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MicroRNA 28 (miR-28) is a small, non-coding RNA molecule processed from the MIR28 gene in humans, located within intron 6 of the LPP gene on chromosome 3q28. As a microRNA, miR-28 functions via post-transcriptional gene silencing, binding imperfectly to complementary sites in target messenger RNA (mRNA) 3’ untranslated regions, primarily resulting in translational inhibition or mRNA destabilization. Two mature forms are produced from its precursor: miR-28-5p and miR-28-3p. Functionally, miR-28 plays a critical role in regulating cell proliferation, cell cycle, and apoptosis. It has been identified as a context-dependent regulator: acting as a tumor suppressor in B-cell lymphoma and colorectal cancer by inhibiting cell proliferation and clonogenic properties (through repression of targets such as MAD2L1 and BAG1), and as an oncogene in other cancers such as gastric and ovarian cancer (by targeting PTEN and other genes). Its expression is frequently altered in malignancies—in some, it is down-regulated (e.g., Burkitt lymphoma, colorectal cancer), while in others it is overexpressed (e.g., esophageal, renal cancer). miR-28 is also involved in immune regulation, including repression of HIV-1 gene expression in resting CD4+ T cells. Due to its regulatory roles and frequent involvement in cancer and viral infection, miR-28 represents a potential biomarker for disease as well as a target for miRNA-based therapeutics; however, as with many microRNAs, there are significant challenges related to pleiotropic effects and target specificity. No approved drugs directly target miR-28, though research into miRNA mimics or inhibitors to modulate its function in oncology and virology is ongoing.
drugs or mimics that upregulate miR-28 could restore its tumor-suppressive function by repressing target mRNAs that promote cell proliferation (e.g., MYC pathway), while inhibitors of miR-28 could relieve suppression of gene targets in contexts where miR-28 acts as an oncogene
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