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

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. Coo

SUBMITTER: Nguyen LD 

PROVIDER: S-EPMC10663445 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature