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Oncotarget. 2017 Jul 26;8(41):70097-70115. doi: 10.18632/oncotarget.19591. eCollection 2017 Sep 19.

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

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Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890-8520, Japan.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.


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 siFOXQ1 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.


FOXQ1; expression signature; miR-216b-3p; microRNA; pancreatic ductal adenocarcinoma

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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