ArticleCell death & disease2017
MiRNA199a-3p suppresses tumor growth, migration, invasion and angiogenesis in hepatocellular carcinoma by targeting VEGFA, VEGFR1, VEGFR2, HGF and MMP2.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- A microRNA binding site polymorphism in the 3' UTR region of VEGF-A gene modifies colorectal cancer risk based on ethnicity: a meta-analysis.Journal of the Egyptian National Cancer Institute · 2022Pooled it
- MicroRNA Control of Hepatocyte-Stromal Crosstalk in the Early Premalignant Microenvironment of HBV-Associated HCC.International journal of molecular sciences · 2026Review
- Anticarcinogenic effects of miR-199a-loaded gold nanoparticles on hepatocellular carcinoma: in vitro study.Scientific reports · 2026Article
- Developing Potent Therapeutics for Liver Cancer Chemoresistance via an RNA Nanotech and Series-Circuit-Christmas-Bulb Mechanism Targeting ABC Transporters.Molecular pharmaceutics · 2026Review
- Suppression of exosomal miR-199a-3p, a differentially expressed miRNA in steroid-induced osteonecrosis of the femoral head, promotes cell proliferation, osteogenesis, and angiogenesis while inhibiting dexamethasone-induced apoptosis.Frontiers in bioengineering and biotechnology · 2026Article
- Article
- Targeting tumor vascular endothelial cells for hepatocellular carcinoma treatment.World journal of gastroenterology · 2025Article
- Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.Molecular cancer · 2025Review
- MicroRNA as Key Players in Hepatocellular Carcinoma: Insights into Their Role in Metastasis.Biochemical genetics · 2025Review
- Proregenerative MicroRNAs to Repair the Damaged Heart.European cardiology · 2025Review
- Exosomal crosstalk: the metastatic language of hepatocellular carcinoma.Frontiers in immunology · 2025Review
- miRNAs in HCC, pathogenesis, and targets.Hepatology (Baltimore, Md.) · 2024Article
- Review
- MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Mechanisms of Tolerance Induction in Liver Transplantation: Lessons Learned from Fetomaternal Tolerance, Autoimmunity and Tumor Immunity.International journal of molecular sciences · 2024Review
- Serum microRNA Profiles and Pathways in Hepatitis B-Associated Hepatocellular Carcinoma: A South African Study.International journal of molecular sciences · 2024Review
- miR-199a/b-3p inhibits HCC cell proliferation and invasion through a novel compensatory signaling pathway DJ-1\Ras\PI3K/AKT.Scientific reports · 2024Article
- Recent Advances in Extracellular Vesicles in Amyotrophic Lateral Sclerosis and Emergent Perspectives.Cells · 2023Review
- Identification of ferroptosis and drug resistance related hub genes to predict the prognosis in Hepatocellular Carcinoma.Scientific reports · 2023Article
- Hepatic stellate cell stearoyl co-A desaturase activates leukotriene B4 receptor 2 - β-catenin cascade to promote liver tumorigenesis.Nature communications · 2023Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing significance of tumor-stromal interaction in development and progression of cancer implies that signaling molecules in the tumor microenvironment (TME) might be the effective therapeutic targets for hepatocellular carcinoma (HCC). Here, the role of microRNA miR-199a-3p in the regulation of TME and development of HCC has been investigated by several in vitro and in vivo assays. Expression of miR-199a-3p was observed significantly low in HCC tissues and its overexpression remarkably inhibited in vivo tumor growth and metastasis to lung in NOD-SCID mice. In vitro restoration of miR-199a-3p expression either in endothelial cells (ECs) or in cancer cells (CACs) significantly diminished migration of ECs in co-culture assay. Again incubation of miR-199a-3p transfected ECs with either conditioned media (CM) of CACs or recombinant VEGF has reduced tube formation, in ECs and it was also dropped upon growth in CM of either anti-VEGF antibody-treated or miR-199a-3p-transfected CACs. In addition, bioinformatics and luciferase-reporter assays revealed that miR-199a-3p inhibited VEGF secretion from CACs and VEGFR1 and VEGFR2 expression on ECs and thus restricted cross talk between CACs and ECs. Again, restoration of miR-199a-3p in hepatic stellate cells (HSCs) reduced migration and invasion of CACs in co-culture assay, while it was enhanced by the overexpression of HGF suggesting miR-199a-3p has hindered HSC-CACs cross talk probably by inhibiting HGF and regulating matrix metalloproteinase MMP2, which were found as targets of miR-199a-3p subsequently by luciferase-reporter assay and gelatin zymography, respectively. Thus, these findings collectively highlight that miR-199a-3p restricts metastasis, invasion and angiogenesis in HCC and hence it may be considered as one of the powerful effective therapeutics for management of HCC patients.
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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.