{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn numerous human cancers, SOX21‑AS1 is frequently overexpressed and functions as a potent oncogene. In cervical cancer, triple‑negative breast cancer, lung adenocarcinoma, non‑small cell lung cancer, breast cancer stem cells, glioma and other malignancies, SOX21‑AS1 promotes cell proliferation, migration, invasion, and stemness. Mechanistically, it acts primarily as a competing endogenous RNA that sponges distinct microRNAs—including miR‑7, miR‑520a‑5p, miR‑24‑3p, miR‑144‑3p, and miR‑9‑3p—to upregulate downstream targets such as VDAC1, ORMDL3, PIM2, TSPAN8, and PAK7. In doing so, it modulates multiple signaling pathways (e.g., Hippo, Wnt, ERK, and PI3K/AKT) and contributes to chemoresistance via epithelial‑to‑mesenchymal transition regulation and altered promoter methylation states."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSOX21‑AS1 is also implicated in neurodegenerative conditions. In models of Alzheimer’s disease and amyloid‑β–induced neuronal injury, as well as in Parkinson’s disease, elevated SOX21‑AS1 levels contribute to neuronal damage by increasing apoptosis, oxidative stress, and inflammatory responses. Silencing SOX21‑AS1 alleviates these deleterious effects by restoring the activity of protective signaling cascades (including PI3K/AKT) through modulation of microRNAs such as miR‑132 and miR‑7‑5p."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPreliminary evidence also suggests that SOX21‑AS1 may be involved in the progression of pancreatic cancer and osteosarcoma, though its functional roles in these diseases remain less well characterized. Early studies point to a potential contribution to tumor malignancy, indicating that further investigation into SOX21‑AS1–mediated regulatory networks across a broader range of cancers is warranted."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiaoyan Zhang, Xianlan Zhao, Yan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA SOX21-AS1 promotes cervical cancer progression by competitively sponging miR-7/VDAC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.28371"}], "href": "https://doi.org/10.1002/jcp.28371"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30912129"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30912129"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "S Y Gai, Z H Yuan "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA SOX21-AS1 promotes cell proliferation and invasion through upregulating PAK7 expression by sponging miR-144-3p in glioma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2020_190509N412"}], "href": "https://doi.org/10.4149/neo_2020_190509N412"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31973536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31973536"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xia Liu, Jingyong Song, Yu Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA SOX21-AS1 regulates the progression of triple-negative breast cancer through regulation of miR-520a-5p/ORMDL3 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.29674"}], "href": "https://doi.org/10.1002/jcb.29674"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32277517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32277517"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yan Xu, Hongwei Wu, Lin Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of long non-coding RNA SOX21-AS1 inhibits lung adenocarcinoma invasion and migration by impairing TSPAN8 via transcription factor GATA6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Macromol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijbiomac.2020.07.172"}], "href": "https://doi.org/10.1016/j.ijbiomac.2020.07.172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32698071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32698071"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Peipei Du, Yanfang Zhi, Ruijie Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant Methylation of the SOX21-AS1 Promoter Region Promotes Gene Expression and Its Clinical Value in Cervical Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s43032-020-00335-y"}], "href": "https://doi.org/10.1007/s43032-020-00335-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33095426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33095426"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lanzhen Li, Dongmei Meng, Ruiqing Wang "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA SOX21-AS1 enhances the stemness of breast cancer cells via the Hippo pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Open Bio (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/2211-5463.13015"}], "href": "https://doi.org/10.1002/2211-5463.13015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33103351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33103351"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Fengfeng Wang, Tengfei Gu, Yao Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA SOX21-AS1 modulates lung cancer progress upon microRNA miR-24-3p/PIM2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1955578"}], "href": "https://doi.org/10.1080/21655979.2021.1955578"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34511042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34511042"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jing Tian, Ze Li, Yuanyuan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SOX21-AS1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Alleviated Cisplatin Resistance in Cervical Cancer Through Epithelial-Mesenchymal Transition Inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Rejuvenation Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/rej.2022.0009"}], "href": "https://doi.org/10.1089/rej.2022.0009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36039935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36039935"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zhengyu Lu, Jin Xu, Binhao Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA SOX21-AS1: A potential tumor oncogene in human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2023.154774"}], "href": "https://doi.org/10.1016/j.prp.2023.154774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37633003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37633003"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Wanru Xu, Kai Li, Qian Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of long non-coding RNA SOX21-AS1 attenuates amyloid-β-induced neuronal damage by sponging miR-107."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20194295"}], "href": "https://doi.org/10.1042/BSR20194295"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32124921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32124921"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yang Xie, Shujiang Zhang, Zhiyu Lv, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX21-AS1 modulates neuronal injury of MMP"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-treated SH-SY5Y cells via targeting miR-7-5p and inhibiting IRS2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2020.135602"}], "href": "https://doi.org/10.1016/j.neulet.2020.135602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33421490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33421490"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Fengming Gu, Daofei Ji, Hongzao Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SRY-Box 21 Antisense RNA 1 Knockdown Diminishes Amyloid Beta"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "25-35"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "-Induced Neuronal Damage by miR-132/PI3K/AKT Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11064-021-03373-3"}], "href": "https://doi.org/10.1007/s11064-021-03373-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34146195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34146195"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Huiping Chen, Juan Chen "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA SOX21-AS1 Promotes the Growth and Invasiveness of Osteosarcoma Cells Through miR-7-5p/IRS2 Regulatory Network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Med Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arcmed.2020.11.007"}], "href": "https://doi.org/10.1016/j.arcmed.2020.11.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33341286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33341286"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Dandan Yu, Zhigang Zhao, Li Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SOX21-AS1 activated by STAT6 promotes pancreatic cancer progression via up-regulation of SOX21."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-022-03521-5"}], "href": "https://doi.org/10.1186/s12967-022-03521-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36335356"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36335356"}]}]}]}