MicroRNA 3189 (miR-3189)

MicroRNA 3189 (miR-3189) is a primate-specific, non-coding RNA molecule embedded within the intron of the growth differentiation factor 15 (GDF15) gene and regulated by p53. It mainly produces the 3p miRNA (miR-3189-3p), which acts as a potent tumor suppressor by inhibiting cell proliferation, migration, and invasion, and inducing apoptosis in cancer cells. miR-3189 downregulates a broad array of genes involved in cell cycle control and cell survival, in particular targeting mRNAs such as 4E-BP1 (EIF4EBP1), SF3B2, and p63RhoGEF, indirectly reducing oncogene (such as c-MYC) expression. The microRNA exerts these effects through both p53-dependent and p53-independent mechanisms, and its expression is epigenetically regulated, such as by H3K27me3 modification in glioblastoma. miR-3189 is markedly downregulated in several cancers, including glioblastoma and gastric cancer, and experimental restoration of its expression suppresses tumor cell growth, migration, and enhances apoptosis. As a target, it is being explored for therapeutic RNA-based approaches and as a biomarker in oncology. Key references: - miR-3189-3p targets translational regulatory proteins and indirectly inhibits c-MYC; suppresses cell proliferation and promotes apoptosis and distinct metabolic states in breast cancer and glioblastoma. - Downregulation of miR-3189-3p is observed in glioblastoma and gastric cancer, and restoration inhibits key cancer cell phenotypes and tumor aggressiveness. Epigenetic control through PRC2/H3K27me3 silences miR-3189-3p, leading to activation of malignancy-promoting genes such as COL6A2. No approved drugs directly target miR-3189 as of now; strategies involve miRNA mimics and gene therapy approaches. Safety and efficacy profiles are under preclinical investigation.

Other names

hsa-miR-3189MIR3189miR-3189-3phsa-mir-3189

No direct drugs, but as a microRNA, mechanism is through RNA-induced silencing complex (RISC)-mediated translational inhibition or degradation of target mRNAs; therapeutic strategies may involve miR-3189 mimics