Oncotarget

Research Papers:

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 and Shoji Natsugoe

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Oncotarget. 2017; 8:70097-70115. https://doi.org/10.18632/oncotarget.19591

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Abstract

Keiichi Yonemori1, Naohiko Seki2, Tetsuya Idichi1, Hiroshi Kurahara1, Yusaku Osako1, Keiichi Koshizuka2, Takayuki Arai2, Atsushi Okato2, Yoshiaki Kita1, Takaaki Arigami1, Yuko Mataki1, Yuko Kijima1, Kosei Maemura1 and Shoji Natsugoe1

1Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890-8520, Japan

2Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan

Correspondence to:

Naohiko Seki, email: [email protected]

Keywords: pancreatic ductal adenocarcinoma, microRNA, expression signature, miR-216b-3p, FOXQ1

Received: February 07, 2017     Accepted: June 26, 2017     Published: July 26, 2017

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.


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