MicroRNA 21 (miR-21) (miR-21)

MicroRNA 21 (miR-21) is a highly conserved non-coding RNA that serves as a critical regulator of gene expression and is one of the most frequently cited "oncomirs" in human cancer (PubMed: 21475224). It is synthesized as a primary transcript (pri-miR-21) in the nucleus, which is then processed into a precursor hairpin (pre-miR-21) and finally into the mature functional miRNA that targets tumor suppressor genes like PTEN and PDCD4 (PubMed: 18230677). Beyond its oncogenic role in promoting cell survival and proliferation, miR-21 is a central mediator of pathological fibrosis in the heart, lungs, and kidneys by enhancing TGF-beta signaling (PubMed: 21123950). Because of its involvement in multiple disease states, miR-21 precursors have become significant therapeutic targets. Current drug development efforts focus on antisense oligonucleotides, such as Lademirsen, which prevent miRNA maturation or activity, and small molecules designed to bind the pre-miR-21 structure to inhibit Dicer-mediated processing (PubMed: 29155424, ClinicalTrials.gov: NCT02855268). These therapeutic strategies aim to restore the expression of protective genes and are currently being evaluated in clinical trials for conditions such as Alport syndrome and various malignancies.

Other names

Primary microRNA 21Precursor microRNA 21MIR21hsa-mir-21Oncomir-21pri-miR-21pre-miR-21

Therapeutic agents targeting pri-miR-21 or pre-miR-21 primarily function through two mechanisms: antisense oligonucleotides (ASOs) bind to the miRNA sequence to induce RNase H-mediated degradation or steric blockade of the processing machinery, while small molecules bind to the specific secondary structure (stem-loop) of the precursor to inhibit cleavage by the Drosha or Dicer complexes (PubMed: 29155424, PubMed: 32814728).