ArticleScientific reports2013
The brain microenvironment negatively regulates miRNA-768-3p to promote K-ras expression and lung cancer metastasis.
Article in Scientific reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Exploration of patient plasma exosomes as biomarkers for predicting lung cancer brain metastasis.Frontiers in medicine · 2025Article
- MicroRNAs in Lung Cancer Brain Metastasis.International journal of molecular sciences · 2024Review
- MiRNAs as new potential biomarkers and therapeutic targets in brain metastasis.Non-coding RNA research · 2024Review
- The Role of Exosome-Derived microRNA on Lung Cancer Metastasis Progression.Biomolecules · 2023Review
- Cell-Free miRNAs as Non-Invasive Biomarkers in Brain Tumors.Diagnostics (Basel, Switzerland) · 2023Review
- Review
- Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.Frontiers in immunology · 2023Review
- Molecular Biology of Brain Metastases.Brain tumor research and treatment · 2023Review
- Small Nucleolar Derived RNAs as Regulators of Human Cancer.Biomedicines · 2022Review
- Review
- Emerging role of non-coding RNAs in the regulation of KRAS.Cancer cell international · 2022Review
- Microenvironmental Variations After Blood-Brain Barrier Breakdown in Traumatic Brain Injury.Frontiers in molecular neuroscience · 2021Review
- MicroRNA signature of central nervous system-infiltrating dendritic cells in an animal model of multiple sclerosis.Immunology · 2018Article
- Potential Molecular Signatures Predictive of Lung Cancer Brain Metastasis.Frontiers in oncology · 2018Review
- Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options.Cellular oncology (Dordrecht, Netherlands) · 2017Review
- Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma.Molecular cancer · 2017Review
- Targeting NRASAmerican journal of cancer research · 2017Article
- rs15869 at miRNA binding site in BRCA2 is associated with breast cancer susceptibility.Medical oncology (Northwood, London, England) · 2016Article
- RAS-MAPK pathway epigenetic activation in cancer: miRNAs in action.Oncotarget · 2016Review
- MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment.Oncogene · 2015Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The brain microenvironment promotes metastasis through mechanisms that remain elusive. Co-culture of lung cancer cells with astrocytes - the most abundant cell type within the metastatic brain niche - lead to downregulation of miRNA-768-3p which drives K-ras expression and key signaling pathways, enhances cell viability and promotes chemotherapeutic resistance. Vector-based forced expression of miRNA-768-3p complementary sequence or a chemically-engineered miRNA-768-3p inhibitor recapitulated the astrocyte effect to increase tumor cell viability. The miRNA-768-3p inhibitor targeted the K-ras 3'-UTR as demonstrated by increased luminescence from a luciferase reporter and strikingly increased the K-ras protein and the downstream effectors ERK1/2 and B-Raf. miRNA-768-3p was reduced in patient brain metastases compared to normal brain tissue and was lower in patient tissue from brain metastases compared to same-patient primary tumour tissue. The brain microenvironment negatively regulates miRNA-768-3p to enhance K-ras and promote metastasis. We propose that therapeutic replacement of the metastasis suppressor miRNA-768-3p holds clinical promise.
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Registered trials
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