circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling
Abstract Background Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissue...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Molecular Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s10020-020-00159-1 |
| _version_ | 1819070469628755968 |
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| author | Long-Wei Huo Ya-Fei Wang Xiao-Bin Bai Hu-Lin Zheng Mao-De Wang |
| author_facet | Long-Wei Huo Ya-Fei Wang Xiao-Bin Bai Hu-Lin Zheng Mao-De Wang |
| author_sort | Long-Wei Huo |
| collection | DOAJ |
| description | Abstract Background Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear. Methods circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels. Results circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes. Conclusion circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma. |
| first_indexed | 2024-12-21T17:06:26Z |
| format | Article |
| id | doaj.art-6979ac94ae3c40b7a6320c68277a86e9 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-21T17:06:26Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-6979ac94ae3c40b7a6320c68277a86e92022-12-21T18:56:30ZengBMCMolecular Medicine1076-15511528-36582020-04-0126111510.1186/s10020-020-00159-1circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signalingLong-Wei Huo0Ya-Fei Wang1Xiao-Bin Bai2Hu-Lin Zheng3Mao-De Wang4Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiao Tong UniversityDepartment of Neurosurgery, Yulin First Hospital Affiliated to Xi’an Jiao Tong UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiao Tong UniversityDepartment of Neurosurgery, Yulin First Hospital Affiliated to Xi’an Jiao Tong UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiao Tong UniversityAbstract Background Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear. Methods circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels. Results circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes. Conclusion circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.http://link.springer.com/article/10.1186/s10020-020-00159-1circKIF4AGliomamiR-139-3pWnt5aProliferationMigration |
| spellingShingle | Long-Wei Huo Ya-Fei Wang Xiao-Bin Bai Hu-Lin Zheng Mao-De Wang circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling Molecular Medicine circKIF4A Glioma miR-139-3p Wnt5a Proliferation Migration |
| title | circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling |
| title_full | circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling |
| title_fullStr | circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling |
| title_full_unstemmed | circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling |
| title_short | circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling |
| title_sort | circkif4a promotes tumorogenesis of glioma by targeting mir 139 3p to activate wnt5a signaling |
| topic | circKIF4A Glioma miR-139-3p Wnt5a Proliferation Migration |
| url | http://link.springer.com/article/10.1186/s10020-020-00159-1 |
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