GINS1 Induced Sorafenib Resistance by Promoting Cancer Stem Properties in Human Hepatocellular Cancer Cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34414190", "kind": "science-record", "revision": 7, "content_hash": "sha256:f3e30b973a7c15d511a133eb51834c9da87d67b8addd157e0072299f1b456d85", "created_at": "2026-11-01T15:41:48Z", "updated_at": "2026-11-01T22:04:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "GINS1 Induced Sorafenib Resistance by Promoting Cancer Stem Properties in Human Hepatocellular Cancer Cells.", "doi": "10.3389/fcell.2021.711894", "pmid": "34414190", "authors": ["Sheng Li", "Lina Wu", "Hong Zhang", "Xijuan Liu", "Zilei Wang", "Bin Dong", "Guang Cao"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Hepatocellular carcinoma (HCC) is characterized by a high rate of incidence and recurrence, and resistance to chemotherapy may aggravate the poor prognosis of HCC patients. Sorafenib resistance is a conundrum to the treatment of advanced/recurrent HCC. Therefore, studies on the molecular pathogenesis of HCC and the resistance to sorafenib are of great interest. Here, we report that GINS1 was highly expressed in HCC tumors, associated with tumor grades, and predicted poor patient survival using Gene Expression Omnibus (GEO) databases exploration. Cell cycle, cell proliferation assay and in vivo xenograft mouse model indicated that knocking down GINS1 induced in G1/S phase cell cycle arrest and decreased tumor cells proliferation in vitro and in vivo. Spheroid formation assay results showed that GINS1 promoted the stem cell activity of HCC tumor cells. Furthermore, GEO database (GSE17112) analysis showed that HRAS oncogenic gene set was enriched in GINS1 high-expressed cancer cells, and quantitative real-time PCR, and Western blot results proved that GINS1 enhanced HCC progression through regulating HRAS signaling pathway. Moreover, knocking down endogenous GINS1 with shGINS1 increased the sensitivity of HCC cells to sorafenib, and restoring HRAS or stem associated pathway partly recovered the sorafenib resistance. Overall, the collective findings highlight GINS1 functions in hepatocarcinogenesis and sorafenib resistance, and indicate its potential use of GINS1 in drug-resistant HCC.", "claims": [{"id": "claim-method", "statement": "Overall survival curves were plotted according to the Kaplan–Meier method and the generalized log-rank test was applied to analyze the survival curves.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34414190", "locator": "sections[13] \"Statistical Analysis\" paragraph 2", "quote": "Overall survival curves were plotted according to the Kaplan–Meier method and the generalized log-rank test was applied to analyze the survival curves."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34414190", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author/s."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34414190"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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