ArticleACS chemical biology2015
Small Molecule Inhibition of miR-544 Biogenesis Disrupts Adaptive Responses to Hypoxia by Modulating ATM-mTOR Signaling.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- MicroRNA Guided In Silico Drug Repositioning for Malaria.Acta parasitologica · 2024Article
- Graph neural networks for the identification of novel inhibitors of a small RNA.SLAS discovery : advancing life sciences R & D · 2023Article
- Contemporary Progress and Opportunities in RNA-Targeted Drug Discovery.ACS medicinal chemistry letters · 2023Review
- Hypoxia-driven ncRNAs in breast cancer.Frontiers in oncology · 2023Review
- Low-Molecular Weight Small Molecules Can Potently Bind RNA and Affect Oncogenic Pathways in Cells.Journal of the American Chemical Society · 2022Article
- Expansion of the RNAStructuromeDB to include secondary structural data spanning the human protein-coding transcriptome.Scientific reports · 2022Article
- Review
- Long non-coding RNAs as possible therapeutic targets in protozoa, and in Schistosoma and other helminths.Parasitology research · 2022Review
- MicroRNAs as a clue to overcome breast cancer treatment resistance.Cancer metastasis reviews · 2022Review
- Preclinical Imaging Evaluation of miRNAs' Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review.Cancers · 2021Review
- Systematically Studying the Effect of Small Molecules Interacting with RNA in Cellular and Preclinical Models.ACS chemical biology · 2021Review
- Therapeutic Targeting of MicroRNAs in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Understanding the characteristics of nonspecific binding of drug-like compounds to canonical stem-loop RNAs and their implications for functional cellular assays.RNA (New York, N.Y.) · 2021Article
- Targeting RNA structures in diseases with small molecules.Essays in biochemistry · 2020Review
- How We Think about Targeting RNA with Small Molecules.Journal of medicinal chemistry · 2020Article
- Target-Directed Approaches for Screening Small Molecules against RNA Targets.SLAS discovery : advancing life sciences R & D · 2020Review
- Gini Coefficients as a Single Value Metric to Define Chemical Probe Selectivity.ACS chemical biology · 2020Article
- Identification of long noncoding RNAs involved in adaptability to chronic hypoxic by whole transcriptome sequencing.3 Biotech · 2020Article
- miRNA inhibition by proximity-enabled Dicer inactivation.Methods (San Diego, Calif.) · 2019Article
- miR-92b-3p-TSC1 axis is critical for mTOR signaling-mediated vascular smooth muscle cell proliferation induced by hypoxia.Cell death and differentiation · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia induces a complex circuit of gene expression that drives tumor progression and increases drug resistance. Defining these changes allows for an understanding of how hypoxia alters tumor biology and informs design of lead therapeutics. We probed the role of microRNA-544 (miR-544), which silences mammalian target of rapamycin (mTOR), in a hypoxic breast cancer model by using a small molecule (1) that selectively impedes the microRNA's biogenesis. Application of 1 to hypoxic tumor cells selectively inhibited production of the mature microRNA, sensitized cells to 5-fluorouracil, and derepressed mRNAs affected by miR-544 in cellulo and in vivo, including boosting mTOR expression. Thus, small molecule inhibition of miR-544 reverses a tumor cell's physiological response to hypoxia. Importantly, 1 sensitized tumor cells to hypoxia-associated apoptosis at a 25-fold lower concentration than a 2'-O-methyl RNA antagomir and was as selective. Further, the apoptotic effect of 1 was suppressed by treatment of cell with rapamycin, a well-known inhibitor of the mTOR signaling pathway, illustrating the selectivity of the compound. Thus, RNA-directed chemical probes, which could also serve as lead therapeutics, enable interrogation of complex cellular networks in cells and animals.
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