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Cyclin-dependent kinase inhibitor 2B antisense RNA 1, widely known as ANRIL, is a long non-coding RNA (lncRNA) located at the CDKN2A/B locus on chromosome 9p21.3. It plays a pivotal role in cellular homeostasis by epigenetically silencing the INK4/ARF tumor suppressor cluster through the recruitment of Polycomb Repressive Complexes (PRC1 and PRC2), which leads to increased cell proliferation and decreased senescence. ANRIL also functions as a molecular sponge for various microRNAs, thereby indirectly regulating multiple oncogenic and inflammatory signaling pathways. Its overexpression is a hallmark of many cancers, including breast, lung, and liver cancer, where it correlates with poor prognosis and metastasis. Additionally, genetic variants and dysregulation of ANRIL are strongly associated with increased risk for coronary artery disease, atherosclerosis, and type 2 diabetes. As a therapeutic target, ANRIL is being explored through RNA-interference and antisense oligonucleotide strategies to restore the expression of tumor suppressors and enhance the efficacy of conventional chemotherapeutic agents.
Modulation of gene expression through recruitment of Polycomb Repressive Complexes (PRC1/PRC2) for epigenetic silencing and acting as a competitive endogenous RNA (ceRNA) to sponge microRNAs.
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