{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LINC00339 is a multifunctional long noncoding RNA that plays diverse regulatory roles in both cancer‐related and nonmalignant diseases. In musculoskeletal disorders, for example, genetic variants within regulatory regions at 1p36.12 form long‐range chromatin loops that increase LINC00339 expression, thereby modulating downstream targets such as CDC42 and contributing to osteoporosis pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In several cancers, LINC00339 functions as an oncogenic competing endogenous RNA: it sponges tumor suppressor microRNAs—including miR‑377‑3p in triple‐negative breast cancer and gastric cancer, miR‑145 in non‐small cell lung and laryngeal carcinomas, miR‑497‑5p in pancreatic cancer, miR‑152 in hepatocellular carcinoma, and miR‑539‑5p in glioma—leading to the derepression of oncogenic effectors such as HOXC6, FOXM1, IGF1R, DCP1A, ROCK1, and TWIST1 that drive cell proliferation, migration, invasion, and resistance to apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "7"}]}, {"type": "t", "text": " Moreover, LINC00339 has been implicated in glioma, where its suppression by therapeutic agents correlates with reduced tumor growth, and in endometrial disorders, where altered expression within lesion foci impacts immune‐related gene networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Additional studies have highlighted its role in other pathological settings, such as in gastric cancer via regulation of DCP1A (which reinforces its pro‑tumorigenic function), in renal epithelial cell pyroptosis through modulation of the NLRP3 inflammasome via miR‑22‑3p, and in doxorubicin‑induced cardiotoxicity by targeting miR‑484."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "13"}]}, {"type": "t", "text": " Finally, the inclusion of LINC00339 in prognostic signatures further supports its clinical potential as a diagnostic and therapeutic target across multiple human cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "and underscores its contribution to disease mechanisms such as abnormal bone turnover in osteoporosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiao-Feng Chen, Dong-Li Zhu, Man Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An Osteoporosis Risk SNP at 1p36.12 Acts as an Allele-Specific Enhancer to Modulate LINC00339 Expression via Long-Range Loop Formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2018.03.001"}], "href": "https://doi.org/10.1016/j.ajhg.2018.03.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29706346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29706346"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joseph E Powell, Jenny N Fung, Konstantin Shakhbazov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endometriosis risk alleles at 1p36.12 act through inverse regulation of CDC42 and LINC00339."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddw320"}], "href": "https://doi.org/10.1093/hmg/ddw320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28171565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28171565"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaolong Wang, Tong Chen, Yan Zhang, et al. 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