{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00657, also known as NORAD, is an evolutionarily conserved and abundantly expressed cytoplasmic long non‐coding RNA that is rapidly induced by DNA damage and plays a key role in safeguarding genomic stability by sequestering Pumilio RNA‐binding proteins, thereby ensuring proper mitotic division and chromosome segregation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Beyond its role in genome maintenance, LINC00657 functions as a competing endogenous RNA (ceRNA) in a context‐dependent manner. In several cancer types—such as breast cancer, non‐small cell lung cancer, osteosarcoma, colorectal cancer, and prostate cancer—it is frequently upregulated and promotes tumor progression by sponging specific microRNAs (including miR‑26b‑5p, miR‑106a‑5p, miR‑199a‑3p, and miR‑541‑3p) to indirectly elevate the expression of oncogenic factors such as COMMD8, promote cell proliferation, enhance migration, induce epithelial‐to‐mesenchymal transition, and even contribute to therapy resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": " Conversely, studies in hepatocellular and cervical cancers have reported downregulation of LINC00657, where its overexpression suppresses malignant phenotypes by modulating microRNA networks—for instance, enhancing PTEN expression or promoting the RUNX3/DR5 axis—and thereby inhibiting proliferation, migration, invasion, and tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, LINC00657 has been implicated in non-cancerous conditions: for example, it is upregulated following nerve injury and contributes to the development of neuropathic pain via a miR‑136/ZEB1-mediated neuroinflammatory mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings demonstrate that LINC00657/NORAD is a multifunctional regulator whose ability to control genomic stability and modulate key signaling networks through microRNA interactions renders it a potential diagnostic biomarker and therapeutic target in diverse pathological contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sungyul Lee, Florian Kopp, Tsung-Cheng Chang, et al. 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