ArticleThe Journal of clinical investigation2021
SUMOylation promotes extracellular vesicle-mediated transmission of lncRNA ELNAT1 and lymph node metastasis in bladder cancer.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 101 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
101 citing papers in PubMed, 3 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Exosomal noncoding RNAs as noninvasive biomarkers in bladder cancer: a diagnostic meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Pooled it
- Diagnostic and prognostic potential of exosome non-coding RNAs in bladder cancer: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Exosome-Derived Long Non-Coding RNAs as Non-Invasive Biomarkers of Bladder Cancer.Frontiers in oncology · 2021Pooled it
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- MVB Maturation Responsive to KRASJournal of extracellular vesicles · 2026Article
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Small Extracellular Vesicles in Cardioprotection, Cardiac Repair, and Regeneration: Cargo Mechanisms, Producer Cell Sources, and Translational Development.Biomedicines · 2026Review
- Extracellular vesicle-mediated GALNT1/RPRD1A glycosylation axis drives immune escape and peritoneal metastasis in gastric cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Small Extracellular Vesicle-TLN1 Modulates Gastric Cancer Cells and Remodels Lymphatic Endothelial Cells Through AKT Activation to Potentiate Lymphatic Metastasis.Cell biology international · 2026Article
- Exosome-mimetic nanocarriers in cancer diagnosis and drug delivery: engineering strategies, functional biomimicry, safety considerations, and clinical translation.Journal of nanobiotechnology · 2026Review
- Ubc9-mediated SUMOylation of Ninj1 alleviates inflammatory responses in hepatic ischaemia/reperfusion injury.Clinical and translational medicine · 2026Article
- Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application.Journal of advanced research · 2026Review
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Review
- LncRNA miR17HG promotes tumor progression through AXIN2 by sponging miR-144-3p in bladder cancer.World journal of surgical oncology · 2026Article
- Lactylation-drived TRIM29 induces invasive behavior and lymph node metastasis in gastric cancer via hnRNPA1-mediated Wnt/β-catenin pathway.Cell death & disease · 2026Article
- Long non-coding RNAs in the exosomal network: dual roles and clinical implications in cancer.Animal cells and systems · 2026Review
- Significance of EVs in Prostate Cancer Bone Metastases.International journal of molecular sciences · 2025Review
- SNHG16 promotes breast cancer progression by regulating the hsa-let-7b-5p/AURKA axis.Biochemistry and biophysics reports · 2025Article
- Extracellular vesicles-derived LncRNA MAFG-AS1 predicts clinical response to pembrolizumab in patients with advanced urothelial carcinoma.Molecular biology reports · 2025Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byUro-Science.2021
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small ubiquitin-like modifier (SUMO) binding (termed SUMOylation) emerged as the inducer for the sorting of bioactive molecules into extracellular vesicles (EVs), triggering lymphangiogenesis and further driving tumor lymph node (LN) metastasis, but the precise mechanisms remain largely unclear. Here, we show that bladder cancer (BCa) cell-secreted EVs mediated intercellular communication with human lymphatic endothelial cells (HLECs) through transmission of the long noncoding RNA ELNAT1 and promoted lymphangiogenesis and LN metastasis in a SUMOylation-dependent manner in both cultured BCa cell lines and mouse models. Mechanistically, ELNAT1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1 at the lysine 113 residue, which mediated recognition of ELNAT1 by the endosomal sorting complex required for transport (ESCRT) and facilitated its packaging into EVs. EV-mediated ELNAT1 was specifically transmitted into HLECs and epigenetically activated SOX18 transcription to induce lymphangiogenesis. Importantly, blocking the SUMOylation of tumor cells by downregulating UBC9 expression markedly reduced lymphatic metastasis in EV-mediated, ELNAT1-treated BCa in vivo. Clinically, EV-mediated ELNAT1 was correlated with LN metastasis and a poor prognosis for patients with BCa. These findings highlight a molecular mechanism whereby the EV-mediated ELNAT1/UBC9/SOX18 regulatory axis promotes lymphangiogenesis and LN metastasis in BCa in a SUMOylation-dependent manner and implicate ELNAT1 as an attractive therapeutic target for LN metastatic BCa.
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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.