ArticleClinical epigenetics2019
The E3 ubiquitin ligase RNF40 suppresses apoptosis in colorectal cancer cells.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.Human genomics · 2019Pooled it
- Mutant KRAS-mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- E3 ubiquitin ligase RNF40: Structure, function and its context‑dependent roles in tumorigenesis (Review).Oncology reports · 2026Review
- Decoding RNF20: an epigenetic modifier and beyond.Frontiers in cell and developmental biology · 2026Review
- Twist1 silencing suppresses triple-negative breast cancer progression by reducing RNF40 transcription.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- RNF20/RNF40 supports the aggressive behavior in cervical cancer by regulating a peroxisome-based anti-ferroptotic mechanism.Cell communication and signaling : CCS · 2025Article
- Epigenome-wide analysis reveals potential biomarkers for radiation-induced toxicity risk in prostate cancer.Clinical epigenetics · 2025Article
- Rnf40 Exacerbates Hypertension-Induced Cerebrovascular Endothelial Barrier Dysfunction by Ubiquitination and Degradation of Parkin.CNS neuroscience & therapeutics · 2025Article
- Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20.British journal of cancer · 2024Article
- The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.Cell death discovery · 2023Review
- RNF40 epigenetically modulates glycolysis to support the aggressiveness of basal-like breast cancer.Cell death & disease · 2023Article
- A bibliometric of research trends in acupuncture for spinal cord injury: Quantitative and qualitative analyses.Frontiers in neurology · 2022Article
- A joint analysis using exome and transcriptome data identifiescandidate polymorphisms and genes involved with umbilical hernia in pigs.BMC genomics · 2021Article
- Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.International journal of molecular sciences · 2021Review
- RNF20 and RNF40 regulate vitamin D receptor-dependent signaling in inflammatory bowel disease.Cell death and differentiation · 2021Article
- USP22 SuppressesCancers · 2021Article
- RNF40 exerts stage-dependent functions in differentiating osteoblasts and is essential for bone cell crosstalk.Cell death and differentiation · 2021Article
- Epigenetic modification and a role for the E3 ligase RNF40 in cancer development and metastasis.Oncogene · 2021Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide, and deciphering underlying molecular mechanism is essential. The loss of monoubiquitinated histone H2B (H2Bub1) was correlated with poor prognosis of CRC patients and, accordingly, H2Bub1 was suggested as a tumor-suppressive mark. Surprisingly, our previous work revealed that the H2B ubiquitin ligase RING finger protein 40 (RNF40) might exert tumor-promoting functions. Here, we investigated the effect of RNF40 loss on tumorigenic features of CRC cells and their survival in vitro.
methodsWe evaluated the effects of RNF40 depletion in several human CRC cell lines in vitro. To evaluate cell cycle progression, cells were stained with propidium iodide and analyzed by flow cytometry. In addition, to assess apoptosis rates, caspase 3/7 activity was assessed in a Celigo® S-based measurement and, additionally, an Annexin V assay was performed. Genomic occupancy of H2Bub1, H3K79me3, and H3K27ac was determined by chromatin immunoprecipitation. Transcriptome-wide effects of RNF40 loss were evaluated based on mRNA-seq results, qRT-PCR, and Western blot. To rescue apoptosis-related effects, cells were treated with Z-VAD-FMK.
resultsHuman CRC cell lines displayed decreased cell numbers in vitro after RNF40 depletion. While the differences in confluence were not mediated by changes in cell cycle progression, we discovered highly increased apoptosis rates after RNF40 knockdown due to elevated caspase 3/7 activity. This effect can be explained by reduced mRNA levels of anti-apoptotic and upregulation of pro-apoptotic BCL2 family members. Moreover, the direct occupancy of the RNF40-mediated H2B monoubiquitination was observed in the transcribed region of anti-apoptotic genes. Caspase inhibition by Z-VAD-FMK treatment rescued apoptosis in RNF40-depleted cells. However, knockdown cells still displayed decreased tumorigenic features despite the absence of apoptosis.
conclusionsOur findings reveal that RNF40 is essential for maintaining tumorigenic features of CRC cells in vitro by controlling the expression of genes encoding central apoptotic regulators.
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