{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GAS6‐AS2 is a long noncoding RNA that has emerged as an important oncogenic regulator in multiple cancer types and in processes related to inflammation. In bladder cancer, elevated GAS6‐AS2 expression correlates with advanced tumor stage and poor prognosis, where it promotes cell proliferation and metastasis by acting as a competitive endogenous RNA (ceRNA) that sponges miR‐298, thereby modulating cell cycle regulators such as CDK9."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In melanoma, increased GAS6‐AS2 levels enhance proliferation and inhibit apoptosis by upregulating GAS6 expression, leading to activation of the AXL/AKT/ERK signaling cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similar oncogenic roles have been suggested in non‐small cell lung cancer, where GAS6‐AS2 is implicated in the regulation of cellular proliferation through interactions with miRNAs such as miR‐144‑3p and signaling mediators like MAPK6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of acute myeloid leukemia, transcriptional activation of GAS6‐AS2 contributes to chemotherapy resistance by hyperactivating the GAS6/TAM pathway, which underscores its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in malignant transformation, GAS6‐AS2 has also been implicated in inflammation-associated processes. For instance, in vascular endothelial cells challenged with inflammatory stimuli, the inhibition of GAS6 expression is mediated by GAS6‐AS2, suggesting that this lncRNA can modulate inflammatory responses and cell–cell interactions through pathways such as Akt/NF‑κB."}, {"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 osteosarcoma, GAS6‐AS2 is upregulated and correlates with advanced clinical stages and poorer survival; mechanistic studies indicate that it promotes proliferation, migration, and invasion while inhibiting apoptosis by sponging miR‑934 to upregulate targets such as BCAT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma, GAS6‐AS2 supports tumor progression by sponging miR‑493‑5p, which leads to increased expression of OTUB1 and subsequent activation of the PI3K/AKT/FoxO3a signaling pathway, thereby enhancing cell proliferation, migration, and invasion while reducing apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings suggest that GAS6‐AS2 functions as an oncogenic lncRNA by acting as a ceRNA to regulate key signaling pathways across diverse tumor types, while also modulating inflammatory responses. Its consistent association with aggressive disease and poor clinical outcomes across cancers makes GAS6‐AS2 a promising prognostic biomarker and a potential therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xin Rui, Li Wang, Huafeng Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GAS6-AS2 promotes bladder cancer proliferation and metastasis via GAS6-AS2/miR-298/CDK9 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13986"}], "href": "https://doi.org/10.1111/jcmm.13986"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30394665"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30394665"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Li Wen, Yuanquan Zheng, Xiaoyi Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of long noncoding RNA GAS6-AS2 promotes proliferation and inhibits apoptosis of melanoma cells via upregulating GAS6 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.2071"}], "href": "https://doi.org/10.1002/iub.2071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31162889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31162889"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Guangjie Hou, Junfeng Yang, Jinxing Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GAS6-AS2 promotes non-small-cell lung cancer cell proliferation via regulating miR-144-3p/ MAPK6 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2020.1867782"}], "href": "https://doi.org/10.1080/15384101.2020.1867782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33459113"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33459113"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Assaf C Bester, Jonathan D Lee, Alejandro Chavez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An Integrated Genome-wide CRISPRa Approach to Functionalize lncRNAs in Drug Resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2018.03.052"}], "href": "https://doi.org/10.1016/j.cell.2018.03.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29677511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29677511"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xuekui Wang, Yingjun Liu, Shengnan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crosstalk between Akt and NF-κB pathway mediates inhibitory effect of gas6 on monocytes-endothelial cells interactions stimulated by P. gingivalis-LPS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.15430"}], "href": "https://doi.org/10.1111/jcmm.15430"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32462812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32462812"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Guojun Wei, Tianwei Zhang, Zongguang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.103015"}], "href": "https://doi.org/10.18632/aging.103015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32269179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32269179"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Cancan Liang, Lan Pang, Yue Ke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA GAS6-AS2 facilitates tumor growth and metastasis of hepatocellular carcinoma by activating the PI3K/AKT/FoxO3a signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31933797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31933797"}]}]}]}