ArticleCancer medicine2020
ZHX2 mediates proteasome inhibitor resistance via regulating nuclear translocation of NF-κB in multiple myeloma.
Article in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors.Cell communication and signaling : CCS · 2024Review
- Cooperative regulation of Zhx1 and hnRNPA1 drives the cardiac progenitor-specific transcriptional activation during cardiomyocyte differentiation.Cell death discovery · 2023Article
- Fabrication of polycaprolactone electrospun fibres with retinyl acetate for antioxidant delivery in a ROS-mimicking environment.Frontiers in bioengineering and biotechnology · 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 in health and disease.Frontiers in oncology · 2022Review
- Review
- ZHX2 mediates proteasome inhibitor resistance via regulating nuclear translocation of NF-κB in multiple myeloma.Cancer medicine · 2020Article
- Application of urine immunofixation electrophoresis in prognostic evaluation of hematopoietic stem cell transplantation in patients with myeloma.Pakistan journal of medical sciencesArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple myeloma (MM) is an incurable hematological malignancy. Although proteasome inhibitors and immunomodulators have significantly improved patient outcomes, some patients respond poorly to treatment and almost all patients will relapse. Mechanisms of proteasome inhibitor resistance in multiple myeloma have not been fully elucidated. ZHX2 is a transcription regulator degraded via proteasome and presents both oncogenic or tumor suppressive effect in different cancers, however, it is still unknown that the role of ZHX2 in myeloma. In this study, we aim to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM.
methodsGSE24080 gene expression profile datasets from Gene Expression Omnibus (GEO) were analyzed to evaluate the relationship between ZHX2 expression level and survival in MM. Expression of ZHX2 in human MM cell lines at baseline and after bortezomib (BTZ) treatment was determined by Western blotting (WB). The proliferation and apoptosis rate of MM cells treated with BTZ after the knockdown of ZHX2 were analyzed by flow cytometry. Nuclear translocation of NF-κB after the knockdown of ZHX2 was evaluated by WB and immunofluorescence, and the expression of NF-κB target genes was measured by real-time quantitative PCR. Co-immunoprecipitation (Co-IP) and WB were used to detect the interaction of ZHX2 with NF-κB.
resultsWe found that higher ZHX2 expression was correlated with poorer clinical outcomes of patients. In addition, ZHX2 expression was relatively higher in RPMI-8226 and MM.1S cell lines and the level of ZHX2 protein was upregulated after BTZ treatment. Knockdown of ZHX2 significantly enhanced the sensitivity of MM cells to BTZ, inhibited nuclear translocation of NF-κB, and reduced mRNA expression of NF-κB target genes. It was also revealed that ZHX2 directly binds to NF-κB.
conclusionOur study showed that ZHX2 can promote proteasome inhibitor resistance in MM cells by regulating the nuclear translocation of NF-κB.
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