Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27738335", "kind": "science-record", "revision": 9, "content_hash": "sha256:3b849a4da432520a5dca213dc722acf133a745b7fa4b20cb0b4fc3c25e193adf", "created_at": "2026-11-01T15:40:20Z", "updated_at": "2026-11-01T22:42:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Waltonitone inhibits proliferation of hepatoma cells and tumorigenesis via FXR-miR-22-CCNA2 signaling pathway.", "doi": "10.18632/oncotarget.12614", "pmid": "27738335", "authors": ["Fan Yang", "Junting Gong", "Guangyun Wang", "Peng Chen", "Li Yang", "Zhengtao Wang"], "journal": "Oncotarget", "year": 2016, "abstract": "Waltonitone (WA), an ursane-type pentacyclic triterpene extracted from Gentiana waltonii Burkill, was recently appeared to exert anti-tumor effect. However, the biological underpinnings underlying the role of WA in hepatocellular carcinoma (HCC) cells have not been completely elucidated. Our previous report indicated that the FXR-regulated miR-22-CCNA2 pathway contributed to the progression and development of HCC. Besides, a wide spectrum of microRNAs (miRNAs) could be up- or down-regulated upon WA treatment, including miR-22. Hence, we aimed to determine whether WA inhibited HCC cell proliferation via the FXR-miR-22-CCNA2 axis. In this study, we observed a significant downregulation of FXR and miR-22, along with upregulation of CCNA2 in 80 paired tumors relative to adjacent normal tissues of HCC subjects, which were obtained from the available GEO database in NCBI (GSE22058). Furthermore, we validated the expression patterns of these three targets in another set of HCC samples and found the highly correlation within each other. Additionally, our data demonstrated that WA induced miR-22 and repressed CCNA2 in HCC cells, which contributed to the cell proliferation arrest. In addition, evidence suggested that either miR-22 silencing or FXR knockdown reversed the diminished CCNA2 expression as well as cell proliferation inhibition caused by WA treatment and WA inhibited tumor masses in vivo in a subcutaneous xenograft mouse model of HCC. Overall, our data indicated that WA inhibited HCC cell proliferation and tumorigenesis through miR-22-regulated CCNA2 repression, which was at least partially through FXR modulation.", "claims": [{"id": "claim-method", "statement": "One-way ANOVA and T-test statistics were performed using SPSS 20.0 (SPSS Inc. Chicago, IL, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27738335", "locator": "sections[23] \"Data analysis\" paragraph 2", "quote": "One-way ANOVA and T-test statistics were performed using SPSS 20.0 (SPSS Inc. 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The downloaded series matrix files contain miRNA and mRNA data, and the relative expression levels of FXR, miR-22 and CCNA2 were selected for correlation analysis."}], "state": "complete"}, {"id": "claim-target-result", "statement": "WA inhibited HCC cell proliferation and tumorigenesis through miR-22-regulated CCNA2 repression, at least partially through FXR modulation. The statistical methods were one-way ANOVA and t-test analyses performed with SPSS 20.0. The clinical expression data were downloaded from the NCBI GEO database (GSE22058), and tissue samples were obtained from the Translational Pathology Core Laboratory at the University of California, Los Angeles; cell RNA was extracted with TRIzol and reverse-transcribed before quantification by real-time PCR.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27738335", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Overall, our data indicated that WA inhibited HCC cell proliferation and tumorigenesis through miR-22-regulated CCNA2 repression, which was at least partially through FXR modulation."}, {"asset": "source:pmid:27738335", "locator": "sections[23] \"Data analysis\" paragraph 2", "quote": "One-way ANOVA and T-test statistics were performed using SPSS 20.0 (SPSS Inc. 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The statistical methods were one-way ANOVA and t-test analyses performed with SPSS 20.0. 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