TY - JOUR
T1 - The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing
T2 - Anti-tumour functions of the microRNA-216 cluster
AU - Yonemori, Keiichi
AU - Seki, Naohiko
AU - Idichi, Tetsuya
AU - Kurahara, Hiroshi
AU - Osako, Yusaku
AU - Koshizuka, Keiichi
AU - Arai, Takayuki
AU - Okato, Atsushi
AU - Kita, Yoshiaki
AU - Arigami, Takaaki
AU - Mataki, Yuko
AU - Kijima, Yuko
AU - Maemura, Kosei
AU - Natsugoe, Shoji
N1 - Funding Information:
We wish to thank the Joint Research Laboratory, Kagoshima University Graduate School of Medical and Dental Sciences, for the use of their facilities. The present study was supported by KAKENHI(C) grant 15K10801, 26462067.
Publisher Copyright:
© Yonemori et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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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U2 - 10.18632/oncotarget.19591
DO - 10.18632/oncotarget.19591
M3 - Article
AN - SCOPUS:85030263843
SN - 1949-2553
VL - 8
SP - 70097
EP - 70115
JO - Oncotarget
JF - Oncotarget
IS - 41
ER -