ArticleNucleic acids research2015
Identification of the endosomal sorting complex required for transport-I (ESCRT-I) as an important modulator of anti-miR uptake by cancer cells.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 56 citations in OpenAlex.
- ESCRT-I complex enhances therapeutic efficacy of ASO drugs by regulating endosomal escape and glucose homeostasis.Molecular therapy. Nucleic acids · 2026Article
- Degron models: a toolbox for rapid in vivo depletion of essential proteins regulating mRNA metabolism.Communications biology · 2026Article
- Non-Coding RNAs in Breast Cancer Radioresistance: Mechanisms, Functional Roles and Translational Potentials.Cell proliferation · 2026Review
- An unbiased whole-genome open reading frame overexpression screen identifies B3GALT2, a novel inducer of cellular ASO activity.Molecular therapy. Nucleic acids · 2025Article
- A genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma.Molecular therapy. Nucleic acids · 2025Article
- High NUP210 mRNA expression and its role in prognosis of acute myeloid leukemia.Clinical and experimental medicine · 2025Article
- A CRISPR/Cas9 screen reveals proteins at the endosome-Golgi interface that modulate cellular anti-sense oligonucleotide activity.Nature communications · 2025Article
- Combining tissue biomarkers with mpMRI to diagnose clinically significant prostate cancer. Analysis of 21 biomarkers in the PICTURE study.Prostate cancer and prostatic diseases · 2025Article
- Endosomal Escape and Nuclear Localization: Critical Barriers for Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2024Review
- Between hope and reality: treatment of genetic diseases through nucleic acid-based drugs.Communications biology · 2024Review
- Cuproptosis-Related Genes MTF1 and LIPT1 as Novel Prognostic Biomarker in Acute Myeloid Leukemia.Biochemical genetics · 2024Article
- MicroRNA-640 Inhibition Enhances the Chemosensitivity of Human Glioblastoma Cells to Temozolomide by Targeting Bcl2 Modifying Factor.Biochemical genetics · 2023Article
- mRNA transcriptome profiling of human hepatocellular carcinoma cells HepG2 treated withWorld journal of hepatology · 2023Article
- Simultaneous inhibition of endocytic recycling and lysosomal fusion sensitizes cells and tissues to oligonucleotide therapeutics.Nucleic acids research · 2023Article
- Review
- CNS Delivery of Nucleic Acid Therapeutics: Beyond the Blood-Brain Barrier and Towards Specific Cellular Targeting.Pharmaceutical research · 2023Review
- Review
- Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias.Journal of clinical medicine · 2022Review
- VPS28 regulates brain vasculature by controlling neuronal VEGF trafficking through extracellular vesicle secretion.iScience · 2022Article
- ncRNAs in Therapeutics: Challenges and Limitations in Nucleic Acid-Based Drug Delivery.International journal of molecular sciences · 2021Review
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Authors and funding
25 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanisms of unassisted delivery of RNA therapeutics, including inhibitors of microRNAs, remain poorly understood. We observed that the hepatocellular carcinoma cell line SKHEP1 retains productive free uptake of a miR-21 inhibitor (anti-miR-21). Uptake of anti-miR-21, but not a mismatch (MM) control, induces expression of known miR-21 targets (DDAH1, ANKRD46) and leads to dose-dependent inhibition of cell growth. To elucidate mechanisms of SKHEP1 sensitivity to anti-miR-21, we conducted an unbiased shRNA screen that revealed tumor susceptibility gene 101 (TSG101), a component of the endosomal sorting complex required for transport (ESCRT-I), as an important determinant of anti-proliferative effects of anti-miR-21. RNA interference-mediated knockdown of TSG101 and another ESCRT-I protein, VPS28, improved uptake of anti-miR-21 in parental SKHEP1 cells and restored productive uptake to SKHEP1 clones with acquired resistance to anti-miR-21. Depletion of ESCRT-I in several additional cancer cell lines with inherently poor uptake resulted in improved activity of anti-miR-21. Finally, knockdown of TSG101 increased uptake of anti-miR-21 by cancer cells in vivo following systemic delivery. Collectively, these data support an important role for the ESCRT-I complex in the regulation of productive free uptake of anti-miRs and reveal potential avenues for improving oligonucleotide free uptake by cancer cells.
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