ArticleMolecular therapy. Nucleic acids2020
Identification of ncRNA-Mediated Functions of Nucleus-Localized miR-320 in Cardiomyocytes.
Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026Review
- The paradox of nuclear miRNAs: Mechanisms, therapeutic potential, and future directions.Non-coding RNA research · 2026Review
- The roles of subcellular Argonaute 2 in cardiovascular diseases.Journal of translational internal medicine · 2025Article
- Predictive value of miR-637 for the occurrence of myocardial hypertrophy in patients with hypertension.Journal of cardiothoracic surgery · 2025Article
- RNAa: Mechanisms, therapeutic potential, and clinical progress.Molecular therapy. Nucleic acids · 2025Review
- PMiSLocMF: predicting miRNA subcellular localizations by incorporating multi-source features of miRNAs.Briefings in bioinformatics · 2024Article
- Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2024Article
- Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy.Science China. Life sciences · 2024Article
- Nuclear miRNAs: Gene Regulation Activities.International journal of molecular sciences · 2024Review
- Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.International journal of molecular sciences · 2024Review
- The Mechanisms of miRNAs on Target Regulation and their Recent Advances in Atherosclerosis.Current medicinal chemistry · 2024Review
- Nuclear lncRNA NORSF reduces E2 release in granulosa cells by sponging the endogenous small activating RNA miR-339.BMC biology · 2023Article
- The Roles of microRNAs in the Cardiovascular System.International journal of molecular sciences · 2023Review
- Noncoding RNAs in Vascular Cell Biology and Restenosis.Biology · 2022Review
- Non-canonical features of microRNAs: paradigms emerging from cardiovascular disease.Nature reviews. Cardiology · 2022Review
- A Mutation in Endogenous saRNA miR-23a Influences Granulosa Cells Response to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Article
- MicroRNAs as therapeutic targets in cardiovascular disease.The Journal of clinical investigation · 2022Review
- miR-2337 induces TGF-β1 production in granulosa cells by acting as an endogenous small activating RNA.Cell death discovery · 2021Article
- Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In recent years, systematic analyses of the subcellular distribution of microRNAs (miRNAs) suggest that the majority of miRNAs are present in both nuclear and cytoplasmic compartments. However, the full extent of nuclear miRNA function in cardiomyocytes is currently unknown. Here, subcellular fractionation, followed by the miRNA microarray, revealed that most miRNAs were detectable in both nuclear and cytoplasmic fractions of cardiomyocytes. We employed miR-320 as an example to explore the function of nucleus-localized miRNAs, finding that CRISPR-Cas9-mediated Ago2 knockdown abolished miR-320-induced transcriptional remodeling. Furthermore, nuclear Ago2 re-expression restored the effects of miR-320 in the nucleus. Moreover, liquid chromatography-mass spectrometry (LC-MS) analysis revealed the association of nuclear Ago2 with transcription factors YLP motif-containing protein 1 (Ylpm1) and single-stranded DNA binding protein 1 (Ssbp1). Intersection of the data of transcriptome-sequencing (seq) with Ago2-chromatin immunoprecipitation (ChIP)-seq revealed that the binding of Ago2 with the target promoter DNA may require promoter RNAs. Specifically, Cep57 was upregulated, whereas Fscn2 was downregulated by miR-320, and a similar effect was also observed by knockdown of their promoter RNA, respectively. Chromatin isolation by RNA purification (ChIRP) analysis showed decreased binding of the Cep57 and Fscn2 promoter RNA on their promoter DNA by miR-320 overexpression.Our work provided a preliminary idea that promoter RNA transcripts act as "pioneers" to disrupt chromatin that permits Ago2/miR-320 complexes to target Cep57 or Fscn2 promoter DNA for transcriptional regulation. miRNAs are naturally located in both cytoplasm and nucleus; however, their pathophysiological functions are largely unknown. Our work provided a theoretical basis for developing nuclear miRNA-based therapeutics against various diseases in the future.
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