Genomic Profiling and Functional Analysis of let-7c miRNA-mRNA Interactions Identify SOX13 to Be Involved in Invasion and Progression of Pancreatic Cancer

Background. Pancreatic cancer is a devastating disease; its lethality is related to rapid growth and tendency to invade adjacent organs and metastasize at an early stage. Objective. The aim of this study was to identify miRNAs and their gene targets involved in the invasive phenotype in pancreatic cancer to better understand the biological behaviour and the rapid progression of this disease. Methods. miRNA profiling was performed in isogenic matched high invasive and low-invasive subclones derived from the MiaPaCa-2 cell line and validated in a panel of pancreatic cancer cell lines, tumour, and normal pancreas. Online miRNA target prediction algorithms and gene expression arrays were used to predict the target genes of the differentially expressed miRNAs. miRNAs and potential target genes were subjected to overexpression and knockdown approaches and downstream functional assays to determine their pathological role in pancreatic cancer. Results. Differential expression analysis revealed 10 significantly dysregulated miRNAs associated with invasive capacity (Student’s t-tests; P value