ArticleCell death discovery2022
MCM2 promotes the stemness and sorafenib resistance of hepatocellular carcinoma cells via hippo signaling.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Strawberry Notch 1 Acts as a Transcriptional Regulator Driving Oncogenic Programs in Liver Carcinogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CDK4/6i reverse PARPi resistance by targeting the E2F1- MCM2/5 pathway.NPJ precision oncology · 2026Article
- GPR176 enhances the epithelial‑mesenchymal transition in gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway.Oncology reports · 2026Article
- Dissecting the Phospho-Regulatory Landscape of Protein Kinase N1 (PKN1) and Its Downstream Signaling: Functional Insights into the Activity-Dependent and Disease-Relevant Phosphosites.International journal of molecular sciences · 2026Article
- Modeling ovarian cancer chemoresistance: establishment of murine ID8 sublines and elucidation of adaptive mechanisms.Frontiers in oncology · 2026Article
- Hydrogen sulfide preserves intestinal barrier repair function through sulfhydration of RPS20 in experimental colitis.Scientific reports · 2025Article
- VPS45 Contributes to the Progression of Hepatocellular Carcinoma by Triggering the Wnt/β-Catenin Signaling Pathway.Molecular carcinogenesis · 2025Article
- Article
- CD146 regulates the stemness and chemoresistance of hepatocellular carcinoma via JAG2-NOTCH signaling.Cell death & disease · 2025Article
- SRGN-mediated reactivation of the YAP/CRISPLD2 axis promotes aggressiveness of hepatocellular carcinoma.International journal of biological sciences · 2025Article
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- Regulatory factor X-5/SCL/TAL1 interruption site axis promotes aerobic glycolysis and hepatocellular carcinoma cell stemness.The Kaohsiung journal of medical sciences · 2025Article
- Identification of Crucial Cancer Stem Cell Genes Linked to Immune Cell Infiltration and Survival in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A programmed cell death-related gene signature to predict prognosis and therapeutic responses in liver hepatocellular carcinoma.Discover oncology · 2024Article
- Regulation of cancer stem cells by CXCL1, a chemokine whose secretion is controlled by MCM2.BMC cancer · 2024Article
- Ferroptosis in liver cancer: a key role of post-translational modifications.Frontiers in immunology · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Robust analysis of a novel PANoptosis-related prognostic gene signature model for hepatocellular carcinoma immune infiltration and therapeutic response.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectA large number of studies have suggested that stemness is an essential mechanism for drug resistance, metastasis and relapse in hepatocellular carcinoma (HCC). The aim of this study was to determine the impact of MCM2 on stemness and identify potential mechanisms that complement the stemness regulatory network in HCC.
methodsMCM2 expression features and prognostic significance were analyzed in multiple cohorts, including TCGA LIHC dataset, GSE14520 dataset, Guangxi cohort, and GSE76427 dataset. Stemness-related molecules and phenotypes were examined to evaluate the impact of MCM2 on stemness. The expression levels of key molecules of the hippo signaling pathway together with downstream target genes were examined to evaluate the effect of MCM2 on hippo signaling. This was further demonstrated by rescue experiments with hippo signaling pathway inhibitors (super-TDU). Sorafenib-resistant cells were constructed to assess the effect of MCM2 on drug resistance. A xenotransplantation model of nude mice was constructed to validate the role of MCM2 in vivo.
resultsMCM2, which is expressed at higher levels in HCC tissue than in normal liver tissues, is a good indicator for distinguishing tumor tissues from normal liver tissues and can help differentiate HCC patients at different BCLC stages. The annotation of the differentially expressed genes in the MCM2 high and low expression groups indicated that MCM2 may be associated with the hippo signaling pathway. In addition, the expression of MCM2 in HCC tissues was correlated with the expression of YAP1/TAZ, which are key molecules of the hippo signaling pathway. It indicated that manipulation of MCM2 expression affects hippo signaling and stemness, while the inhibition of hippo signaling significantly reversed the effect of MCM2 on stemness. Disruption of MCM2 expression significantly elevated the sensitivity of sorafenib-resistant cells to sorafenib, as evidenced by the decrease in IC50 and diminished sphere-forming capacity. The in vivo assays showed that MCM2 effectively enhanced the efficacy of sorafenib.
conclusionMCM2 is a good prognostic marker. MCM2 enhances the stemness of HCC cells by affecting the Hippo signaling pathway, while the downregulation of MCM2 inhibits resistance towards sorafenib.
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