Ligusticum chuanxiong Hort. Targets hsa-miR-10a-5p to Potentially Induce Apoptosis and Modulate Lipid Metabolism in Glioblastoma: A Natural-Product-Based Therapeutic Strategy

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Publicado en:Pharmaceuticals vol. 18, no. 10 (2025), p. 1553-1579
Autor principal: Xiao-Xuan, Cai
Otros Autores: Hua-Li, Zuo, Li, Jing, Hsi-Yuan, Huang, Li-Ping, Li, Ni Jie, Pei-Sen, Wu, Xiao-Yuan, Xu, Zhang, Dan, Yue-Yang, Xie, Huang Hsien-Da, Yang-Chi-Dung, Lin
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100 1 |a Xiao-Xuan, Cai  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
245 1 |a <i>Ligusticum chuanxiong</i> Hort. Targets hsa-miR-10a-5p to Potentially Induce Apoptosis and Modulate Lipid Metabolism in Glioblastoma: A Natural-Product-Based Therapeutic Strategy 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a Background/Objectives: Glioblastoma (GBM), the most aggressive primary malignant brain tumor, has a dismal prognosis and limited treatment options. The dried rhizome of Ligusticum chuanxiong Hort. (Chuanxiong, CX) is a traditional Chinese medicinal herb frequently prescribed in formulas intended to invigorate blood circulation. CX also exhibits anti-glioma activity, but its molecular mechanisms remain incompletely understood. Methods: In this study, we combined transcriptomics and Raman spectroscopy to investigate the effects of reconstituted CX-dispensing granules (hereafter referred to as CXG solution) on U87MG cells, suggesting their dual role in promoting cell death and modulating collagen deposition and lipid metabolism. Results: Mechanistically, we demonstrated that the CXG solution downregulates hsa-miR-10a-5p, which directly targets BCL2L11, known to induce pro-apoptotic effects, as validated by qPCR and dual-luciferase reporter assays. Furthermore, the CXG solution and hsa-miR-10a-5p suppress lipid metabolism through a coherent feed-forward loop via targeting transcription factors SREBF1 and E2F1. An electrophoretic mobility shift assay (EMSA) confirmed E2F1 binds to the hsa-miR-29a promoter, leading to the synergistic repression of hsa-miR-29a-3p by SREBF1 and E2F1. Network pharmacology analysis combined with molecular docking suggested that the ferulic acid and adenosine in CX potentially modulate EGFR-the E2F1-hsa-miR-10a-5p axis. Conclusions: These findings elucidate CX’s multi-target anti-GBM mechanisms and propose a novel therapeutic strategy combining metabolic intervention with miRNA-targeted therapy, providing novel insights into feed-forward loop regulation in miRNA networks. 
653 |a Medical prognosis 
653 |a Metastasis 
653 |a Collagen 
653 |a Spectrum analysis 
653 |a Glioma 
653 |a Traditional Chinese medicine 
653 |a Extracellular matrix 
653 |a MicroRNAs 
653 |a Metabolism 
653 |a Lipids 
653 |a Genes 
653 |a Apoptosis 
653 |a Cell growth 
653 |a Metabolites 
653 |a Morphology 
653 |a Survival analysis 
653 |a Chemotherapy 
653 |a Drug dosages 
700 1 |a Hua-Li, Zuo  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Li, Jing  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Hsi-Yuan, Huang  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Li-Ping, Li  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Ni Jie  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Pei-Sen, Wu  |u School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; peisenwu@link.cuhk.edu.cn (P.-S.W.); xiaoyuanxu@link.cuhk.edu.cn (X.-Y.X.) 
700 1 |a Xiao-Yuan, Xu  |u School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; peisenwu@link.cuhk.edu.cn (P.-S.W.); xiaoyuanxu@link.cuhk.edu.cn (X.-Y.X.) 
700 1 |a Zhang, Dan  |u Longgang Central Hospital of Shenzhen, Shenzhen 518116, China; 13762470784@163.com 
700 1 |a Yue-Yang, Xie  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Huang Hsien-Da  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
700 1 |a Yang-Chi-Dung, Lin  |u Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China; xiaoxuancai@link.cuhk.edu.cn (X.-X.C.); zuohuali@cuhk.edu.cn (H.-L.Z.); lijing0903@cuhk.edu.cn (J.L.); huanghsiyuan@cuhk.edu.cn (H.-Y.H.); liliping@cuhk.edu.cn (L.-P.L.); jennyni@cuhk.edu.cn (J.N.); yueyangxie@link.cuhk.edu.cn (Y.-Y.X.) 
773 0 |t Pharmaceuticals  |g vol. 18, no. 10 (2025), p. 1553-1579 
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