{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA IGF2‐AS, transcribed from the antisense strand of the IGF2 locus, plays multifaceted and context‐dependent roles in cellular regulation. In gastrointestinal malignancies, such as gastric adenocarcinoma and colorectal cancer, IGF2‐AS is upregulated and functions as an oncogenic competitive endogenous RNA that sponges specific microRNAs (e.g., miR‑503 and miR‑150) to modulate downstream effectors and promote cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast, in prostate cancer and hepatocellular carcinoma, IGF2‐AS is downregulated and its overexpression suppresses tumor cell growth and invasive properties, likely through inverse regulation of IGF2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In Wilms’ tumor, IGF2‐AS is not only overexpressed but also maintains imprinting and has been shown to generate splice variants that encode putative peptides, suggesting that it may contribute to tumor biology via both RNA‐mediated regulatory mechanisms and peptide production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Beyond oncogenesis, IGF2‐AS influences cell survival in non‐malignant contexts. In neural and retinal cells exposed to cytotoxic stimuli (ketamine and high glucose, respectively), suppression of IGF2‐AS alleviates apoptosis through activation of IGF2/AKT signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Additionally, in trophoblast cells, IGF2‐AS encodes a small peptide (IGF2‐AS‐168aa) that is critical for promoting cell cycle progression and survival, implicating it in placental development and potentially in early pregnancy loss."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, altered serum levels of IGF2‐AS have been observed in HBV‑related hepatocellular carcinoma, indicating its promise as a diagnostic biomarker in this setting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies reveal that IGF2‐AS exerts versatile regulatory effects—ranging from microRNA sponging to modulation of IGF2 signaling and even direct peptide coding—that ultimately influence cell proliferation, apoptosis, migration, and differentiation in a tissue‐ and disease‐specific manner.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ju Huang, You-Xiang Chen, Bo Zhang "}, {"type": "b", "children": [{"type": "t", "text": "IGF2-AS affects the prognosis and metastasis of gastric adenocarcinoma via acting as a ceRNA of miR-503 to regulate SHOX2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastric Cancer (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10120-019-00976-2"}], "href": "https://doi.org/10.1007/s10120-019-00976-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31183590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31183590"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bingxin Liu, Yuhang Liu, Mingyue Zhou, et al. 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