Oncotarget

Research Papers:

MicroRNA-23a promotes pancreatic cancer metastasis by targeting epithelial splicing regulator protein 1

Guo Wu, Zhonghu Li, Peng Jiang, Xi Zhang, Yingqiang Xu, Kai Chen and Xiaowu Li _

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Oncotarget. 2017; 8:82854-82871. https://doi.org/10.18632/oncotarget.20692

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Abstract

Guo Wu1, Zhonghu Li1, Peng Jiang1, Xi Zhang1, Yingqiang Xu1, Kai Chen1 and Xiaowu Li1

1Department of Hepatobiliary Surgery Institute, South Western Hospital, Third Military Medical University, Chongqing 400038, China

Correspondence to:

Xiaowu Li, email: [email protected]

Keywords: microRNA-23a (miR-23a), pancreatic cancer, ESRP1, epithelial-mesenchymal transition (EMT), TGF-β1

Received: November 23, 2016     Accepted: May 29, 2017     Published: August 24, 2017

ABSTRACT

miR-23a plays vital roles in various cancer metastases. Here, we found that miR-23a expression was significantly up-regulated in pancreatic cancer tissues compared with adjacent normal tissues. miR-23a up-regulation was significantly associated with differentiated degree, lymphoid nodal status, tumor invasion and poor survival rate in pancreatic cancer patients. We also found that miR-23a expression was significantly up-regulated in lymph node metastatic tissues and in pancreatic cancer cells that underwent epithelial-mesenchymal transition (EMT). miR-23a down-regulation blocked TGF-β1-induced EMT and reversed the phenotype of EMT in Panc-1 cells. Furthermore, miR-23a down-regulation inhibited Panc-1 cells migration and invasion in vitro and liver metastases in vivo. But the effect of miR-23a up-regulation in Aspc-1 cells was opposite to that of miR-23a down-regulation in Panc-1 cells. Epithelial splicing regulatory protein 1 (ESRP1) was identified as a direct target of miR-23a. Restoration of ESRP1 rescued the effect of miR-23a on pancreatic cancer cell progression. Moreover, miR-23a up-regulation in Aspc-1 cells induced a shift in CD44 expression from variant isoforms (CD44v) to the standard isoform (CD44s) together with increased FGFR2 IIIc mRNA levels, and decreased FGFR2 IIIb expression during EMT. But the effect of miR-23a down-regulation in Panc-1 cells was opposite to that of miR-23a up-regulation in Aspc-1 cells. In addition, the effect of miR-23a up-regulation was partly reversed by ESRP1 over-expression. Taken together, our findings indicated that miR-23a functions as an oncogene by regulating ESRP1 in pancreatic cancer.


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