Research Papers:

Regulation of actin-binding protein ANLN by antitumor miR-217 inhibits cancer cell aggressiveness in pancreatic ductal adenocarcinoma

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

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Oncotarget. 2017; 8:53180-53193. https://doi.org/10.18632/oncotarget.18261

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Tetsuya Idichi1, Naohiko Seki2, Hiroshi Kurahara1, Keiichi Yonemori1, Yusaku Osako1, 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, Kagoshima, Japan

2Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan

Correspondence to:

Naohiko Seki, email: naoseki@faculty.chiba-u.jp

Keywords: microRNA, miR-217, pancreatic ductal adenocarcinoma, ANLN, tumor-suppressor

Received: January 11, 2017    Accepted: May 08, 2017    Published: May 29, 2017


Analysis of our microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC) revealed that microRNA-217 (miR-217) was significantly reduced in cancer tissues. The aim of this study was to investigate the antitumor roles of miR-217 in PDAC cells and to identify miR-217-mediated molecular pathways involved in PDAC aggressiveness. The expression levels of miR-217 were significantly reduced in PDAC clinical specimens. Ectopic expression of miR-217 significantly suppressed cancer cell migration and invasion. Transcription of actin-binding protein Anillin (coded by ANLN) was detected by our in silico and gene expression analyses. Moreover, luciferase reporter assays showed that ANLN was a direct target of miR-217 in PDAC cells. Overexpression of ANLN was detected in PDAC clinical specimens by real-time PCR methods and immunohistochemistry. Interestingly, Kaplan–Meier survival curves showed that high expression of ANLN predicted shorter survival in patients with PDAC by TCGA database analysis. Silencing ANLN expression markedly inhibited cancer cell migration and invasion capabilities of PDAC cell lines. We further investigated ANLN-mediated downstream pathways in PDAC cells. “Focal adhesion” and “Regulation of actin binding protein” were identified as ANLN-modulated downstream pathways in PDAC cells. Identification of antitumor miR-217/ANLN-mediated PDAC pathways will provide new insights into the potential mechanisms underlying the aggressive course of PDAC.

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