenchymal transition phenotypic cells, which are typically responsible for drug resistance, tumor recurrence, and metastasis. Therefore, targeting specific miRNAs by oligonucleotide/nanoparticle vector delivery or regulation of miRNAs by natural agents could become novel strategies for the treatment of pancreatic cancer with better treatment outcome in combination with conventional therapeutics.