ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1580704
Shikonin as a therapeutic agent in renal cell carcinoma: insights from TEK-related causal association with glaucoma
Provisionally accepted
- 1Department of Urology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, China, Jinan, China
- 2Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China
- 3Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life science, Shandong University, Qingdao, Shandong Province, China
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Renal cell carcinoma (RCC) is a lethal malignancy with rising incidence and incompletely understood pathogenesis. Emerging evidence suggests potential systemic links between RCC and glaucoma, a chronic ocular disease. Using two‐step Mendelian randomization across the NHGRI-EBI GWAS Catalog and FinnGen databases, we identified a significant causal association between glaucoma and RCC, further supported by observational data from NHANES. Gene expression analysis revealed that glaucoma-associated genes, particularly TEK, were dysregulated in RCC tissues and associated with key clinical features. Functional experiments demonstrated that the natural compounds shikonin and acetylshikonin upregulate TEK expression and effectively inhibit RCC cell proliferation and migration by suppressing AKT/mTOR signaling pathway. Collectively, these findings support a role for glaucoma-associated genes in RCC development and progression, highlighting shikonin as a promising therapeutic agent targeting this molecular axis.
Keywords: Gene Expression, Glaucoma, Mendelian Randomization (MR), NHANES, Renal cell carcinoma (RCC), Shikonin, TEK
Received: 14 Mar 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Jia, Liang, Benkui, Li, Chen, Zhang, Bian and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Renbo Guo, Department of Urology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, China, Jinan, China
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