The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells
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 pr...
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12943-018-0760-x |
| _version_ | 1828154932580057088 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Penkhae Utaijaratrasmi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T22:46:07Z |
| format | Article |
| id | doaj.art-58c536cf8d4a40d1a113300857ef0d2f |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-11T22:46:07Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-58c536cf8d4a40d1a113300857ef0d2f2022-12-22T03:58:45ZengBMCMolecular Cancer1476-45982018-01-0117111410.1186/s12943-018-0760-xThe microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cellsPenkhae Utaijaratrasmi0Kulthida Vaeteewoottacharn1Takaaki Tsunematsu2Pranisa Jamjantra3Sopit Wongkham4Chawalit Pairojkul5Narong Khuntikeo6Naozumi Ishimaru7Yongyut Sirivatanauksorn8Ananya Pongpaibul9Peti Thuwajit10Chanitra Thuwajit11Yasusei Kudo12Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Biochemistry, Faculty of Medicine, Khon Kaen UniversityDepartment of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical SciencesDepartment of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Biochemistry, Faculty of Medicine, Khon Kaen UniversityDepartment of Pathology, Faculty of Medicine, Khon Kaen UniversityDepartment of Surgery, Faculty of Medicine, Khon Kaen UniversityDepartment of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical SciencesDepartment of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Oral Molecular Pathology, Tokushima University Graduate School of Biomedical SciencesAbstract 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.http://link.springer.com/article/10.1186/s12943-018-0760-xCancer-associated fibroblastsmicroRNA (miRNA)CholangiocarcinomaPAI-2MigrationTumor microenvironment |
| spellingShingle | 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 The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells Molecular Cancer Cancer-associated fibroblasts microRNA (miRNA) Cholangiocarcinoma PAI-2 Migration Tumor microenvironment |
| title | The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells |
| title_full | The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells |
| title_fullStr | The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells |
| title_full_unstemmed | The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells |
| title_short | The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells |
| title_sort | microrna 15a pai 2 axis in cholangiocarcinoma associated fibroblasts promotes migration of cancer cells |
| topic | Cancer-associated fibroblasts microRNA (miRNA) Cholangiocarcinoma PAI-2 Migration Tumor microenvironment |
| url | http://link.springer.com/article/10.1186/s12943-018-0760-x |
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