{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HNF4A‐AS1, a long noncoding RNA originating from the HNF4A locus, has emerged as a multifaceted regulator of transcriptional and metabolic programs in diverse disease settings. In the gastrointestinal tract, reduced expression of HNF4A‐AS1 is associated with impaired epithelial metabolic signatures observed in inflammatory conditions such as pediatric Crohn’s disease, suggesting a role in maintaining epithelial homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In neuroblastoma, HNF4A‐AS1 has been shown to encode a small 51–amino acid peptide (sPEP1) that enhances cancer stem cell self‐renewal and aggressiveness by modulating key translation initiation and elongation factors, thereby repressing SMAD4‐mediated transactivation and driving the expression of stem cell–related genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In a related study focusing on metabolic reprogramming, HNF4A‐AS1 was found to promote aerobic glycolysis in neuroblastoma by binding to hnRNPU and facilitating its interaction with the transcription factor CTCF, resulting in altered transcription of HNF4A and other tumor‐promoting genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, in the context of drug‐induced hepatotoxicity, HNF4A‐AS1 modulates the expression of cytochrome P450 enzymes by influencing the binding of the pregnane X receptor (PXR) and altering histone modification patterns at the CYP3A4 promoter, thereby impacting the liver’s susceptibility to injury from agents such as ritonavir."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, HNF4A‐AS1 plays a critical role in the isoform‐specific regulation of HNF4α during development and carcinogenesis in digestive tissues, contributing to the dynamic balance between the adult (P1) and fetal (P2) isoforms of HNF4α."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings reveal that HNF4A‐AS1 integrates metabolic, proliferative, and stress–response pathways in a context‐dependent manner, highlighting its potential as both a biomarker and a therapeutic target in inflammatory diseases, cancer, and drug–induced liver injury.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yael Haberman, Marina BenShoshan, Ayelet Di Segni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflamm Bowel Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/ibd/izx013"}], "href": "https://doi.org/10.1093/ibd/izx013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29361088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29361088"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Huajie Song, Jianqun Wang, Xiaojing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HNF4A-AS1-encoded small peptide promotes self-renewal and aggressiveness of neuroblastoma stem cells via eEF1A1-repressed SMAD4 transactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-022-02271-4"}], "href": "https://doi.org/10.1038/s41388-022-02271-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35318442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35318442"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Huajie Song, Dan Li, Xiaojing Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HNF4A-AS1/hnRNPU/CTCF axis as a therapeutic target for aerobic glycolysis and neuroblastoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hematol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13045-020-00857-7"}], "href": "https://doi.org/10.1186/s13045-020-00857-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32216806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32216806"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaofei Wang, Yihang Yu, Pei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long Noncoding RNAs Hepatocyte Nuclear Factor 4A Antisense RNA 1 and Hepatocyte Nuclear Factor 1A Antisense RNA 1 Are Involved in Ritonavir-Induced Cytotoxicity in Hepatoma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Metab Dispos (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/dmd.121.000693"}], "href": "https://doi.org/10.1124/dmd.121.000693"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34949673"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34949673"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shangdong Guo, Hong Lu "}, {"type": "b", "children": [{"type": "t", "text": "Novel mechanisms of regulation of the expression and transcriptional activity of hepatocyte nuclear factor 4α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.27407"}], "href": "https://doi.org/10.1002/jcb.27407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30191603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30191603"}]}]}]}