ArticleCell death & disease2022
RNF4~RGMb~BMP6 axis required for osteogenic differentiation and cancer cell survival.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed.
- Article
- ZNF468 stabilization by RNF4 enhances apoptosis resistance and carboplatin resistance in breast cancer via transcription activation of XIAP.Genes & genomics · 2026Article
- Genomic structural equation modeling reveals the shared genetic architecture of osteosarcopenia across five musculoskeletal phenotypes.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Multi-omics Mendelian randomization prioritizes BMP6 as a candidate therapeutic target in intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2026Article
- Bone Morphogenetic Protein 6 Attenuates Psoriasis Pathogenesis by Suppressing Th17 Cell Differentiation.Inflammation · 2026Article
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Tracing the stemness and malignant transition in a heritable colorectal cancer Lynch Syndrome by single-cell RNA-seq analysis.Frontiers in immunology · 2026Article
- Single-nucleus transcriptomics decodes the link between aging and lumbar disc herniation.Protein & cell · 2025Article
- BMP6 ubiquitination mediated by SMURF1 suppresses ferroptosis and diminishes sensitivity to doxorubicin in gastric cancer.Gastroenterology report · 2025Article
- Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.Cancer biology & medicine · 2024Review
- Repulsive guidance molecules b (RGMb): molecular mechanism, function and role in diseases.Expert reviews in molecular medicine · 2024Review
- DARPins detect the formation of hetero-tetramers of p63 and p73 in epithelial tissues and in squamous cell carcinoma.Cell death & disease · 2023Article
- USP28 controls SREBP2 and the mevalonate pathway to drive tumour growth in squamous cancer.Cell death and differentiation · 2023Article
- IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.BMC oral health · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular understanding of osteogenic differentiation (OD) of human bone marrow-derived mesenchymal stem cells (hBMSCs) is important for regenerative medicine and has direct implications for cancer. We report that the RNF4 ubiquitin ligase is essential for OD of hBMSCs, and that RNF4-deficient hBMSCs remain as stalled progenitors. Remarkably, incubation of RNF4-deficient hBMSCs in conditioned media of differentiating hBMSCs restored OD. Transcriptional analysis of RNF4-dependent gene signatures identified two secreted factors that act downstream of RNF4 promoting OD: (1) BMP6 and (2) the BMP6 co-receptor, RGMb (Dragon). Indeed, knockdown of either RGMb or BMP6 in hBMSCs halted OD, while only the combined co-addition of purified RGMb and BMP6 proteins to RNF4-deficient hBMSCs fully restored OD. Moreover, we found that the RNF4-RGMb-BMP6 axis is essential for survival and tumorigenicity of osteosarcoma and therapy-resistant melanoma cells. Importantly, patient-derived sarcomas such as osteosarcoma, Ewing sarcoma, liposarcomas, and leiomyosarcomas exhibit high levels of RNF4 and BMP6, which are associated with reduced patient survival. Overall, we discovered that the RNF4~BMP6~RGMb axis is required for both OD and tumorigenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.