{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAge-related macular degeneration (AMD) is closely linked to hypoxia-driven changes in retinal pigment epithelial (RPE) cells, where a tightly regulated genetic network controls responses to oxygen deprivation. Recent findings in human ARPE-19 cells reveal that the long non-coding RNA HDAC4-AS1 is markedly upregulated under hypoxic conditions, while its expression returns toward baseline upon re-oxygenation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " \n<br><br>\nMechanistic investigations showed that under hypoxic stress, HDAC4-AS1 actively modulates the transcriptional behavior of its sense gene, HDAC4. Specifically, HDAC4-AS1 binds to the HDAC4 promoter region and promotes the recruitment of HIF-1α, a transcription factor critical for the hypoxic response. This interaction is further underscored by experiments in which HDAC4-AS1 knockdown led to a suppression of HDAC4 promoter activity exclusively in hypoxic conditions"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n<br><br>\nCollectively, these results suggest that HDAC4-AS1 functions as a fine-tuner of hypoxia-induced transcriptional responses in RPE cells by negatively regulating HDAC4 expression via HIF-1α recruitment. This insight not only broadens our understanding of the molecular underpinnings of hypoxia in retinal pathophysiology but also provides a promising molecular target for novel therapeutic interventions in AMD."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jie Pan, Luxin Zhao "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2021.1933821"}], "href": "https://doi.org/10.1080/21655979.2021.1933821"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34057022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34057022"}]}]}]}