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miR-129 mimic is a synthetic double-stranded microRNA-129 replacement construct, often chemically modified by substituting uracil with 5‑fluorouracil (5‑FU), being developed as an experimental anticancer RNA therapeutic. 5‑FU–modified miR‑129 mimics (notably the candidate termed Mimic‑1) retain the native miR‑129 seed sequence and target spectrum while gaining increased stability, vehicle‑free cellular uptake, and additional cytotoxicity from intracellular release of 5‑FU metabolites that inhibit thymidylate synthase. These mimics downregulate multiple oncogenic and survival pathways by directly targeting transcripts such as BCL2, HMGB1, and E2F3, leading to G1 cell‑cycle arrest, apoptosis, and inhibition of proliferation in colorectal and non‑small cell lung cancer models, including chemotherapy‑ and tyrosine kinase inhibitor‑resistant cancer stem cell populations in vitro and in vivo.[1][3][4][6]
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