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The 3' untranslated region (UTR) of the Acyl-CoA synthetase long chain family member 4 (ACSL4) mRNA is a critical regulatory element that controls the expression of the ACSL4 enzyme (PMID: 32864145). ACSL4 plays a pivotal role in ferroptosis, a form of regulated cell death, by facilitating the incorporation of long-chain polyunsaturated fatty acids into phospholipids (Nature Chemical Biology, 2017). The 3' UTR contains binding sites for various microRNAs, such as miR-211-5p, miR-424-5p, and miR-199a-5p, which modulate mRNA stability and translation efficiency (PMID: 33061145, PMID: 31484324). In many cancers, dysregulation of these regulatory interactions leads to ACSL4 overexpression, which can either promote or suppress tumor growth depending on the context of ferroptosis sensitivity. Therapeutic strategies targeting this region, such as antisense oligonucleotides or miRNA mimics, aim to precisely tune ACSL4 levels to treat malignancies or protect tissues from oxidative damage. Consequently, the ACSL4 mRNA 3' UTR represents a significant target for precision medicine in oncology and metabolic diseases.
Binding to the 3' untranslated region to induce mRNA degradation or inhibit translation, thereby reducing ACSL4 protein expression and suppressing ferroptosis.
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