Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3
Abstract The microRNA miR-205-5p has diverse effects in different malignancies, including cholangiocarcinoma (CCA), but its effects on CCA progression is unclear. Here we investigated the role and function of miR-205-5p in CCA. Three CCA cell lines and human serum samples were found to have much hig...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-49694-x |
| _version_ | 1797388326119931904 |
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| author | Aye Myat Mon Kitti Intuyod Sirinapha Klungsaeng Apinya Jusakul Thatsanapong Pongking Worachart Lert-itthiporn Vor Luvira Chawalit Pairojkul Tullayakorn Plengsuriyakarn Kesara Na-Bangchang Somchai Pinlaor Porntip Pinlaor |
| author_facet | Aye Myat Mon Kitti Intuyod Sirinapha Klungsaeng Apinya Jusakul Thatsanapong Pongking Worachart Lert-itthiporn Vor Luvira Chawalit Pairojkul Tullayakorn Plengsuriyakarn Kesara Na-Bangchang Somchai Pinlaor Porntip Pinlaor |
| author_sort | Aye Myat Mon |
| collection | DOAJ |
| description | Abstract The microRNA miR-205-5p has diverse effects in different malignancies, including cholangiocarcinoma (CCA), but its effects on CCA progression is unclear. Here we investigated the role and function of miR-205-5p in CCA. Three CCA cell lines and human serum samples were found to have much higher expression levels of miR-205-5p than seen in typical cholangiocyte cell lines and healthy controls. Inhibition of miR-205-5p suppressed CCA cell motility, invasion and proliferation of KKU-213B whereby overexpression of miR-205-5p promoted cell proliferation and motility of KKU-100 cells. Bioinformatics tools (miRDB, TargetScan, miRWalk, and GEPIA) all predicted various miR-205-5p targets. Experiments using miR-205-5p inhibitor and mimic indicated that homeodomain-interacting protein kinase 3 (HIPK3) was a potential direct target of miR-205-5p. Overexpression of HIPK3 using HIPK3 plasmid cloning DNA suppressed migration and proliferation of KKU-100 cells. Notably, HIPK3 expression was lower in human CCA tissues than in normal adjacent tissues. High HIPK3 expression was significantly associated with longer survival time of CCA patients. Multivariate regression analysis indicated tissue HIPK3 levels as an independent prognostic factor for CCA patients. These findings indicate that overexpression of miR-205-5p promotes CCA cells proliferation and migration partly via HIPK3-dependent way. Therefore, targeting miR-205-5p may be a potential treatment approach for CCA. |
| first_indexed | 2024-03-08T22:39:09Z |
| format | Article |
| id | doaj.art-2caccca91eee4baa8184a1aa0197e0ec |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T22:39:09Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2caccca91eee4baa8184a1aa0197e0ec2023-12-17T12:15:30ZengNature PortfolioScientific Reports2045-23222023-12-0113111310.1038/s41598-023-49694-xOverexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3Aye Myat Mon0Kitti Intuyod1Sirinapha Klungsaeng2Apinya Jusakul3Thatsanapong Pongking4Worachart Lert-itthiporn5Vor Luvira6Chawalit Pairojkul7Tullayakorn Plengsuriyakarn8Kesara Na-Bangchang9Somchai Pinlaor10Porntip Pinlaor11Medical Technology Program, Faculty of Associated Medical Sciences, Khon Kaen UniversityDepartment of Pathology, Faculty of Medicine, Khon Kaen UniversityDepartment of Parasitology, Faculty of Medicine, Khon Kaen UniversityCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen UniversityBiomedical Sciences Program, Graduate School, Khon Kaen UniversityDepartment of Biochemistry, Faculty of Medicine, Khon Kaen UniversityDepartment of Surgery, Faculty of Medicine, Khon Kaen UniversityDepartment of Pathology, Faculty of Medicine, Khon Kaen UniversityGraduate Program in Bioclinical Sciences, Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus)Graduate Program in Bioclinical Sciences, Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus)Department of Parasitology, Faculty of Medicine, Khon Kaen UniversityCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen UniversityAbstract The microRNA miR-205-5p has diverse effects in different malignancies, including cholangiocarcinoma (CCA), but its effects on CCA progression is unclear. Here we investigated the role and function of miR-205-5p in CCA. Three CCA cell lines and human serum samples were found to have much higher expression levels of miR-205-5p than seen in typical cholangiocyte cell lines and healthy controls. Inhibition of miR-205-5p suppressed CCA cell motility, invasion and proliferation of KKU-213B whereby overexpression of miR-205-5p promoted cell proliferation and motility of KKU-100 cells. Bioinformatics tools (miRDB, TargetScan, miRWalk, and GEPIA) all predicted various miR-205-5p targets. Experiments using miR-205-5p inhibitor and mimic indicated that homeodomain-interacting protein kinase 3 (HIPK3) was a potential direct target of miR-205-5p. Overexpression of HIPK3 using HIPK3 plasmid cloning DNA suppressed migration and proliferation of KKU-100 cells. Notably, HIPK3 expression was lower in human CCA tissues than in normal adjacent tissues. High HIPK3 expression was significantly associated with longer survival time of CCA patients. Multivariate regression analysis indicated tissue HIPK3 levels as an independent prognostic factor for CCA patients. These findings indicate that overexpression of miR-205-5p promotes CCA cells proliferation and migration partly via HIPK3-dependent way. Therefore, targeting miR-205-5p may be a potential treatment approach for CCA.https://doi.org/10.1038/s41598-023-49694-x |
| spellingShingle | Aye Myat Mon Kitti Intuyod Sirinapha Klungsaeng Apinya Jusakul Thatsanapong Pongking Worachart Lert-itthiporn Vor Luvira Chawalit Pairojkul Tullayakorn Plengsuriyakarn Kesara Na-Bangchang Somchai Pinlaor Porntip Pinlaor Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3 Scientific Reports |
| title | Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3 |
| title_full | Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3 |
| title_fullStr | Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3 |
| title_full_unstemmed | Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3 |
| title_short | Overexpression of microRNA-205-5p promotes cholangiocarcinoma growth by reducing expression of homeodomain-interacting protein kinase 3 |
| title_sort | overexpression of microrna 205 5p promotes cholangiocarcinoma growth by reducing expression of homeodomain interacting protein kinase 3 |
| url | https://doi.org/10.1038/s41598-023-49694-x |
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