ArticleOncotarget2015
ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis.Cell death discovery · 2023Article
- Decreased zinc-fingers and homeoboxes family expression was associated with unfavorable outcomes and immune infiltration in lung adenocarcinoma.Translational cancer research · 2023Article
- NFYAv1 is a Tumor-Promoting Transcript Associated with Poor Prognosis of Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Zinc Fingers and Homeobox Family in Cancer: A Double-Edged Sword.International journal of molecular sciences · 2022Review
- USP13 promotes deubiquitination of ZHX2 and tumorigenesis in kidney cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14.Cancer cell international · 2022Article
- ZHX2 in health and disease.Frontiers in oncology · 2022Review
- Article
- Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer.FEBS open bio · 2021Article
- NF-YA promotes the cell proliferation and tumorigenic properties by transcriptional activation of SOX2 in cervical cancer.Journal of cellular and molecular medicine · 2020Article
- Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake.Cell death and differentiation · 2020Article
- ZHX2 restricts hepatocellular carcinoma by suppressing stem cell-like traits through KDM2A-mediated H3K36 demethylation.EBioMedicine · 2020Article
- ZHX2 inhibits proliferation and promotes apoptosis of human lung cancer cells through targeting p38MAPK pathway.Cancer biomarkers : section A of Disease markers · 2020Article
- Discovery, characterization and potential roles of a novel NF-YAx splice variant in human neuroblastoma.Journal of experimental & clinical cancer research : CR · 2019Article
- Lobaplatin promotesCell death & disease · 2019Article
- Analysis of cyclin E co-expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer.Chronic diseases and translational medicine · 2019Article
- VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma.Science (New York, N.Y.) · 2018Article
- Hepatitis B virus X protein promotes CREB-mediated activation of miR-3188 and Notch signaling in hepatocellular carcinoma.Cell death and differentiation · 2017Article
- The Transcriptional Network Structure of a Myeloid Cell: A Computational Approach.International journal of genomics · 2017Article
- Transcription factor NF‑YA promotes a malignant phenotype by upregulating fatty acid synthase expression.Molecular medicine reports · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated suppression of liver tumor growth in vivo. Furthermore, immunohistochemical staining demonstrated the inverse correlation of ZHX2 and MDR1 expression in HCC tissues. Luciferase report assay showed that ZHX2 repressed the MDR1 promoter activity, while knockdown of NF-YA or mutating the NF-Y binding site eliminated this ZHX2-mediated repression of MDR1 transcription. Co-IP and ChIP assay further suggested that ZHX2 interacted with NF-YA and reduced NF-Y binding to the MDR1 promoter. Taken together, we clarify that ZHX2 represses NF-Y-mediated activation of MDR1 transcription and, in doing so, enhances the effects of chemotherapeutics in HCC cells both in vitro and in vivo.
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