The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: anti-tumour functions of the microRNA-216 cluster.

We analysed the RNA sequence-based microRNA (miRNA) signature of pancreatic ductal adenocarcinoma (PDAC). Aberrantly expressed miRNAs were successfully identified in this signature. Using the PDAC signature, we focused on 4 clustered miRNAs, miR-216a-5p , miR-216a-3p , miR-216b-5p and miR-216b-3p on human chromosome 2p16.1. All members of the miR-216 cluster were significantly reduced in PDAC specimens. Ectopic expression of these miRNAs suppressed cancer cell aggressiveness, suggesting miR-216 cluster as anti-tumour miRNAs in PDAC cells. The impact of miR-216b-3p (passenger strand of pre- miR-216b ) on cancer cells is still ambiguous. Forkhead box Q1 ( FOXQ1 ) was directly regulated by miR-216b-3p and overexpression of FOXQ1 was confirmed in clinical specimens. High expression of FOXQ1 predicted a shorter survival of patients with PDAC by Kaplan-Meier analysis. Loss-of-function assays showed that cancer cell migration and invasion activities were significantly reduced by si FOXQ1 transfectants. We investigated pathways downstream from FOXQ1 by using genome-wide gene expression analysis. Identification of the miR-216-3p/FOXQ1 -mediated network in PDAC should enhance understanding of PDAC aggressiveness at the molecular level.