Utaijaratrasmi, Penkhae Mahidol University
Vaeteewoottacharn, Kulthida Khon Kaen University
Tsunematsu, Takaaki Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Jamjantra, Pranisa Mahidol University
Wongkham, Sopit Khon Kaen University
Pairojkul, Chawalit Khon Kaen University
Khuntikeo, Narong Khon Kaen University
Ishimaru, Naozumi Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Sirivatanauksorn, Yongyut Mahidol University
Pongpaibul, Ananya Mahidol University
Thuwajit, Peti Mahidol University
Thuwajit, Chanitra Mahidol University
Kudo, Yasusei Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
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.
BioMed Central|Springer Nature
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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