ArticleBioengineered2021
Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression.
Article in Bioengineered, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 48 citations in OpenAlex.
- Exploring the treatment of liver cancer with Gehua Hugan Gao based on bioinformatics, network pharmacology, and molecular docking.Medicine · 2026Article
- Discovery of Bis-Thiourea Derivatives as Human DNA Topoisomerase IIα Inhibitors with Potent Anticancer Effects.ACS omega · 2026Article
- Characterization of hepatocellular carcinoma patient-derived organoids from patients receiving transarterial chemoembolization as a model for preclinical drug response assessment.Scientific reports · 2026Article
- Targeting the E2F6-TOP2A-DKK1 axis: a novel therapeutic strategy for EMT-driven hepatocellular carcinoma progression.Frontiers in immunology · 2026Article
- Mitochondrial dynamics in skin health and disease: energy, aging, and therapeutic perspectives.Burns & trauma · 2026Review
- The analysis of TOP2A as a potential target for predicting the prognosis of brain glioma in the TCGA database and in single-center study.Discover oncology · 2025Article
- Single cell-RNA sequencing reveal TOP2A as a key driver of hepatocellular carcinoma progression.Scientific reports · 2025Article
- Multi-omics analysis reveals the panoramic picture of TOP2A in pan-cancer.Scientific reports · 2025Article
- Bioinformatics screened of biomarkers for the prognosis of hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2025Article
- Advances in research on malignant tumors and targeted agents for TOP2A (Review).Molecular medicine reports · 2025Review
- Norcantharidin inhibits TOP2A expression via H3K27me3 mediated epigenetic regulation to alleviate the progression of hepatocellular carcinoma.Frontiers in pharmacology · 2025Article
- TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.Cancer biology & therapy · 2024Article
- Transiently increased coordination in gene regulation during cell phenotypic transitions.PRX life · 2024Article
- Shared and specific competing endogenous RNAs network mining in four digestive system tumors.Computational and structural biotechnology journal · 2024Article
- Expression and biological significance of topoisomerase II α (TOP2A) in oral squamous cell carcinoma.Discover oncology · 2024Article
- Identification of hub genes and pathways in hepatitis B virus-associated hepatocellular carcinoma: A comprehensive in silico study.Health science reports · 2024Article
- Immunotherapy and drug sensitivity predictive roles of a novel prognostic model in hepatocellular carcinoma.Scientific reports · 2024Article
- Knockdown of TOP2A suppresses IL-17 signaling pathway and alleviates the progression of ulcerative colitis.Immunity, inflammation and disease · 2024Article
- Article
- Alternative splicing of IRF3 plays an important role in the development of hepatocarcinoma.Epigenetics · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type IIA topoisomerase (TOP2A) is upregulated in hepatocellular carcinoma (HCC) and its expression is positively correlated with poor prognosis. However, the underlying molecular mechanism of this connection are poorly understood. Hence, the present work aimed to examine the possible mechanisms which may be useful in identifying a potential therapeutic strategy. The differential expression of TOP2A mRNA in HCC as compared with adjacent normal tissue was analyzed using the Oncomine database. The expression levels of TOP2A in HCC specimens and cell lines were assessed by Western blot and RT-qPCR. Stable cell lines were generated to knockdown or overexpress TOP2A, and then cell growth, migration, and invasion were analyzed. Furthermore, this study examined epithelial-mesenchymal transition (EMT) as well as the activation of related pathways. Additionally, the correlation between TOP2A levels and E-cadherin/Snail expression was determined in 72 HCC specimens. Higher expression levels of TOP2A were observed in HCC in Oncomine datasets, and the results were verified using 40 pairs of HCC specimens and peritumoral tissues. TOP2A expression levels were remarkably elevated in cells with great metastatic capacity. In addition, HCC cell growth, migration, and invasion were suppressed after TOP2A knockdown in MHCC97H cells (MHCC97H-shRNA-TOP2A), while these capabilities were promoted in TOP2A-overexpressing Hep3B cells (Hep3B-TOP2A). Furthermore, EMT was inhibited in MHCC97H-shRNA-TOP2A cells, but induced in Hep3B-TOP2A cells. The induction of EMT by TOP2A was shown to be mediated by Snail, as TOP2A promoted Snail expression through the p-ERK1/2/p-SMAD2 signaling pathway. TOP2A level showed a negative correlation with E-cadherin, whereas a positive correlation with that of vimentin and Snail in human HCC specimens by immunohistochemistry analyses. Kaplan-Meier survival curves revealed that TOP2A upregulation showed a positive correlation with poor prognosis patients. Taken together, TOP2A possibly enhances the metastasis of HCC by promoting EMT through the mediation of the p-ERK1/2/p-SMAD2/Snail pathway. This indicates that TOP2A maybe a potential factor to predict the prognosis of HCC.
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