{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMEIS2 is a highly conserved TALE‐class homeodomain transcription factor that plays a critical role in normal development by acting as a cofactor with HOX proteins and orchestrating gene‐regulatory networks across multiple organ systems. In the developing brain, for example, MEIS2 expression is tightly controlled—partly through microRNA‐dependent mechanisms—to influence neural progenitor proliferation and differentiation, and in the developing neocortex and ganglionic eminence its spatial–temporal expression appears to be important for proper regional specification. In parallel, disruptions of MEIS2 by deletions or nucleotide‐level variants have been linked to congenital anomalies that include cleft palate, cardiac septal defects, and intellectual disability. Furthermore, studies in human cardiomyocyte progenitor cells reveal that MEIS2 is targeted by specific microRNAs to modulate cell cycle gene expression and cardiac chamber identity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its developmental functions, MEIS2 plays multifaceted roles in oncogenesis. In various cancers—including neuroblastoma, acute myeloid leukemia, prostate, bladder, colorectal, thyroid, and possibly breast cancer—MEIS2 serves as a transcriptional activator of cell‐cycle and mitotic genes. Its activity can promote tumor cell proliferation and survival in certain contexts (as seen in neuroblastoma and AML where MEIS2 supports the expression of a network of late cell‐cycle genes), while in other settings sustained MEIS2 expression has been associated with less aggressive or more indolent tumor phenotypes. Moreover, alternative splicing of MEIS2 gives rise to isoforms with opposing functions that modulate cell fate decisions, metastatic potential, chemoresistance, and even metabolic responses to drugs; MEIS2’s interactions with other transcription factors (for example, with Klf4 or AML1‐ETO) further refine its role in tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also underscores the therapeutic potential of targeting MEIS2. For example, approaches that silence MEIS2 in adult cardiomyocytes have been shown to promote cell cycle reentry and improve cardiac function following ischemic injury, highlighting a promising strategy for cardiac regeneration. Collectively, these findings reveal that MEIS2 functions as a pivotal regulator bridging developmental processes, cellular identity, and disease progression—with its tight regulation opening new avenues for targeted intervention in congenital disorders and cancer alike."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bei Xu, Dirk Geerts, Kun Qian, et al. 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