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<p>Uveal melanoma (UM) is among the most prevalent intraocular malignant tumors worldwide. Celastrol exhibits broad-spectrum anticancer properties; however, its underlying therapeutic mechanism in UM is yet to be elucidated. In this study, a network pharmacology approach was employed to identify potential common targets of celastrol and UM. These targets were further analyzed in conjunction with transcriptomic data and machine learning algorithms, which led to the identification of <i>CTNNB1</i> and <i>STAT3</i> as key molecular targets. The functional roles of these targets were investigated through immune infiltration analysis and single-cell RNA sequencing (scRNA-seq), while the binding stability between celastrol and CTNNB1/STAT3 was assessed using molecular docking (MD) and molecular dynamics simulation (MDS). Subsequently, celastrol was administered to B16-F10 and C918 cell lines, demonstrating that it significantly suppresses cell proliferation and migration by downregulating <i>CTNNB1</i> and <i>STAT3</i> expression, while simultaneously inducing apoptosis and cell cycle arrest. Moreover, real-time quantitative PCR (qPCR) and western blot (WB) analyses corroborated the modulation of target expression levels. Therefore, celastrol exerts potent anti-tumor effects in UM by inhibiting the CTNNB1 and STAT3 signaling pathways, thereby suppressing tumor cell proliferation and metastasis, as well as promoting cell cycle arrest and apoptosis.</p>

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Research on the molecular mechanism of celastrol targeting CTNNB1/STAT3 to inhibit uveal melanoma based on network pharmacology and multi-omics analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月24日

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  • Zhanglong Li,
  • Ruofan Xi,
  • Xudong Han,
  • Ping Zhao

摘要

Uveal melanoma (UM) is among the most prevalent intraocular malignant tumors worldwide. Celastrol exhibits broad-spectrum anticancer properties; however, its underlying therapeutic mechanism in UM is yet to be elucidated. In this study, a network pharmacology approach was employed to identify potential common targets of celastrol and UM. These targets were further analyzed in conjunction with transcriptomic data and machine learning algorithms, which led to the identification of CTNNB1 and STAT3 as key molecular targets. The functional roles of these targets were investigated through immune infiltration analysis and single-cell RNA sequencing (scRNA-seq), while the binding stability between celastrol and CTNNB1/STAT3 was assessed using molecular docking (MD) and molecular dynamics simulation (MDS). Subsequently, celastrol was administered to B16-F10 and C918 cell lines, demonstrating that it significantly suppresses cell proliferation and migration by downregulating CTNNB1 and STAT3 expression, while simultaneously inducing apoptosis and cell cycle arrest. Moreover, real-time quantitative PCR (qPCR) and western blot (WB) analyses corroborated the modulation of target expression levels. Therefore, celastrol exerts potent anti-tumor effects in UM by inhibiting the CTNNB1 and STAT3 signaling pathways, thereby suppressing tumor cell proliferation and metastasis, as well as promoting cell cycle arrest and apoptosis.