{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA careful review of the provided abstracts reveals that none of these studies mention or discuss HMGA2‐AS1. Instead, these works focus predominantly on the roles of class II phosphoinositide 3‐kinases—particularly the PI3K‐C2α and PI3K‐C2β isoforms—in regulating key cellular processes such as endosomal trafficking, autophagy, vascular development, insulin signaling, platelet production, smooth muscle contraction, and fibrosis. In other words, while these studies greatly enhance our understanding of phosphoinositide 3‐kinase signaling in diverse biological contexts, they do not provide any insight into the function of HMGA2‐AS1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe collective findings of these investigations underscore that the regulatory functions attributed to class II PI3Ks are essential for cellular homeostasis and proper physiological responses in various tissues. Although these enzymes modulate membrane dynamics, signaling cascades, and cytoskeletal organization necessary for processes like angiogenesis, thrombus formation, and muscle contraction, a role for HMGA2‐AS1 was not examined or implicated in any of these studies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, while the abstracts collectively advance our knowledge of PI3K‐C2 family functions in health and disease, they do not offer any data or discussion regarding the biological role of HMGA2‐AS1. Thus, further research will be necessary to delineate if and how HMGA2‐AS1 might interact with or influence these signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marco Falasca, William E Hughes, Veronica Dominguez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2928"}], "href": "https://doi.org/10.1038/nm.2928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22983395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22983395"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kelly Devereaux, Claudia Dall'Armi, Abel Alcazar-Roman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0076405"}], "href": "https://doi.org/10.1371/journal.pone.0076405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24098492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24098492"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tania Maffucci, Marco Falasca "}, {"type": "b", "children": [{"type": "t", "text": "New insight into the intracellular roles of class II phosphoinositide 3-kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20140140"}], "href": "https://doi.org/10.1042/BST20140140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25233418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25233418"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Colin Valet, Gaëtan Chicanne, Childerick Severac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role of class II PI3K-C2α in platelet membrane morphology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2015-03-636670"}], "href": "https://doi.org/10.1182/blood-2015-03-636670"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26109204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26109204"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Barbara Leibiger, Tilo Moede, Meike Paschen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.08.058"}], "href": "https://doi.org/10.1016/j.celrep.2015.08.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26387957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26387957"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Claire Petitjean, Natasha M Setiabakti, Jessica K Mountford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined deficiency of PI3KC2α and PI3KC2β reveals a nonredundant role for PI3KC2α in regulating mouse platelet structure and thrombus stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Platelets (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/09537104.2016.1145202"}], "href": "https://doi.org/10.3109/09537104.2016.1145202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26943229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26943229"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Maria V Selvadurai, Rose J Brazilek, Mitchell J Moon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PI 3-kinase PI3KC2α regulates mouse platelet membrane structure and function independently of membrane lipid composition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13295"}], "href": "https://doi.org/10.1002/1873-3468.13295"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30421419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30421419"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Md Azadul Kabir Sarker, Sho Aki, Kazuaki Yoshioka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Class II PI3Ks α and β Are Required for Rho-Dependent Uterine Smooth Muscle Contraction and Parturition in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2018-00756"}], "href": "https://doi.org/10.1210/en.2018-00756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30476019"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30476019"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jungeun Yu, Naga Suresh Adapala, Laura Doherty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cbl-PI3K interaction regulates Cathepsin K secretion in osteoclasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bone (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bone.2019.07.009"}], "href": "https://doi.org/10.1016/j.bone.2019.07.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31299383"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31299383"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Asma Boukhalfa, Anna Chiara Nascimbeni, Damien Ramel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-14086-1"}], "href": "https://doi.org/10.1038/s41467-019-14086-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31941925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31941925"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Shahidul Islam, Kazuaki Yoshioka, Sho Aki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12576-020-00745-2"}], "href": "https://doi.org/10.1186/s12576-020-00745-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32192434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32192434"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Federico Gulluni, Lorenzo Prever, Huayi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.abk0410"}], "href": "https://doi.org/10.1126/science.abk0410"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34882480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34882480"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Natasha M Setiabakti, Volga Tarlac, Pia Larsson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI3KC2α inhibition is antithrombotic in blood from hypercholesterolemic mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jtha.2023.09.030"}], "href": "https://doi.org/10.1016/j.jtha.2023.09.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37827379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37827379"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Mouin Nasr, Alexis Fay, Adrien Lupieri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PI3KCIIα-Dependent Autophagy Program Protects From Endothelial Dysfunction and Atherosclerosis in Response to Low Shear Stress in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.123.319978"}], "href": "https://doi.org/10.1161/ATVBAHA.123.319978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38152888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38152888"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Song Ling, Doyun Kwak, Yoh Takuwa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discoidin domain receptor 2 signaling through PIK3C2α in fibroblasts promotes lung fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.6253"}], "href": "https://doi.org/10.1002/path.6253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38332727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38332727"}]}]}]}