{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ING5, a member of the Inhibitor of Growth family, functions as a multifaceted regulator of cellular homeostasis by modulating key processes such as cell cycle progression, apoptosis, chromatin remodeling, and differentiation. Initially identified as a gene whose over‐expression promotes p53 acetylation and p21 activation to inhibit colony formation and induce apoptosis, ING5 serves an important role in p53‐dependent tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, ING5 is an integral subunit of histone acetyltransferase (HAT) complexes – including the MOZ/MORF and HBO1 assemblies – where its plant homeodomain mediates recognition of specific histone marks and thereby enhances acetylation of nucleosomal substrates, ultimately influencing gene transcription."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Regulation of ING5 expression is critical for maintaining normal cellular growth. MicroRNAs such as miR-193 and miR-1307 suppress ING5 levels, thereby promoting cell proliferation and chemoresistance in mesenchymal stem cells and ovarian or bladder cancer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Consistent with its tumor-suppressive functions, reduced nuclear expression or aberrant cytoplasmic localization of ING5 is frequently observed in gastric, colorectal, and head and neck carcinomas, correlating with enhanced tumor growth, invasiveness and poor clinical outcome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In lung cancer models, ING5 overexpression inhibits epithelial–mesenchymal transition and tumor cell invasion, partly by promoting β‐catenin phosphorylation and degradation, reinforcing its role as a negative regulator of oncogenic signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Similarly, in leukemia and other solid tumors, ING5 interacts with factors such as INCA1 to impose cell cycle arrest and enhance apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Conversely, in glioblastoma, ING5 may enhance stem cell marker expression, self-renewal, and activate proliferative signaling pathways – highlighting that its function may be context-dependent."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Furthermore, recent studies implicate ING5 in cardiomyocyte proliferation during myocardial repair through engagement of the ING5/P21 signaling axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", reinforcing its diverse regulatory roles in both normal physiology and cancer biology.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, the critical impact of ING5 on chromatin dynamics and gene expression is further underscored by its involvement in complexes that modify histone acetylation patterns, thereby controlling transcriptional programs that determine cell fate decisions"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "). Collectively, these studies demonstrate that ING5 operates as an important epigenetic and cell cycle regulator whose expression and subcellular localization determine diverse outcomes—ranging from tumor suppression and chemosensitivity to, under particular conditions, enhanced stemness—thereby making it a promising target for therapeutic intervention in various human cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masayuki Shiseki, Makoto Nagashima, Remy M Pedeux, et al. 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