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

被引：82

作者：

Idichi, Tetsuya ^{[1
]}

Seki, Naohiko ^{[2
]}

Kurahara, Hiroshi ^{[1
]}

Yonemori, Keiichi ^{[1
]}

Osako, Yusaku ^{[1
]}

Arai, Takayuki ^{[2
]}

Okato, Atsushi ^{[2
]}

Kita, Yoshiaki ^{[1
]}

Arigami, Takaaki ^{[1
]}

Mataki, Yuko ^{[1
]}

Kijima, Yuko ^{[1
]}

Maemura, Kosei ^{[1
]}

Natsugoe, Shoji ^{[1
]}

机构：

[1] Kagoshima Univ, Grad Sch Med Sci, Dept Digest Surg Breast & Thyroid Surg, Kagoshima, Japan

[2] Chiba Univ, Grad Sch Med, Dept Funct Genom, Chiba, Japan

来源：

ONCOTARGET | 2017年 / 8卷 / 32期

关键词：

microRNA; miR-217; pancreatic ductal adenocarcinoma; ANLN; tumor-suppressor; TUMOR-SUPPRESSOR; PROSTATE-CANCER; DOWN-REGULATION; BREAST-CANCER; MIGRATION; INVASION; EXPRESSION; ANILLIN; CARCINOMA; PROGRESSION;

D O I：

10.18632/oncotarget.18261

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：53180 / 53193

页数：14

共 54 条

[1] OncoLnc: linking TCGA survival data to mRNAs, miRNAs, and lncRNAs [J].