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Open Access 01-12-2018 | Research

The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells

Authors: Penkhae Utaijaratrasmi, Kulthida Vaeteewoottacharn, Takaaki Tsunematsu, Pranisa Jamjantra, Sopit Wongkham, Chawalit Pairojkul, Narong Khuntikeo, Naozumi Ishimaru, Yongyut Sirivatanauksorn, Ananya Pongpaibul, Peti Thuwajit, Chanitra Thuwajit, Yasusei Kudo

Published in: Molecular Cancer | Issue 1/2018

Abstract

Background

Cholangiocarcinoma (CCA) has an abundance of tumor stroma which plays an important role in cancer progression via tumor-promoting signals. This study aims to explore the microRNA (miRNA) profile of CCA-associated fibroblasts (CCFs) and the roles of any identified miRNAs in CCA progression.

Methods

miRNA expression profiles of CCFs and normal skin fibroblasts were compared by microarray. Identified downregulated miRNAs and their target genes were confirmed by real-time PCR. Their binding was confirmed by a luciferase reporter assay. The effects of conditioned-media (CM) of miRNA mimic- and antagonist-transfected CCFs were tested in CCA migration in wound healing assays. Finally, the levels of miRNA and their target genes were examined by real-time PCR and immunohistochemistry in clinical CCA samples.

Results

miR-15a was identified as a downregulated miRNA in CCFs. Moreover, PAI-2 was identified as a novel target gene of miR-15a. Recombinant PAI-2 promoted migration of CCA cells. Moreover, CM from miR-15a mimic-transfected CCFs suppressed migration of CCA cells. Lower expression of miR-15a and higher expression of PAI-2 were observed in human CCA samples compared with normal liver tissues. Importantly, PAI-2 expression correlated with poor prognosis in CCA patients.

Conclusions

These findings highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA patients.

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Title: The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells
Authors: Penkhae Utaijaratrasmi
Kulthida Vaeteewoottacharn
Takaaki Tsunematsu
Pranisa Jamjantra
Sopit Wongkham
Chawalit Pairojkul
Narong Khuntikeo
Naozumi Ishimaru
Yongyut Sirivatanauksorn
Ananya Pongpaibul
Peti Thuwajit
Chanitra Thuwajit
Yasusei Kudo
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/s12943-018-0760-x

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