{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nResearch in breast biology has revealed that the long noncoding RNA originally designated Zfas1 (the human ortholog being ZFAS1) plays an important role in mammary gland development. In vivo, high expression of this lncRNA in the ducts and alveoli of the mammary gland, along with its ability to modulate cell proliferation and differentiation, lends support to its putative tumor‐suppressive function in breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cardiovascular system, ZFAS1 has emerged as a significant regulator of cardiac function. Studies have demonstrated that this lncRNA acts as an inhibitor of SERCA2a, a crucial Ca²⁺ pump in the sarcoplasmic reticulum, thereby provoking intracellular Ca²⁺ overload. This dysregulation contributes to myocardial contractile dysfunction and accentuates cardiomyocyte apoptosis in both acute myocardial infarction and hypoxia/reoxygenation injury models. In addition, ZFAS1 is implicated in sepsis‐induced cardiac dysfunction wherein it modulates pyroptosis and autophagy, further highlighting its pathogenic impact on cardiac tissue under stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these systems, ZFAS1 has been shown to modulate diverse biological processes in several tissues. In bone and mesenchymal stem cell biology, for example, aberrant ZFAS1 expression influences the balance between osteogenic and adipogenic differentiation of BMSCs via a regulatory axis involving miR‐499 and EPHA5, potentially contributing to osteoporotic bone loss. In neurological settings, upregulation of ZFAS1 is associated with exacerbated apoptosis and inflammation in spinal cord injury through interactions with miR‐1953 and downstream modulation of the PTEN/PI3K/AKT pathway. Moreover, in the context of cerebral and pulmonary ischemia–reperfusion injuries, exosomal transfer of ZFAS1 from bone marrow mesenchymal stem cells appears to confer protection by altering mRNA decay pathways and inactivating pro‐inflammatory drivers. In pancreatic cancer, metabolic stress induces ZFAS1 overexpression which, in turn, promotes the epithelial–mesenchymal transition and metastasis via enhanced stabilization of ZEB1. Finally, emerging roles in allergic rhinitis and Fuchs endothelial corneal dystrophy suggest that ZFAS1 is involved in regulating cell death and inflammatory cascades across various tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to the extensively studied lncRNA ZFAS1, one study specifically investigated the zinc finger transcription factor ZNF528 in the context of bone disorders. In a family with severe primary osteoporosis—where a COL1A2 haploinsufficiency was present—a rare nonsense variant in ZNF528 was identified. This mutation results in the production of a truncated ZNF528 protein that, while retaining its ability to localize to the nucleus, displays a global shift in genomic binding. Such altered occupancy over regulatory DNA elements suggests that ZNF528 normally functions as a transcriptional regulator of genes critical for bone morphology. The variant-induced changes in target gene expression likely contribute to the severe osteoporotic phenotype seen in these patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marjan E Askarian-Amiri, Joanna Crawford, Juliet D French, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.2528811"}], "href": "https://doi.org/10.1261/rna.2528811"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21460236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21460236"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ying Zhang, Lei Jiao, Lihua Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ZFAS1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " as a SERCA2a Inhibitor to Cause Intracellular Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.117.312117"}], "href": "https://doi.org/10.1161/CIRCRESAHA.117.312117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29475982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29475982"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lei Jiao, Mengmeng Li, Yingchun Shao, et al. 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