{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DHRS4‐AS1 is a natural antisense long noncoding RNA that plays multiple roles in both normal gene regulation and disease. In the DHRS4 gene cluster, DHRS4‐AS1 regulates its sense partner and two duplicated homologues (DHRS4L2 and DHRS4L1) via dual mechanisms. In cis, it pairs with the ongoing DHRS4 transcript to recruit chromatin modifiers that mediate deacetylation of histone H3 and demethylation of H3K4, while in trans it interacts with the H3K9‐ and H3K27‐specific histone methyltransferases G9a and EZH2 to deposit repressive marks, and further recruits DNA methyltransferases to induce promoter DNA methylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Transcription of DHRS4‐AS1 itself is enhanced by an adjacent enhancer element that produces an enhancer RNA. This eRNA facilitates DNA looping between the enhancer and the DHRS4‐AS1 promoter, recruits key transcriptional regulators such as RNA polymerase II and p300/CBP, and promotes activating histone modifications, thereby ensuring efficient expression of DHRS4‐AS1 to control the gene cluster economically."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In disease contexts, DHRS4‐AS1 exhibits tumor‐suppressive functions. In hepatocellular carcinoma, lower expression of DHRS4‐AS1 is associated with reduced overall survival, suggesting its loss contributes to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, in lung squamous cell carcinoma, DHRS4‐AS1 participates in a regulatory network by modulating the miR‐423‐5p/LIMK2 axis, thereby influencing prognosis and immune infiltration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In endometriosis, DHRS4‐AS1 functions by sponging miR‐139‐5p, which in turn results in the derepression of ARRDC3; this leads to inhibition of cell proliferation, migration, and invasion along with enhanced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings illustrate that DHRS4‐AS1 serves as a multifunctional regulator: it fine‐tunes the epigenetic landscape of a duplicated gene cluster under physiological conditions and modulates key oncogenic and pathological processes in cancer and other diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Qi Li, Zhongjing Su, Xiaoyuan Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AS1DHRS4, a head-to-head natural antisense transcript, silences the DHRS4 gene cluster in cis and trans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1116597109"}], "href": "https://doi.org/10.1073/pnas.1116597109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22891334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22891334"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yingying Yang, Zhongjing Su, Xuhong Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep20961"}], "href": "https://doi.org/10.1038/srep20961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26864944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26864944"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yongping Zhou, Kuan Li, Xuexia Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA DHRS4-AS1 ameliorates hepatocellular carcinoma by suppressing proliferation and promoting apoptosis via miR-522-3p/SOCS5 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1994719"}], "href": "https://doi.org/10.1080/21655979.2021.1994719"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34666613"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34666613"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yongcheng Su, Beibei Xu, Qianwen Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIMK2 Is a Novel Prognostic Biomarker and Correlates With Tumor Immune Cell Infiltration in Lung Squamous Cell Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2022.788375"}], "href": "https://doi.org/10.3389/fimmu.2022.788375"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35273591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35273591"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xuan Cui, Shisan Zhou, Yongtao Lin "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2060781"}], "href": "https://doi.org/10.1080/21655979.2022.2060781"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35414313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35414313"}]}]}]}