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NOP16 small interfering RNA (siRNA) and NOP16 short hairpin RNA (shRNA) are experimental RNA interference (RNAi) therapies designed to inhibit the expression of Nucleolar protein 16 (NOP16). NOP16 has been characterized as an endogenous mammalian protein that functions as a histone H3K27 mimic, competing with histone H3 for binding to the Polycomb Repressive Complex 2 (PRC2) component EED and the H3K27 demethylase JMJD3. By sequestering EED from the nucleoplasm to the nucleolus, NOP16 negatively regulates H3K27 trimethylation, thereby derepressing genes involved in cell cycle progression, growth, and apoptosis. In breast cancer, particularly triple-negative breast cancer (TNBC), NOP16 is frequently overexpressed and correlates with poor prognosis. The use of siRNA and shRNA to deplete NOP16 levels has demonstrated significant anti-tumor activity in preclinical models, including induction of cell cycle arrest, inhibition of cell proliferation, and reduction of tumor growth in vivo.
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