{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSMC4 is a core subunit of the condensin complex—a chromosomal ATPase essential for maintaining chromosome architecture, condensation, and accurate segregation during mitosis. Structural studies have revealed that SMC4 participates in heterodimer formation with its partner subunit and provides a unique binding surface for single‐stranded DNA, thereby underpinning its pivotal role in genome organization and stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant SMC4 expression has been implicated in the progression of numerous malignancies. Elevated SMC4 levels correlate with aggressive tumor characteristics—as seen in primary liver cancer, where its overexpression is associated with increased tumor size, de-differentiation, advanced stage, and vascular invasion. In colorectal cancer, SMC4 has been identified as a putative tumorigenesis gene, with evidence showing that its mRNA is targeted by miR-124-5p; however, its full contribution to colorectal tumor development remains under investigation. Moreover, upregulated SMC4 expression is also reported in acute myeloid leukemia, breast cancer, glioma, endometrial cancer, bladder cancer, cardia adenocarcinoma, and ovarian cancer, where it promotes enhanced cell proliferation, migration, and resistance to apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical mitotic functions, SMC4 plays an integral role in modulating cell cycle progression and orchestrating inflammatory responses. Under hypoxic conditions, for instance, SMC4 is transcriptionally upregulated via a HIF-1-dependent pathway and concurrently modulated by miR-219, leading to G1 phase arrest release and promoting epithelial–mesenchymal transition in hepatocellular carcinoma. In parallel, SMC4 is functionally linked to innate immunity; its interaction with TREM-1 enhances NLRP3 inflammasome activation and cardiomyocyte pyroptosis in sepsis, while it also facilitates proinflammatory cytokine production by recruiting histone acetylation complexes to the nemo promoter to boost NEMO transcription."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria Francisca Ham, Tetsuya Takakuwa, Nur Rahadiani, et al. 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