{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC‐PINT is a p53‐induced long intergenic noncoding RNA that has emerged as a multifaceted regulator of gene expression and cellular homeostasis. Multiple independent studies have demonstrated that LINC‐PINT predominantly functions as a tumor suppressor in a range of cancers—including glioblastoma, gastric, lung, esophageal, ovarian, laryngeal, melanoma, and colorectal cancers—where its downregulation correlates with enhanced cell proliferation, migration, invasion, and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, LINC‐PINT exerts its tumor‐suppressive effects through diverse pathways. In certain contexts, it modulates epigenetic silencing by directly interacting with the Polycomb repressive complex 2 (PRC2) to target key genes for H3K27 trimethylation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in glioblastoma a circular RNA derived from LINC‐PINT encodes an 87–amino acid peptide that binds to the polymerase associated factor complex (PAF1c) to inhibit transcriptional elongation of oncogenes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Additionally, LINC‐PINT functions as a molecular “sponge” for several microRNAs—including miR‐21, miR‐543, miR‐576‐5p, miR‐208a‐3p, miR‐374a‐5p, miR‐523‐3p, and miR‐155‐5p—thereby regulating downstream effectors such as PDCD4, PTEN, DKK1, and SOCS1 that govern cellular proliferation, apoptosis, migration, invasion, and response to chemotherapeutics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in tumorigenesis, LINC‐PINT is implicated in non‐neoplastic conditions. For instance, its increased expression in neurons appears to offer neuroprotection in Parkinson’s disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", while in the context of diabetes, LINC‐PINT supports pancreatic β–cell function and its overexpression mitigates complications such as cardiomyopathy and retinopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Moreover, genetic polymorphisms in the LINC‐PINT gene have been associated with altered susceptibility to a range of conditions—including rheumatoid arthritis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", hepatitis C-induced lipogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", high–altitude pulmonary edema"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", steroid–induced osteonecrosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", and autoimmune diseases such as pemphigus foliaceus"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", as well as modulating vascular pathology in Alzheimer’s disease‐related cerebral amyloid angiopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, LINC‐PINT influences the therapeutic response of tumors by enhancing radiosensitivity in nasopharyngeal carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "and by sensitizing triple-negative breast cancer cells to chemotherapeutic agents through interactions that destabilize RNA-binding proteins such as NONO."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " A global review of LINC‐PINT’s functions further underscores its clinical potential as a diagnostic biomarker and therapeutic target in diverse pathological settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LINC‐PINT exerts critical roles in modulating tumor progression and non–cancer disease processes through a spectrum of mechanisms—including epigenetic modulation, microRNA sponging, and even the production of regulatory peptides—thus representing a promising target for future therapeutic interventions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maolei Zhang, Kun Zhao, Xiaoping Xu, et al. 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