Oncotarget

Research Papers:

Twist promotes angiogenesis in pancreatic cancer by targeting miR-497/VEGFA axis

An Liu, Chenggang Huang, Xuehong Cai, Jia Xu and Dinghua Yang _

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Oncotarget. 2016; 7:25801-25814. https://doi.org/10.18632/oncotarget.8269

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Abstract

An Liu1, Chenggang Huang2, Xuehong Cai2, Jia Xu2, Dinghua Yang1

1Department of Hepatobiliary Surgery, NanFang Hospital of Southern Medical University, Guangzhou, 510515 Guangdong, China

2Department of General Surgery, The First People Hospital of Yueyang, Yueyang, 414000 Hunan, China

Correspondence to:

Dinghua Yang, email: [email protected]

Keywords: microRNA, tumor biology, proliferation, metastasis

Received: January 09, 2016     Accepted: March 07, 2016     Published: March 22, 2016

ABSTRACT

Angiogenesis is a critical step in the growth and dissemination of malignant diseases, including pancreatic cancer. Twist has been shown to stimulate angiogenesis in the tumor site. However, whether Twist contributes to angiogenesis in pancreatic cancer remains unknown. In this paper, we found that the expression of Twist was significantly increased in human pancreatic cancer cell lines and pancreatic cancer specimens. It is also closely engaged to adverse clinical feature, diminished survival and angiogenesis in pancreatic cancer patients. The up-regulation of Twist was found to be promoting cell growth, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs) in vitro. By contrast, the silencing of Twist inhibited orthotopic xenograft tumor growth, metastasis and angiogenesis. Subsequent investigations disclosed that Twist was regulated by miR-497 directly, leading to the increased level of Vascular Endothelial Growth Factor-A (VEGFA). Moreover, gain-of-function and loss-of-function studies demonstrated that miR-497 could suppress the pro-proliferative, angiogenic and metastatic ability of pancreatic cancer cells. The ectopic expression of VEGFA obviously abrogated the anti-angiogenic effect induced by Twist knockdown, whereas the silencing of VEGFA markedly rescued the pro-angiogenic effect of Twist. By analyzing the expression levels of miR-497, Twist was found inversely correlated with miR-497 in pancreatic cancer tissues, and a positive correlation was found between Twist and VEGFA levels in pancreatic cancer specimens. In conclusion, our results suggested that the Twist/miR-497/VEGFA axis is significantly correlated with metastasis and angiogenesis in pancreatic cancer.


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