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Objective <p>Shikonin, an active compound from the rhizome of <i>Lithospermum erythrorhizon</i>, 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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>Shikonin suppresses glioma cell proliferation, migration, invasion, and EMT by inhibiting ZEB1 expression through the p53/miR-361-5p axis.</p>

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Shikonin inhibits epithelial-mesenchymal transition in glioblastoma cells by upregulating p53 and promoting miR-361-5p level to suppress ZEB1 expression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Fengying Zhang,
  • Zhiyi Liu,
  • Yingbin Wang,
  • Lin Zuo,
  • Sicong Xu,
  • Yin Liu,
  • Hao Liang,
  • Yixue Xue

摘要

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.