IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43293-0.html
   My bibliography  Save this article

Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing

Author

Listed:
  • Lien D. Nguyen

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Zhiyun Wei

    (Brigham and Women’s Hospital and Harvard Medical School
    Tongji University)

  • M. Catarina Silva

    (Massachusetts General Hospital and Harvard Medical School)

  • Sergio Barberán-Soler

    (RealSeq Biosciences)

  • Jiarui Zhang

    (Boston University School of Medicine)

  • Rosalia Rabinovsky

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Christina R. Muratore

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Jonathan M. S. Stricker

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Colin Hortman

    (RealSeq Biosciences)

  • Tracy L. Young-Pearse

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Stephen J. Haggarty

    (Massachusetts General Hospital and Harvard Medical School)

  • Anna M. Krichevsky

    (Brigham and Women’s Hospital and Harvard Medical School)

Abstract

MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for miRNA modulation using oligonucleotides and gene therapies are challenging, especially for neurological diseases, and none have yet gained clinical approval. We explore a different approach by screening a biodiverse library of small molecule compounds for their ability to modulate hundreds of miRNAs in human induced pluripotent stem cell-derived neurons. We demonstrate the utility of the screen by identifying cardiac glycosides as potent inducers of miR-132, a key neuroprotective miRNA downregulated in Alzheimer’s disease and other tauopathies. Coordinately, cardiac glycosides downregulate known miR-132 targets, including Tau, and protect rodent and human neurons against various toxic insults. More generally, our dataset of 1370 drug-like compounds and their effects on the miRNome provides a valuable resource for further miRNA-based drug discovery.

Suggested Citation

  • Lien D. Nguyen & Zhiyun Wei & M. Catarina Silva & Sergio Barberán-Soler & Jiarui Zhang & Rosalia Rabinovsky & Christina R. Muratore & Jonathan M. S. Stricker & Colin Hortman & Tracy L. Young-Pearse & , 2023. "Small molecule regulators of microRNAs identified by high-throughput screen coupled with high-throughput sequencing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43293-0
    DOI: 10.1038/s41467-023-43293-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43293-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43293-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Xiaolan Liu & Xufeng Cen & Ronghai Wu & Ziyan Chen & Yanqi Xie & Fengqi Wang & Bing Shan & Linghui Zeng & Jichun Zhou & Bojian Xie & Yangjun Cai & Jinyan Huang & Yingjiqiong Liang & Youqian Wu & Chao , 2023. "ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Benjamin Readhead & Brigham J. Hartley & Brian J. Eastwood & David A. Collier & David Evans & Richard Farias & Ching He & Gabriel Hoffman & Pamela Sklar & Joel T. Dudley & Eric E. Schadt & Radoslav Sa, 2018. "Author Correction: Expression-based drug screening of neural progenitor cells from individuals with schizophrenia," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    3. Benjamin Readhead & Brigham J. Hartley & Brian J. Eastwood & David A. Collier & David Evans & Richard Farias & Ching He & Gabriel Hoffman & Pamela Sklar & Joel T. Dudley & Eric E. Schadt & Radoslav Sa, 2018. "Expression-based drug screening of neural progenitor cells from individuals with schizophrenia," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    4. M. Catarina Silva & Ghata A. Nandi & Sharon Tentarelli & Ian K. Gurrell & Tanguy Jamier & Diane Lucente & Bradford C. Dickerson & Dean G. Brown & Nicholas J. Brandon & Stephen J. Haggarty, 2020. "Prolonged tau clearance and stress vulnerability rescue by pharmacological activation of autophagy in tauopathy neurons," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      More about this item

      Statistics

      Access and download statistics

      Corrections

      All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43293-0. See general information about how to correct material in RePEc.

      If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

      If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

      For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

      Please note that corrections may take a couple of weeks to filter through the various RePEc services.

      IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.