{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Studies on the long non‐coding RNA C5orf66‐AS1 reveal context‐dependent roles in cancer. In cervical cancer, C5orf66‐AS1 is markedly upregulated, where it functions as a competing endogenous RNA by “sponging” miR‑637 to upregulate RING1, thereby promoting cell proliferation and suppressing apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, in hepatocellular carcinoma–derived cancer stem cells, mesenchymal stem cell‐derived exosomes induce C5orf66‐AS1 expression; in this setting, C5orf66‐AS1 sequesters miR‑127‑3p to enhance DUSP1 levels, which in turn reduces malignant cell behaviors, indicating a tumor‐suppressive role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in pituitary null cell adenomas, decreased expression of C5orf66‐AS1 correlates with increased invasiveness, and its overexpression in vitro inhibits cell viability and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Epigenetic analyses in head and neck squamous cell carcinoma have revealed hypermethylation of the C5orf66‐AS1 locus, with resultant downregulation associated with poorer prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In osteosarcoma, however, C5orf66‐AS1 is upregulated and acts in an oncogenic manner by sponging miR‑149‑5p; knockdown of C5orf66‐AS1 reduces proliferation, migration, and invasion while promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In gastric cancer and gastric cardia adenocarcinoma, lower levels of C5orf66‐AS1 due to aberrant hypermethylation have been reported; functionally, restoration of C5orf66‐AS1 suppresses cell proliferation, migration, and invasion and enhances apoptosis, thereby linking its loss to advanced disease and poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In oral squamous cell carcinoma, diminished expression of C5orf66‐AS1 contributes to tumor progression via upregulation of CYC1, whereas its overexpression inhibits proliferation, migration, and invasion while promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In triple‐negative breast cancer, elevated levels of C5orf66‐AS1 act oncogenically by sponging miR‑149‑5p and modulating the Wnt/β‑catenin pathway through upregulation of CTNNB1, thereby enhancing malignant cell behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings suggest that C5orf66‐AS1 can either function as an oncogene or a tumor suppressor depending on the cancer type. Its actions are largely mediated through interactions with specific microRNAs that alter the expression of key downstream effectors involved in cell proliferation, apoptosis, migration, and invasion. Moreover, epigenetic modifications—including aberrant hypermethylation—appear to be critical in modulating its expression and, consequently, its prognostic significance across different malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiaohui Rui, Yun Xu, Xiping Jiang, et al. 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