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

Keiichi Yonemori, Naohiko Seki, Tetsuya Idichi, Hiroshi Kurahara, Yusaku Osako, Keiichi Koshizuka, Takayuki Arai, Atsushi Okato, Yoshiaki Kita, Takaaki Arigami, Yuko Mataki, Yuko Kijima, Kosei Maemura, Shoji Natsugoe

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)70097-70115
Number of pages19
JournalOncotarget
Volume8
Issue number41
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Oncology

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    Yonemori, K., Seki, N., Idichi, T., Kurahara, H., Osako, Y., Koshizuka, K., Arai, T., Okato, A., Kita, Y., Arigami, T., Mataki, Y., Kijima, Y., Maemura, K., & Natsugoe, S. (2017). The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: Anti-tumour functions of the microRNA-216 cluster. Oncotarget, 8(41), 70097-70115. https://doi.org/10.18632/oncotarget.19591