{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLncRNA ZEB2‐AS1 is frequently overexpressed in a wide range of human malignancies—including pancreatic, hepatocellular, gastric, breast, head and neck, colorectal, lung, prostate, and osteosarcoma cancers—where its elevated levels are tightly linked to enhanced tumor cell proliferation, migration, invasion, and resistance to apoptosis. In these studies, high ZEB2‐AS1 expression correlated with aggressive clinicopathological features and poor patient outcomes, underscoring its value as a potential prognostic biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic investigations reveal that ZEB2‐AS1 predominantly functions as a competitive endogenous RNA by sponging specific microRNAs. For example, in pancreatic cancer, ZEB2‐AS1 sequesters miR‐204 to derepress oncogenic HMGB1, while in triple‐negative breast cancer it upregulates ZEB2 via modulation of PI3K/Akt/GSK3β signaling. Similarly, in colorectal cancer its negative regulation of miR‐1205 leads to increased CRKL expression, and in acute myeloid leukemia, sequestering miR‐122‐5p results in PLK1 overexpression. In gastric cancer models, ZEB2‐AS1 positively regulates ZEB2 and further activates the Wnt/β‐catenin pathway, thereby promoting epithelial–mesenchymal transition (EMT) and tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these studies demonstrate that the deregulation of ZEB2‐AS1 critically contributes to tumorigenesis by driving EMT and metastatic processes, as well as by modulating cell cycle and survival pathways. Its aberrant expression is not only a hallmark of advanced disease in several cancers—including gastric, colorectal, breast, lung, and prostate—but also plays an unexpected role in non‐malignant contexts such as pre‐eclampsia, where altered trophoblast proliferation and invasion have been observed. These diverse findings highlight the biological and clinical significance of ZEB2‐AS1, establishing it as a promising candidate for targeted therapeutic intervention and risk stratification in oncology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_fs", "start_ref": "10", "end_ref": "12"}, {"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tian Lan, Lei Chang, Long Wu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The decreased lncRNA ZEB2-AS1 in pre-eclampsia controls the trophoblastic cell line HTR-8/SVneo's invasive and migratory abilities via the miR-149/PGF axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29034"}], "href": "https://doi.org/10.1002/jcb.29034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31148230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31148230"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xu Guo, Yuan Ming Jing, Hai Zhou Lou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect and mechanism of long non-coding RNA ZEB2-AS1 in the occurrence and development of colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Math Biosci Eng (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3934/mbe.2019408"}], "href": "https://doi.org/10.3934/mbe.2019408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31698657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31698657"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yinghao Jiang, Guangming Liu, Wei Ye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZEB2-AS1 Accelerates Epithelial/Mesenchymal Transition Through miR-1205/CRKL Pathway in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biother Radiopharm (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/cbr.2019.3000"}], "href": "https://doi.org/10.1089/cbr.2019.3000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31755734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31755734"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Xiongjian Wu, Haiyan Zhu, Yuan Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of ZEB2-AS1 inhibits cell invasion and induces apoptosis in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J BUON (2020)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32277632"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32277632"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Y-L Li, X-X Zhang, J-N Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZEB2-AS1 regulates the expression of TAB3 and promotes the development of colon cancer by adsorbing microRNA-188."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202004_20998"}], "href": "https://doi.org/10.26355/eurrev_202004_20998"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32373954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32373954"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Hui Xu, Bengtong Yu, Weiyu Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Over-expression of long non-coding RNA ZEB2-AS1 may predict poor prognosis and promote the migration, invasion, and epithelial-mesenchymal transition of tumor cells in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Markers (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1724600820938385"}], "href": "https://doi.org/10.1177/1724600820938385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32611283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32611283"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Jianmin Guan, Ping Liu, Aixia Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non‑coding RNA ZEB2‑AS1 affects cell proliferation and apoptosis via the miR‑122‑5p/PLK1 axis in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2020.4683"}], "href": "https://doi.org/10.3892/ijmm.2020.4683"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32700753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32700753"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jiexiang Yang, Yonggen Zou, Jian Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Long Noncoding RNA ZEB2-AS1 Contributes to Proliferation and Epithelial-to-Mesenchymal Transition of Osteosarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biother Radiopharm (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/cbr.2019.3433"}], "href": "https://doi.org/10.1089/cbr.2019.3433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33085924"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33085924"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Canan Eroğlu Güneş, Ebru Güçlü, Hasibe Vural, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of lncRNA ZEB2NAT suppresses epithelial mesenchymal transition, metastasis and proliferation in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2021.145904"}], "href": "https://doi.org/10.1016/j.gene.2021.145904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34418470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34418470"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Maryam Ahani, Sayyed Mohammad Hossein Ghaderian, Mitra Mehr Azma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential gene expression of BCL-2, ZEB2-AS1 and BALR-2 in prostate cancer and benign prostatic hyperplasia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Andrologia (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/and.14344"}], "href": "https://doi.org/10.1111/and.14344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34866225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34866225"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Mahboobeh Zarei, Kianoosh Malekzadeh, Mahmoud Omidi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical significance of long non-coding RNA ZEB2-AS1 and EMT-related markers in ductal and lobular breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Rep (Hoboken) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cnr2.1826"}], "href": "https://doi.org/10.1002/cnr2.1826"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37088469"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37088469"}]}]}]}