{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>Summary of HOXA‐AS2 Function</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n HOXA‐AS2 is an oncogenic long noncoding RNA that has been reported to play multifaceted roles in the progression of diverse cancers as well as in certain inflammatory conditions. Elevated HOXA‐AS2 expression is associated with increased tumor size, advanced clinical stage, enhanced migration and invasion, and ultimately poor patient prognosis in malignancies such as gastric cancer, papillary thyroid cancer, breast cancer, non‐small cell lung cancer, osteosarcoma, hepatocellular carcinoma, cervical cancer, endometrial cancer, and oral squamous cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistic studies have revealed that HOXA‐AS2 exerts its oncogenic effects through multiple complementary pathways. It modulates cell cycle progression and inhibits apoptosis—effects that are partly mediated by its capacity to epigenetically repress tumor‐suppressive genes (such as P21, PLK3, and DDIT3) by recruiting chromatin‐modifying proteins like EZH2. In addition, HOXA‐AS2 functions as a competing endogenous RNA (ceRNA) by sponging several tumor‐suppressive microRNAs and thereby upregulating oncogenic targets."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " It has also been shown to interact with key signaling pathways—including the Notch and β‐catenin pathways—that further promote malignant phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in cancer, HOXA‐AS2 has been implicated in non‐malignant pathologies. For instance, in sepsis‐induced acute kidney injury, overexpression of HOXA‐AS2 appears to be protective by targeting miR‐106b–5p and suppressing inflammatory signals via the Wnt/β‐catenin and NF‐κB pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In glioma, HOXA‐AS2 modulates intercellular communication—through its interaction with microRNAs such as miR‐885‐5p to regulate targets like RBBP4—and may also influence immune tolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, its involvement in endothelial inflammation has been linked to a negative feedback loop with NF‐κB, suggesting a broader role in regulating inflammatory vascular responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, HOXA‐AS2 acts as a multifaceted regulator that promotes oncogenic cellular behaviors—namely, enhanced proliferation, migration, invasion, and resistance to apoptosis—while also influencing inflammatory responses. These attributes underscore its potential as both a prognostic biomarker and a therapeutic target across a range of cancers and inflammatory disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Min Xie, Ming Sun, Ya-nan Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.5599"}], "href": "https://doi.org/10.18632/oncotarget.5599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26384350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26384350"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Liangfeng Jiang, Zhiming Wu, Xingcheng Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS2 Facilitates Tumorigenesis and Progression of Papillary Thyroid Cancer by Modulating the miR-15a-5p/HOXA3 Axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Gene Ther (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/hum.2018.109"}], "href": "https://doi.org/10.1089/hum.2018.109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30375256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30375256"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yu Fang, Jingxuan Wang, Feng Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA HOXA-AS2 promotes proliferation and invasion of breast cancer by acting as a miR-520c-3p sponge."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.17552"}], "href": "https://doi.org/10.18632/oncotarget.17552"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28545023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28545023"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "T-J Cui, G-S Lin, Y-M Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS2 regulates microRNA-216a-5p to promote malignant progression of non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201908_18656"}], "href": "https://doi.org/10.26355/eurrev_201908_18656"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31389597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31389597"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yihan Wang, Rui Zhang, Guangqi Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA HOXA-AS2 promotes migration and invasion by acting as a ceRNA of miR-520c-3p in osteosarcoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2018.1489174"}], "href": "https://doi.org/10.1080/15384101.2018.1489174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30081707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30081707"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fuqiang Wang, Huili Yang, Zhigang Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000452545"}], "href": "https://doi.org/10.1159/000452545"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27855366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27855366"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qunxiong Wu, Shentao Lu, Li Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Reprod Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s43032-021-00626-y"}], "href": "https://doi.org/10.1007/s43032-021-00626-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34076871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34076871"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhen Zhao, Yan Xing, Fei Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS2 Promotes Oral Squamous Cell Proliferation, Migration, and Invasion via Upregulating EZH2 as an Oncogene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Technol Cancer Res Treat (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/15330338211039109"}], "href": "https://doi.org/10.1177/15330338211039109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34519570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34519570"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jixin Shou, Haidong Gao, Sen Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12935-020-01690-1"}], "href": "https://doi.org/10.1186/s12935-020-01690-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33430870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33430870"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Huifeng Wu, Jing Wang, Zhen Ma "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA HOXA-AS2 mediates microRNA-106b-5p to repress sepsis-engendered acute kidney injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem Mol Toxicol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jbt.22453"}], "href": "https://doi.org/10.1002/jbt.22453"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32048402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32048402"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Chuanhong Zhong, Bei Tao, Xianglong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOXA-AS2 contributes to regulatory T cell proliferation and immune tolerance in glioma through the miR-302a/KDM2A/JAG1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04471-4"}], "href": "https://doi.org/10.1038/s41419-021-04471-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35181676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35181676"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xinxing Zhu, Yanli Liu, Jinjin Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA HOXA-AS2 represses endothelium inflammation by regulating the activity of NF-κB signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2018.12.012"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2018.12.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30658190"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30658190"}]}]}]}