ArticleEBioMedicine2020
CBX4 transcriptionally suppresses KLF6 via interaction with HDAC1 to exert oncogenic activities in clear cell renal cell carcinoma.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- In vivo CRISPR screens identify CBX4 as an epigenetic regulator for cancer immunotherapy.The Journal of clinical investigation · 2026Article
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- CBX4 facilitates EV71 replication by SUMOylation and stabilizing 3D polymerase.Frontiers in microbiology · 2026Article
- Lactylation in kidney diseases: a review of regulatory mechanisms and therapeutic prospects.Frontiers in cell and developmental biology · 2026Review
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- ABRACL upregulated by transcription factor CBX4 promotes proliferation and migration and inhibits the apoptosis of gastric cancer cells.Histology and histopathology · 2025Article
- Integrated bioinformatics investigation and experimental validation reveals the clinical and biological significance of chromobox family in breast cancer.Scientific reports · 2025Article
- High-throughput methylation sequencing reveals novel biomarkers for the early detection of renal cell carcinoma.BMC cancer · 2025Article
- CBX4 Drives Gastric Cancer Progression by ActivatingOncology research · 2025Article
- Role and mechanism of the CBX4-HDAC5-CERS6 axis in disrupting sphingomyelin metabolism in acute myeloid leukemia.American journal of cancer research · 2025Article
- Formononetin suppresses the malignant progression of papillary thyroid carcinoma depending on downregulation of CBX4.Experimental and therapeutic medicine · 2024Article
- Development and verification of a novel risk model related to ubiquitination linked with prognosis and therapeutic response in clear cell renal cell carcinoma.Scientific reports · 2024Article
- Multicohort Epigenome-Wide Association Study of All-Cause Cardiovascular Disease and Cancer Incidence: A Cardio-Oncology Approach.JACC. CardioOncology · 2024Article
- CBX4 plays a bidirectional role in transcriptional regulation and lung adenocarcinoma progression.Cell death & disease · 2024Article
- Set7/9 aggravates ischemic brain injury via enhancing glutamine metabolism in a blocking Sirt5 manner.Cell death and differentiation · 2024Article
- CBX4 promotes antitumor immunity by suppressing Pdcd1 expression in T cells.Molecular oncology · 2023Article
- RING finger gene 180 inhibits osteosarcoma progression through regulating chromobox homolog 4 ubiquitination.Cell cycle (Georgetown, Tex.) · 2023Article
- Comprehensive bioinformatics analysis of the expression, prognostic value, and immune infiltration of chromobox family members in cervical cancer.Iranian journal of basic medical sciences · 2023Article
- Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review).International journal of oncology · 2023Review
- Combining expression of RNF43 and infiltration level of CD163Cancer medicine · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDysregulation of polycomb chromobox (CBX) proteins that mediate epigenetic gene silencing contributes to the progression of human cancers. Yet their roles in clear cell renal cell carcinoma (ccRCC) remain to be explored.
methodsThe expression of CBX4 and its clinical significance were determined by qRT-PCR, western blot, immunohistochemistry and statistical analyses. The biological function of CBX4 in ccRCC tumor growth and metastasis and the underlying mechanism were investigated using in vitro and in vivo models.
findingsCBX4 exerts oncogenic activities in ccRCC via interaction with HDAC1 to transcriptionally suppress tumor suppressor KLF6. CBX4 expression is increased in ccRCC and correlated with poor prognosis in two independent cohorts containing 840 patients. High CBX4 expression is significantly associated with Fuhrman grade and tumor lymph node invasion. CBX4 overexpression promotes tumor growth and metastasis, whereas CBX4 knockdown results in the opposite phenotypes. Mechanistically, CBX4 downregulates KLF6 via repressing the transcriptional activity of its promoter. Further studies show that CBX4 physically binds to HDAC1 to maintain its localization on the KLF6 promoter. Ectopic expression of KLF6 or disruption of CBX4-HDAC1 interaction attenuates CBX4-mediated cell growth and migration. Furthermore, CBX4 depletion markedly enhances the histone deacetylase inhibitor (HDACi)-induced cell apoptosis and suppression of tumor growth.
interpretationOur data suggest CBX4 as an oncogene with prognostic potential in ccRCC. The newly identified CBX4/HDAC1/KLF6 axis may represent a potential therapeutic target for the clinical intervention of ccRCC.
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