{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FIRRE is a highly conserved long noncoding RNA that plays multifaceted roles in nuclear organization, regulation of epigenetic states, and modulation of gene expression in various cellular contexts. Notably, FIRRE has been shown to anchor the inactive X chromosome to the perinucleolar region and preserve its key epigenetic mark (H3K27me3), thereby contributing to the maintenance of its unique higher‐order architecture by facilitating chromatin superloop formation and inter‐chromosomal interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its architectural role, FIRRE is responsive to inflammatory stimuli. Its transcription is induced via NF-κB signaling in cells such as macrophages and intestinal epithelial cells, where FIRRE, by interacting with heterogeneous nuclear ribonucleoprotein U (hnRNPU), enhances the expression of inflammatory genes through posttranscriptional stabilization of mRNAs via AU-rich element targeting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n FIRRE activity has also been implicated in tumorigenesis. In diffuse large B-cell lymphoma and colorectal cancer, aberrant upregulation of FIRRE promotes oncogenic behaviors. In these settings, FIRRE facilitates tumor cell proliferation by activating pathways such as Wnt/β-catenin—via promoting the nuclear translocation of β-catenin—or by stabilizing transcripts like BECN1 through its interaction with RNA-binding proteins such as PTBP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, differential FIRRE expression may have prognostic significance, as higher levels have been associated with improved overall survival in certain colorectal cancer patient cohorts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings support a context-dependent role for FIRRE in regulating nuclear architecture, inflammatory responses, and oncogenic processes, underscoring its importance as a multifunctional regulatory RNA in both normal physiology and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fan Yang, Xinxian Deng, Wenxiu Ma, et al. 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