Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression
Abstract Objective Shikonin, an active compound from the rhizome of Lithospermum erythrorhizon, exerts anti-tumor effects in various cancers, including glioblastoma multiforme (GBM). This study explored the mechanism of Shikonin for inhibiting the migration and invasion of GBM cells, providing a rat...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-025-00956-6 |
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| author | Fengying Zhang Zhiyi Liu Yingbin Wang Lin Zuo Sicong Xu Yin Liu Hao Liang Yixue Xue |
| author_facet | Fengying Zhang Zhiyi Liu Yingbin Wang Lin Zuo Sicong Xu Yin Liu Hao Liang Yixue Xue |
| author_sort | Fengying Zhang |
| collection | DOAJ |
| description | Abstract Objective Shikonin, an active compound from the rhizome of Lithospermum erythrorhizon, exerts anti-tumor effects in various cancers, including glioblastoma multiforme (GBM). This study explored the mechanism of Shikonin for inhibiting the migration and invasion of GBM cells, providing a rationale for developing novel glioma therapies. Methods The effects of Shikonin on GBM cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were detected by CCK-8, scratch wound-healing, Transwell, and Western blot assays. The effect of Shikonin on miR-361-5p expression in GBM cells was examined by RT-qPCR and the effect of miR-361-5p inhibitor transfection on proliferation, migration, invasion, and EMT in Shikonin-treated GBM cells was examined. Shikonin’s target genes were identified and validated using dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay, focusing on its induction of miR-361-5p expression. The downstream target genes of miR-361-5p were also identified and validated under Shikonin action. A GBM cell nude mouse xenograft tumor was established to confirm the regulatory role of Shikonin. Results Shikonin inhibited cell proliferation, migration, invasion, and EMT and upregulated miR-361-5p expression in GBM cells. Shikonin upregulated the glioma-associated protein p53, which promoted miR-361-5p transcription. miR-361-5p inhibited ZEB1 expression. Therefore, Shikonin inhibited GBM cell proliferation, migration, invasion, and EMT via p53/ miR-361-5p/ ZEB1 axis in vitro and in vivo. Conclusion Shikonin suppresses glioma cell proliferation, migration, invasion, and EMT by inhibiting ZEB1 expression through the p53/miR-361-5p axis. |
| format | Article |
| id | doaj-art-282a3119d08e42f8b2e0bb307c3a5bc5 |
| institution | Kabale University |
| issn | 1471-2202 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj-art-282a3119d08e42f8b2e0bb307c3a5bc52025-08-20T04:01:24ZengBMCBMC Neuroscience1471-22022025-07-0126111310.1186/s12868-025-00956-6Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expressionFengying Zhang0Zhiyi Liu1Yingbin Wang2Lin Zuo3Sicong Xu4Yin Liu5Hao Liang6Yixue Xue7Department of Neurobiology, College of Basic Medicine, China Medical UniversityDepartment of Neurology, The First People’s Hospital of ShenyangDepartment of Neurosurgery, Central Hospital Affiliated to Shenyang Medical CollegeThe Affiliated Nanhua Hospital of Hengyang Medical School, Department of Sleep Medical centre and Department of Neurology, University of South ChinaThe Affiliated Nanhua Hospital of Hengyang Medical School, Department of Sleep Medical centre and Department of Neurology, University of South ChinaThe Affiliated Nanhua Hospital of Hengyang Medical School, Department of Sleep Medical centre and Department of Neurology, University of South ChinaThe Affiliated Nanhua Hospital of Hengyang Medical School, Department of Sleep Medical centre and Department of Neurology, University of South ChinaDepartment of Neurobiology, College of Basic Medicine, China Medical UniversityAbstract Objective Shikonin, an active compound from the rhizome of Lithospermum erythrorhizon, exerts anti-tumor effects in various cancers, including glioblastoma multiforme (GBM). This study explored the mechanism of Shikonin for inhibiting the migration and invasion of GBM cells, providing a rationale for developing novel glioma therapies. Methods The effects of Shikonin on GBM cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were detected by CCK-8, scratch wound-healing, Transwell, and Western blot assays. The effect of Shikonin on miR-361-5p expression in GBM cells was examined by RT-qPCR and the effect of miR-361-5p inhibitor transfection on proliferation, migration, invasion, and EMT in Shikonin-treated GBM cells was examined. Shikonin’s target genes were identified and validated using dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay, focusing on its induction of miR-361-5p expression. The downstream target genes of miR-361-5p were also identified and validated under Shikonin action. A GBM cell nude mouse xenograft tumor was established to confirm the regulatory role of Shikonin. Results Shikonin inhibited cell proliferation, migration, invasion, and EMT and upregulated miR-361-5p expression in GBM cells. Shikonin upregulated the glioma-associated protein p53, which promoted miR-361-5p transcription. miR-361-5p inhibited ZEB1 expression. Therefore, Shikonin inhibited GBM cell proliferation, migration, invasion, and EMT via p53/ miR-361-5p/ ZEB1 axis in vitro and in vivo. Conclusion Shikonin suppresses glioma cell proliferation, migration, invasion, and EMT by inhibiting ZEB1 expression through the p53/miR-361-5p axis.https://doi.org/10.1186/s12868-025-00956-6ShikoninGBMmiR-361-5p |
| spellingShingle | Fengying Zhang Zhiyi Liu Yingbin Wang Lin Zuo Sicong Xu Yin Liu Hao Liang Yixue Xue Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression BMC Neuroscience Shikonin GBM miR-361-5p |
| title | Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression |
| title_full | Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression |
| title_fullStr | Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression |
| title_full_unstemmed | Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression |
| title_short | Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression |
| title_sort | shikonin inhibits epithelial mesenchymal transition in glioblastoma cells by upregulating p53 and promoting mir 361 5p level to suppress zeb1 expression |
| topic | Shikonin GBM miR-361-5p |
| url | https://doi.org/10.1186/s12868-025-00956-6 |
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