{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:46:55Z","timestamp":1782370015936,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is a lethal malignancy requiring novel therapeutic interventions. While Polyporus umbellatus exhibits anti-tumor properties, its specific bioactive pharmacophores and molecular mechanisms remain elusive. This study integrated network pharmacology, computational simulation, and experimental validation to decipher the anti-HCC efficacy of Polyporus umbellatus. Screening identified 11 bioactive sterols, with intersection analysis revealing 63 core targets. Clinical data stratified Checkpoint Kinase 1 (CHEK1) as a critical high-risk oncogene associated with poor prognosis. Molecular dynamics simulations (100 ns) demonstrated that polyporusterone E, a key constituent, forms a thermodynamically stable complex with CHEK1 via high-affinity hydrogen bonding. In vitro assays in HepG2 and HuH-7 cells confirmed that CHEK1 overexpression drives proliferation and metastasis, while its silencing reverses these phenotypes. Crucially, treatment with Polyporus umbellatus extract and purified polyporusterone E significantly compromised HCC cell viability and downregulated CHEK1 expression at transcriptional and translational levels. These findings suggest that polyporusterone E may downregulate CHEK1 expression and modulate CHEK1-associated signaling in HCC cells, providing preliminary evidence for the molecular basis of Polyporus umbellatus and highlighting its potential as a complementary therapeutic strategy for HCC management.<\/jats:p>","DOI":"10.3390\/ijms27135694","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:16Z","timestamp":1782366496000},"page":"5694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyporusterone E, a Key Component of Polyporus umbellatus, as a Potential Regulator of CHEK 1 in Liver Cancer: Integrated Network Pharmacology, Bioinformatics, and Experimental Validation"],"prefix":"10.3390","volume":"27","author":[{"given":"Xinhui","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruichen","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinran","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150088, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Analytical Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150088, 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