{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe collection of studies provided focuses extensively on the regulation of mitotic spindle assembly, spindle pole focusing, and spindle orientation. Multiple investigations characterize how key mitotic regulators—such as NuMA, p80‐KATNB1, and nucleophosmin/B23—ensure robust anchoring of spindle microtubules at centrosomes and proper kinetochore fiber stabilization. Disruption of these components leads to pronounced defects in spindle structure and function that underlie developmental abnormalities, including congenital brain malformations and leukemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies detail the molecular mechanisms that control mitotic spindle orientation. They describe how the coordinated actions of NuMA, LGN, dynein/dynactin, and emerging regulators like SAPCD2 ensure correct cortical recruitment and stabilization of these proteins during asymmetric cell division. These mechanisms are critical for epithelial stratification, neural progenitor cell behavior, and tissue morphogenesis, with failures in this regulation contributing to defects in cellular differentiation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther reports extend these insights by linking mitotic regulatory pathways with broader cellular processes such as neurogenesis, cytoskeletal dynamics, and intracellular trafficking. For instance, alterations in microtubule organization contribute to axonal growth defects in Huntington’s disease, and interactions with proteins like Galectin‐3 and BRAP2 modulate nucleocytoplasmic cargo localization. Although miRNAs—such as miR‐124—have been implicated in fine‐tuning the expression of mitotic components (e.g., NUMA1), none of the provided abstracts describe the function of MIR4498. Thus, based on the current literature, the biological role and target spectrum of MIR4498 remain undefined, and its potential involvement in regulating cytoskeletal organization or cell division processes awaits future investigation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "M A Sukhai, M Thomas, Y Xuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence of functional interaction between NuMA-RARalpha and RXRalpha in an in vivo model of acute promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2008.106"}], "href": "https://doi.org/10.1038/onc.2008.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18408763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18408763"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Alain D Silk, Andrew J Holland, Don W Cleveland "}, {"type": "b", "children": [{"type": "t", "text": "Requirements for NuMA in maintenance and establishment of mammalian spindle poles."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200810091"}], "href": "https://doi.org/10.1083/jcb.200810091"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19255246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19255246"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Annie Rousselet "}, {"type": "b", "children": [{"type": "t", "text": "Inhibiting Crm1 causes the formation of excess acentriolar spindle poles containing NuMA and B23, but does not affect centrosome numbers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BC20080218"}], "href": "https://doi.org/10.1042/BC20080218"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19522705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19522705"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rebecca G Davies, Kylie M Wagstaff, Eileen A McLaughlin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The BRCA1-binding protein BRAP2 can act as a cytoplasmic retention factor for nuclear and nuclear envelope-localizing testicular proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2013.05.015"}], "href": "https://doi.org/10.1016/j.bbamcr.2013.05.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23707952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23707952"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lindsey Seldin, Nicholas D Poulson, Henry P Foote, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NuMA localization, stability, and function in spindle orientation involve 4.1 and Cdk1 interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-05-0277"}], "href": "https://doi.org/10.1091/mbc.E13-05-0277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24109598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24109598"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lindsey Seldin, Andrew Muroyama, Terry Lechler "}, {"type": "b", "children": [{"type": "t", "text": "NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.12504"}], "href": "https://doi.org/10.7554/eLife.12504"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26765568"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26765568"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Catherine W N Chiu, Carine Monat, Mélanie Robitaille, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2015.12.016"}], "href": "https://doi.org/10.1016/j.devcel.2015.12.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26766442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26766442"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mingyue Jin, Oz Pomp, Tomoyasu Shinoda, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "CircSLC7A2 protects against osteoarthritis through inhibition of the miR-4498/TIMP3 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Prolif (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cpr.13047"}], "href": "https://doi.org/10.1111/cpr.13047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33960555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33960555"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mariacristina Capizzi, Rémi Carpentier, Eric Denarier, et al. 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