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.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Utaijaratrasmi P,Vaeteewoottacharn K,Tsunematsu T,Jamjantra P,Wongkham S,Pairojkul C,Khuntikeo N,Ishimaru N,Sirivatanauksorn Y,Pongpaibul A,Thuwajit P,Thuwajit C,Kudo Ydoi
10.1186/s12943-018-0760-xsubject
Has Abstractpub_date
2018-01-18 00:00:00pages
10issue
1issn
1476-4598pii
10.1186/s12943-018-0760-xjournal_volume
17pub_type
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