{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLong non‐coding RNA PART1 is emerging as a multifaceted regulator in human diseases, particularly in cancer, where its function appears to be highly context‐dependent. In several malignancies, PART1 acts as an oncogene. For instance, in colorectal cancer, elevated PART1 expression promotes tumor progression by serving as a competing endogenous RNA – sponging miR‑143 to up‐regulate DNMT3A ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "], and by sequestering miR‑150‑5p/miR‑520h as well as miR‑150‑5p to regulate targets like CTNNB1 and LRG1, thereby activating the Wnt/β‑catenin pathway ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]. Similarly, in non‑small cell lung cancer, PART1 is robustly induced and promotes cell proliferation, migration, invasion, and activation of the JAK‑STAT signaling cascade through sponging miR‑635 ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. Additional oncogenic roles have been reported in bladder cancer ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "], glioma via a PART1–hsa‑miR‑429–SHCBP1 regulatory network ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "], breast cancer where increased PART1 expression supports proliferation and chemoresistance to cisplatin ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "], pancreatic cancer ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "], and ovarian cancer in which PART1 facilitates malignant progression by acting on downstream effectors such as RACGAP1 and RRM2 or by modulating mitophagy ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]. Furthermore, exosome‐mediated delivery of PART1 has been implicated in the promotion of oral squamous cell carcinoma progression ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, PART1 exhibits tumor‑suppressive functions in other cancer types. For example, in gastric cancer, PART1 is significantly downregulated and its low expression is associated with postoperative metastasis and poor survival. Mechanistically, PART1 interacts with the androgen receptor (AR) to induce PLZF expression, which in turn recruits epigenetic modifiers that silence PDGFB expression and inhibit the downstream PDGFRβ/PI3K/Akt pathway ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "]. A similar tumor‑suppressive role is evidenced in esophageal squamous cell carcinoma, where PART1 overexpression suppresses cell proliferation and invasion through sponging miR‑18a‑5p and up‑regulating SOX6 ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, PART1 is involved in various non‑neoplastic diseases. In osteoarthritis, research has revealed that PART1 is downregulated in cartilage, and its overexpression can attenuate interleukin‑1β–induced chondrocyte apoptosis by sponging miR‑590‑3p to modulate the TGFBR2/Smad3 signaling cascade ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "]. Although its role in osteoarthritis remains partially undefined ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "], PART1 has also been implicated in myocardial ischemia‑reperfusion injury via regulation of BIRC5 through a miR‑503‑5p–dependent mechanism. Its dysregulation in endothelial cells contributes to blood–brain barrier dysfunction in Alzheimer’s disease models by destabilizing PPP2R3A through STAU1‑mediated mRNA degradation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "]. The role of PART1 in osteogenic differentiation of human bone marrow–derived mesenchymal stem cells is also under active investigation ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have underscored the multifaceted contributions of PART1 in cancer beyond its pro‑ or anti‑tumorigenic actions. In epithelial ovarian carcinoma, PART1 is implicated in disease development ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "], while in breast and ovarian cancers distinct mechanisms link PART1 expression with chemotherapeutic responses – including modulation of mitophagy through regulation of PHB2, which can influence platinum and PARP inhibitor sensitivity ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. A comprehensive review also highlights the dual roles of PART1 – functioning as an oncogene in some contexts and as a tumor suppressor in others – by regulating cell proliferation, apoptosis, invasion, and metastasis via diverse molecular mechanisms ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "]. Genetic association studies have further explored PART1 polymorphisms in conditions such as dental caries ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "].\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yongbo Hu, Zhen Ma, Yiming He, et al. 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