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

  • BMC Neurosci. 2025 Jul 1;26(1):37. doi: 10.1186/s12868-025-00956-6.
Fengying Zhang  #  1  2 ,  Zhiyi Liu  #  3 ,  Yingbin Wang  4 ,  Lin Zuo  2 ,  Sicong Xu  2 ,  Yin Liu  2 ,  Hao Liang  2 ,  Yixue Xue  5  6
Affiliations
  • 1. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, China.
  • 2. The Affiliated Nanhua Hospital of Hengyang Medical School, Department of Sleep Medical centre and Department of Neurology, University of South China, Hengyang, China.
  • 3. Department of Neurology, The First People's Hospital of Shenyang, Shenyang, China.
  • 4. Department of Neurosurgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.
  • 5. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, China. [email protected].
  • 6. Institute of Pathophysiology, China Medical University, Shenyang, China. [email protected].
  • # Contributed equally.
PMID: 40597639 DOI: 10.1186/s12868-025-00956-6
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.

Keywords
GBM; Shikonin; miR-361-5p.
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