{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZBED3 is a novel modulator of the canonical Wnt/β-catenin signaling pathway. Initial studies revealed that ZBED3 directly interacts with the scaffold protein Axin through a conserved, phosphorylation‐dependent PPPPSPT motif. This interaction disrupts the recruitment of kinases required for β-catenin degradation, thereby facilitating β-catenin accumulation and subsequent transcriptional activation of downstream genes. In non‐small cell lung cancer, overexpression of ZBED3 is correlated with increased cell proliferation and invasion, and mutational analyses indicate that its BED finger domain is critical not only for β-catenin regulation but also for the expression of proliferation‐associated proteins such as PCNA."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in Wnt signaling, ZBED3 has been implicated in metabolic regulation and stem cell differentiation. Genome-wide association studies and related investigations have connected ZBED3 with insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, suggesting a broader function in energy homeostasis. Moreover, in the realm of regenerative medicine, the long noncoding RNA ZBED3-AS1 has been shown to promote chondrogenesis in human synovial fluid-derived mesenchymal stem cells by directly upregulating zbed3 expression and activating Wnt/β-catenin signaling, thereby enhancing cartilage formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nZBED3’s oncogenic potential extends to other malignancies through distinct regulatory networks. In hepatocellular carcinoma, NSUN5—an RNA 5-methylcytosine methyltransferase—upregulates ZBED3, which in turn counteracts the tumor-suppressive regulation of the Wnt/β-catenin pathway. Similarly, in breast cancer, downregulation of the divergent noncoding RNA ZBED3-AS1 leads to deregulation of the miR-513a-5p/KLF6 axis, while in gastric cancer, a circular RNA (hsa_circ_0119412) acts as a sponge for miR-1298-5p to modulate ZBED3 expression, with significant impacts on cell viability, apoptosis, and invasion. These findings underscore the multifaceted roles of ZBED3 in diverse pathological processes ranging from metabolic disorders to various cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ting Chen, Meng Li, Yu Ding, et al. 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