TY - JOUR
T1 - Gene regulation by antitumor miR-204-5p in Pancreatic Ductal adenocarcinoma
T2 - The clinical significance of direct RACGAP1 Regulation
AU - Khalid, Muhammad
AU - Idichi, Tetsuya
AU - Seki, Naohiko
AU - Wada, Masumi
AU - Yamada, Yasutaka
AU - Fukuhisa, Haruhi
AU - Toda, Hiroko
AU - Kita, Yoshiaki
AU - Kawasaki, Yota
AU - Tanoue, Kiyonori
AU - Kurahara, Hiroshi
AU - Mataki, Yuko
AU - Maemura, Kosei
AU - Natsugoe, Shoji
N1 - Funding Information:
Funding: This study was supported by KAKENHI grants 18K16322, 18K08687, 18K08626, 17H04285, 16K19945, 18K15219, 16H05462(B) and 15K10801(C).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3
Y1 - 2019/3
N2 - Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in PDAC pathogenesis. Cancer cell migration and invasion were significantly inhibited by ectopic expression of miR-204-5p in PDAC cells. Comprehensive gene expression analyses and in silico database searches revealed 25 putative targets regulated by miR-204-5p in PDAC cells. Among these target genes, high expression levels of RACGAP1, DHRS9, AP1S3, FOXC1, PRP11, RHBDL2 and MUC4 were significant predictors of a poor prognosis of patients with PDAC. In this study, we focused on RACGAP1 (Rac guanosine triphosphatase-activating protein 1) because its expression was most significantly predictive of PDAC pathogenesis (overall survival rate: p = 0.0000548; disease-free survival rate: p = 0.0014). Overexpression of RACGAP1 was detected in PDAC clinical specimens, and its expression enhanced the migration and invasion of PDAC cells. Moreover, downstream genes affected by RACGAP1 (e.g., MMP28, CEP55, CDK1, ANLN and S100A14) are involved in PDAC pathogenesis. Our strategy to identify antitumor miRNAs and their target genes will help elucidate the molecular pathogenesis of PDAC. View Full-Text.
AB - Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in PDAC pathogenesis. Cancer cell migration and invasion were significantly inhibited by ectopic expression of miR-204-5p in PDAC cells. Comprehensive gene expression analyses and in silico database searches revealed 25 putative targets regulated by miR-204-5p in PDAC cells. Among these target genes, high expression levels of RACGAP1, DHRS9, AP1S3, FOXC1, PRP11, RHBDL2 and MUC4 were significant predictors of a poor prognosis of patients with PDAC. In this study, we focused on RACGAP1 (Rac guanosine triphosphatase-activating protein 1) because its expression was most significantly predictive of PDAC pathogenesis (overall survival rate: p = 0.0000548; disease-free survival rate: p = 0.0014). Overexpression of RACGAP1 was detected in PDAC clinical specimens, and its expression enhanced the migration and invasion of PDAC cells. Moreover, downstream genes affected by RACGAP1 (e.g., MMP28, CEP55, CDK1, ANLN and S100A14) are involved in PDAC pathogenesis. Our strategy to identify antitumor miRNAs and their target genes will help elucidate the molecular pathogenesis of PDAC. View Full-Text.
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U2 - 10.3390/cancers11030327
DO - 10.3390/cancers11030327
M3 - Article
AN - SCOPUS:85064333593
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 3
M1 - 327
ER -