{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The long non‐coding RNA GAS8‐AS1 (also known as C16orf3) has emerged as a multifaceted tumor suppressor that is frequently altered in several human diseases, particularly in various cancers. In papillary thyroid carcinoma (PTC), comprehensive exome‐sequencing studies revealed that GAS8‐AS1 is one of the most frequently mutated genes; a hotspot dinucleotide substitution (c.713A>G/714T>C) was linked to advanced disease, and the wild‐type transcript showed a stronger ability to suppress cancer cell growth than the mutated form."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, GAS8‐AS1 has been demonstrated to inhibit proliferation and cell cycle progression by modulating key downstream targets, including Cyclin G2 via interaction with miR‐135b–5p in PTC cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and by promoting autophagy through upregulation of ATG5 and ATG7 via miRNA‐mediated pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In other malignancies, GAS8‐AS1 exerts similar tumor suppressive functions. In colorectal cancer, its overexpression leads to the downregulation of the oncogenic lncRNA AFAP1‐AS1, thereby inhibiting cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In osteosarcoma, reduced GAS8‐AS1 levels correlate with poor patient survival, whereas its overexpression decreases UCA1 expression, suppressing cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in glioblastoma, GAS8‐AS1 downregulates NEAT1, leading to decreased proliferation and invasion along with dampening of the Wnt/β‐catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in solid tumors, GAS8‐AS1 has also been implicated in non‐malignant conditions. For instance, its elevated expression in peripheral blood has been associated with relapsing–remitting multiple sclerosis, suggesting potential as a diagnostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " A recent review further summarized that GAS8‐AS1 modulates several biological functions—including proliferation, migration, invasion, and autophagy—by interacting with diverse signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic profiling studies in PTC have also revealed a spectrum of GAS8‐AS1 alterations that are associated with tumor stage, multifocality, and serum thyroid‐stimulating hormone levels, emphasizing its potential utility in diagnostic screening and prognostic evaluation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In gastric cancer, GAS8‐AS1 acts as a tumor suppressor by downregulating miR‐21‐3p, thereby inhibiting cell proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and circulating levels of GAS8‐AS1 have been shown to distinguish thyroid cancer from benign nodular goiters with notable accuracy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Additionally, in gastric tissues, while GAS8 is significantly downregulated, GAS8‐AS1 expression appears elevated in tumors with lymphatic or vascular invasion, suggesting a complex interplay in tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " In ovarian cancer, decreased GAS8‐AS1 expression correlates with poorer survival, and mechanistic studies have shown that GAS8‐AS1 inhibits cancer progression by binding to Beclin1 to activate autophagy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, earlier work characterizing the genomic region harboring GAS8 and its antisense transcript (GAS8‐AS1) has reinforced the notion of a tumor suppressor role within this locus, even though mutational analyses in some cancers (e.g., breast cancer) did not reveal significant differences between tumor and non‐tumor tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, GAS8‐AS1 plays an important tumor suppressor role by modulating cell proliferation, cell cycle progression, migration, invasion, and autophagy through various molecular mechanisms—often via interactions with microRNAs and key signaling molecules. Its frequent alteration in cancers, along with its diagnostic and prognostic potential, highlights GAS8‐AS1 as a promising biomarker and a possible therapeutic target across multiple human malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wenting Pan, Liqing Zhou, Minghua Ge, et al. 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