ArticleCell chemical biology2022
A structure-specific small molecule inhibits a miRNA-200 family member precursor and reverses a type 2 diabetes phenotype.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- miRNAs as cell-intrinsic epigenetic regulators in muscle in type 2 diabetes.Signal transduction and targeted therapy · 2026Article
- SHAPE-Based Chemical Probes for Studying preQACS chemical biology · 2025Article
- Global Perspectives on Coronary Artery Disease: The Emerging Role of miRNAs.Current atherosclerosis reports · 2025Review
- A review on gut microbiota and miRNA crosstalk: implications for Alzheimer's disease.GeroScience · 2025Review
- Harnessing Computational Approaches for RNA-Targeted Drug Discovery.RNA nanomed · 2024Article
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- Small molecules targeting microRNAs: new opportunities and challenges in precision cancer therapy.Trends in cancer · 2024Review
- Gut-Liver-Pancreas Axis Crosstalk in Health and Disease: From the Role of Microbial Metabolites to Innovative Microbiota Manipulating Strategies.Biomedicines · 2024Review
- Targeting MicroRNAs with Small Molecules.Non-coding RNA · 2024Review
- Small molecule approaches to targeting RNA.Nature reviews. Chemistry · 2024Review
- Recent progress in miRNA biogenesis and decay.RNA biology · 2024Review
- Article
- Amplifying gene expression with RNA-targeted therapeutics.Nature reviews. Drug discovery · 2023Review
- Contemporary Progress and Opportunities in RNA-Targeted Drug Discovery.ACS medicinal chemistry letters · 2023Review
- Identifying SM-miRNA associations based on layer attention graph convolutional network and matrix decomposition.Frontiers in molecular biosciences · 2022Article
- Screening and analysis of differentially expressed circRNAs and miRNAs in chronic diabetic extremity wounds.Frontiers in surgery · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
MicroRNA families are ubiquitous in the human transcriptome, yet targeting of individual members is challenging because of sequence homology. Many secondary structures of the precursors to these miRNAs (pri- and pre-miRNAs), however, are quite different. Here, we demonstrate both in vitro and in cellulis that design of structure-specific small molecules can inhibit a particular miRNA family member to modulate a disease pathway. The miR-200 family consists of five miRNAs, miR-200a, -200b, -200c, -141, and -429, and is associated with type 2 diabetes (T2D). We designed a small molecule that potently and selectively targets pre-miR-200c's structure and reverses a pro-apoptotic effect in a pancreatic β cell model. In contrast, an oligonucleotide targeting the RNA's sequence inhibited all family members. Global proteomics and RNA sequencing analyses further demonstrate selectivity for miR-200c. Collectively, these studies establish that miR-200c plays an important role in T2D, and small molecules targeting RNA structure can be an important complement to oligonucleotides.
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Registered trials
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.