A set of 72 differentially expressed miRNAs provide a molecular signature for pancreatic cancer

MicroRNAs (miRNAs) are short single-stranded RNA molecules that have a critical role in the regulation of gene expression. Alterations in miRNA expression levels have been observed in multiple tumor types and there is clear evidence on their active involvement in cancer development. Here, a comprehensive miRNA expression profiling in 16 pancreatic cancer cell lines and four normal pancreatic samples provided a specific molecular signature for pancreatic cancer and enabled us to identify 72 differentially expressed miRNAs with approximately half of them being up- and half downregulated in cancer cells as compared to normal samples. Of these, miR-31 was selected for further functional analyses based on its interesting “on-off” type expression profile, i.e. very low or even absent expression in normal pancreas and in six of the pancreatic cancer samples but extremely high expression in the remaining ten cell lines. Quite unexpectedly, both the inhibition of miR-31 in AsPC-1 and HPAF-II pancreatic cancer cells with high endogenous expression and forced expression of miR-31 in MIA PaCa-2 with low endogenous levels led to reduced cell proliferation, migration and invasion. More importantly, in AsPC-1 cells further enhancement of miR-31 also resulted in reduced cell migration and invasion, implicating that the level of miR-31 is critical for these phenotypes. We also identified novel miR-31 target genes, APBB2 and RSBN1, that might contribute to cancer pathogenesis. This study highlights a specific miRNA expression pattern in pancreatic cancer and reveals that manipulation of miR-31 expression leads to reduced cell migration and invasion in pancreatic cancer. 16 pancreatic cancer cell lines and 4 normal pancreatic RNA samples were hybridized on Agilent vs1 miRNA microarrays. Pool of four normal samples was hybridized on each slide to allow normalization between slides.