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Pre-microRNA-21 (pre-miR-21) is the precursor hairpin structure of microRNA-21, a potent "oncomiR" that is frequently overexpressed in a wide variety of human cancers and fibrotic diseases (PubMed: 22330140). It is generated in the nucleus from the primary transcript (pri-miR-21) by the Drosha-DGCR8 complex and subsequently exported to the cytoplasm, where it is cleaved by the Dicer enzyme to produce the mature miR-21 duplex (PubMed: 29030422). The mature form of miR-21 acts as a post-transcriptional regulator by binding to the 3' untranslated regions of target mRNAs, such as PTEN and PDCD4, leading to their degradation or translational repression (PubMed: 21150131). This regulation promotes oncogenic processes including cell survival, proliferation, and epithelial-mesenchymal transition, while also driving pathological fibrosis in organs like the kidney and heart (PubMed: 24901532). Due to its central role in disease progression, pre-miR-21 has become a significant therapeutic target for antisense oligonucleotides and small molecule inhibitors designed to block its maturation or activity (PubMed: 30103528). Clinical candidates like Lademirsen (RG-012) have been developed to target miR-21 for the treatment of Alport syndrome and other fibrotic conditions (ClinicalTrials.gov: NCT02855268).
Inhibition of microRNA maturation by blocking Dicer-mediated cleavage of the precursor hairpin or antisense-mediated sequestration of the mature/precursor sequence.
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