{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HOXD‐AS2 is an oncogenic long non‐coding RNA that has been implicated in several cancer types, most notably in glioblastoma and lung adenocarcinoma. In glioma, HOXD‐AS2 is markedly upregulated and its overexpression is associated with higher tumor grade and poor prognosis. Functional studies have demonstrated that silencing HOXD‐AS2 suppresses cell proliferation, migration, and invasion, while promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, HOXD‐AS2 contributes to the reorganization of chromatin architecture of the HOXD locus in glioma cells. Acting in concert with another lncRNA, LINC01116, HOXD‐AS2 facilitates CTCF/cohesin‐mediated looping that results in coactivation of miR‐10b and multiple HOXD genes, thus promoting neoplastic transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, HOXD‐AS2 has been implicated in chemoresistance mechanisms. In glioblastoma cells treated with temozolomide, TGF‐β/Smad signaling upregulates HOXD‐AS2 along with H19, leading to competitive binding with the RNA‐binding protein KSRP and preventing the maturation of miR‐198. The resulting decrease in miR‐198 levels causes an increase in MGMT expression, thereby promoting temozolomide resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in lung adenocarcinoma, ceRNA network analyses suggest that HOXD‐AS2 may act as a molecular sponge that contributes to cisplatin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, differential expression patterns of HOXD‐AS2 in normal tissues further underscore its potential role in tissue‐specific regulation. For example, in normal colorectal mucosa, HOXD‐AS2 is expressed at significantly higher levels in the sigmoid colon compared with the rectum, suggesting that the HOXD cluster, including HOXD‐AS2, may participate in regional gene expression programs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the multifaceted role of HOXD‐AS2 in promoting tumor progression, mediating chemoresistance, and influencing chromatin architecture and tissue‐specific gene expression. Its oncogenic functions and regulatory interactions underscore its potential as a diagnostic marker and therapeutic target in various cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xingming Zhong, Yong Cai "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA (lncRNA) HOXD-AS2 promotes glioblastoma cell proliferation, migration and invasion by regulating the miR-3681-5p/MALT1 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1977104"}], "href": "https://doi.org/10.1080/21655979.2021.1977104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34802389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34802389"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yingjiao Qi, Zhixing Wang, Fan Wu, et al. 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