ArticleScientific reports2020
Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Prognostic model construction and drug prediction in colorectal cancer using mitochondrial programmed cell death-related genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- Caspases as master regulators of programmed cell death: apoptosis, pyroptosis and beyond.Experimental & molecular medicine · 2025Review
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
- Review
- Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis.International journal of molecular sciences · 2023Review
- A Novel Defined PANoptosis-Related miRNA Signature for Predicting the Prognosis and Immune Characteristics in Clear Cell Renal Cell Carcinoma: A miRNA Signature for the Prognosis of ccRCC.International journal of molecular sciences · 2023Article
- Identification of a pyroptosis-related long non-coding RNA Signature for prognosis and its related ceRNA regulatory network of ovarian cancer.Journal of Cancer · 2023Article
- Melatonin Modulation of Radiation-Induced Molecular Changes in MCF-7 Human Breast Cancer Cells.Biomedicines · 2022Article
- Acid Sphingomyelinase, a Lysosomal and Secretory Phospholipase C, Is Key for Cellular Phospholipid Catabolism.International journal of molecular sciences · 2021Review
- Connecting Cholesterol Efflux Factors to Lung Cancer Biology and Therapeutics.International journal of molecular sciences · 2021Review
- Contribution of podocyte inflammatory exosome release to glomerular inflammation and sclerosis during hyperhomocysteinemia.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- MicroRNA-494 Regulates Endoplasmic Reticulum Stress in Endothelial Cells.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Activation of acid sphingomyelinase (SMPD1) and the generation of ceramide is a critical regulator of apoptosis in response to cellular stress including radiation. Endothelial SMPD1 has been shown to regulate tumor responses to radiation therapy. We show here that the SMPD1 gene is regulated by a microRNA (miR), miR-15a, in endothelial cells (ECs). Standard low dose radiation (2 Gy) upregulates miR-15a and decreases SMPD1 levels. In contrast, high dose radiation (10 Gy and above) decreases miR-15a and increases SMPD1. Ectopic expression of miR-15a decreases both mRNA and protein levels of SMPD1. Mimicking the effects of high dose radiation with a miR-15a inhibitor decreases cell proliferation and increases active Caspase-3 & 7. Mechanistically, inhibition of miR-15a increases inflammatory cytokines, activates caspase-1 inflammasome and increases Gasdermin D, an effector of pyroptosis. Importantly, both systemic and vascular-targeted delivery of miR-15a inhibitor decreases angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. Taken together, our findings highlight a novel role for miR mediated regulation of SMPD1 during radiation responses and establish proof-of-concept that this pathway can be targeted with a miR inhibitor.
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