ArticleOncogene2019
Cervical squamous cell carcinoma-secreted exosomal miR-221-3p promotes lymphangiogenesis and lymphatic metastasis by targeting VASH1.
Article in Oncogene, 2019. 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 146 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.
- Applications of Exosomes in Female Medicine: A Systematic Review of Molecular Biology, Diagnostic and Therapeutic Perspectives.International journal of molecular sciences · 2026Pooled it
- Small extracellular vesicle-mediated transfer of HPV16 transcripts from Ca Ski cells increases proliferation of HPV-negative recipient cancer cells.Cell communication and signaling : CCS · 2026Article
- The prognostic value of miR-127-5p in cervical squamous cell carcinoma and its role in suppressing malignant behavior of cancer cells via SNX10 inhibition.Discover oncology · 2026Article
- Association of Porphyromonas gingivalis-infected oral squamous cell carcinoma cell-secreted exosomal miR-3648-1-p5 with tumor progression.Cancer cell international · 2026Article
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- The avatar principle: exosomal dynamics guiding tumor adaptation and next-generation therapeutic strategies.Journal of nanobiotechnology · 2026Review
- Advances in exosomal non-coding RNAs in cervical cancer (Review).Molecular and clinical oncology · 2025Review
- Exosomal miR-122-5p for regulation of secretory functions of fibroblasts and promotion of breast cancer metastasis by targeting MKP-2: an experimental study.Cancer biology & therapy · 2025Article
- Analysis of research hotspots on the detection of vascular endothelial growth factor C and its receptor vascular endothelial growth factor receptor-3 in cervical squamous cell carcinoma.Discover oncology · 2025Article
- New insights into extracellular vesicles in metastatic cancer: From mechanisms to diagnostics and targeted therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Bibliometric analysis of research on cervical cancer and miRNAs from 2010 to 2024: research trends, hotspots, and prospects.Discover oncology · 2025Article
- Extracellular vesicle-mediated transmission of circPDLIM5 promotes lymphatic metastasis in prostate cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice.Chinese medicine · 2025Article
- Exosome-based approaches in cancer along with unlocking new insights into regeneration of cancer-prone tissues.Regenerative therapy · 2025Review
- The Pre-metastatic Niche: How Cancer Stem Cell-Derived Exosomal MicroRNA Fit into the Puzzle.Stem cell reviews and reports · 2025Review
- Emerging roles of exosomal circRNAs in non-small cell lung cancer.Journal of translational medicine · 2025Review
- Small molecule inhibitors of hnRNPA2B1-RNA interactions reveal a predictable sorting of RNA subsets into extracellular vesicles.Nucleic acids research · 2025Article
- Comparative microRNA signatures based on liquid biopsy to identify lymph node metastasis in T1 colorectal cancer patients undergoing upfront surgery or endoscopic resection.Cell death discovery · 2025Article
- Exosomal miR-224-3p promotes lymphangiogenesis and lymph node metastasis by targeting GSK3B in gastric cancer.Oncology research · 2025Article
- Exosomal ncRNAs in liquid biopsy: a new paradigm for early cancer diagnosis and monitoring.Frontiers in oncology · 2025Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Cancer-secreted exosomal miRNAs are emerging mediators of cancer-stromal cross-talk in the tumor environment. Our previous miRNAs array of cervical squamous cell carcinoma (CSCC) clinical specimens identified upregulation of miR-221-3p. Here, we show that miR-221-3p is closely correlated with peritumoral lymphangiogenesis and lymph node (LN) metastasis in CSCC. More importantly, miR-221-3p is characteristically enriched in and transferred by CSCC-secreted exosomes into human lymphatic endothelial cells (HLECs) to promote HLECs migration and tube formation in vitro, and facilitate lymphangiogenesis and LN metastasis in vivo according to both gain-of-function and loss-of-function experiments. Furthermore, we identify vasohibin-1 (VASH1) as a novel direct target of miR-221-3p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of VASH1 could respectively rescue and simulate the effects induced by exosomal miR-221-3p. Importantly, the miR-221-3p-VASH1 axis activates the ERK/AKT pathway in HLECs independent of VEGF-C. Finally, circulating exosomal miR-221-3p levels also have biological function in promoting HLECs sprouting in vitro and are closely associated with tumor miR-221-3p expression, lymphatic VASH1 expression, lymphangiogenesis, and LN metastasis in CSCC patients. In conclusion, CSCC-secreted exosomal miR-221-3p transfers into HLECs to promote lymphangiogenesis and lymphatic metastasis via downregulation of VASH1 and may represent a novel diagnostic biomarker and therapeutic target for metastatic CSCC patients in early stages.
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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.