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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
Faculty of Medicine, Khon Kaen University
Khon Kaen University
Faculty of Medicine, Siriraj Hospital, Mahidol University
Tokushima University
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 18-Jan-2018
Citation: Molecular Cancer. Vol.17, No.1 (2018)
Abstract: © 2018 The Author(s). 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.
ISSN: 14764598
Appears in Collections:Scopus 2018

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