{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZBTB7A—also known as Pokemon or FBI‑1—is a multifunctional transcriptional repressor that modulates key cell‐cycle and tumor suppressor pathways. It can directly bind gene promoters to inhibit the expression of tumor suppressors such as p14ARF, Rb, and p21, thereby promoting cellular transformation and proliferation in several solid tumors including colorectal, prostate, and breast cancers. Overexpression of ZBTB7A in these contexts is associated with aggressive tumor behavior and poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the hematopoietic system and during erythroid maturation, ZBTB7A plays a pivotal regulatory role. It binds directly to fetal globin gene promoters to maintain a repressive chromatin architecture—thereby contributing to the developmental switch from fetal to adult hemoglobin—and recurrent mutations in ZBTB7A have been identified in core‑binding factor acute myeloid leukemia, indicating its involvement in leukemogenesis and lineage fate decisions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in cell‐cycle control, ZBTB7A orchestrates metabolic reprogramming and integrates complex transcriptional networks. It directly represses key glycolytic genes and modulates the activity of other transcription factors—including Sp1, NF‑κB, and SREBP‑1—to influence cellular metabolism, proliferation, and survival. In addition, ZBTB7A has been implicated in the regulation of alternative splicing events, thereby further expanding its impact on the control of gene expression programs essential for both normal physiology and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nZBTB7A also exhibits context‐dependent and multifaceted roles that extend beyond classical transcriptional repression. Alternative RNA processing of the ZBTB7A gene generates a circular RNA (circPOK) that functions independently—and often in opposition—to its linear transcript, thereby highlighting the complexity of its regulation in cancer. In some settings, such as in prostate cancer, ZBTB7A may even exert oncosuppressive effects by antagonizing pro‐invasive transcription factors. Its expression and activity are further fine‐tuned by a variety of noncoding RNAs and microRNAs (for example, miR‑520e, miR‑137, and miR‑125a), which influence chemoresistance, epithelial–mesenchymal transitions, adipocyte differentiation, and immune regulatory functions. In diverse contexts—including lung transplant rejection, metastatic melanoma, and hepatocellular and triple‑negative breast cancers—the diverse roles of ZBTB7A underscore its duality as both an oncogene and a tumor suppressor, with significant therapeutic implications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takahiro Maeda, Robin M Hobbs, Taha Merghoub, et al. 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