{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided studies explicitly mention MIR8053, a synthesis of these findings on profilin 2 (PFN2) and its regulation by microRNAs and interacting proteins suggests that MIR8053 may function as a post‐transcriptional modulator of PFN2. In neurons, PFN2 serves as a key regulator in actin dynamics, influencing neurite outgrowth, synaptic actin polymerization, and receptor trafficking. For example, dysregulated phosphorylation of PFN2a has been linked to impaired neurite extension in spinal muscular atrophy, while distinct PFN2 interactions help fine‐tune synaptic physiology and receptor recycling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its neuronal functions, PFN2 plays roles in diverse cellular systems including cancer, iron metabolism, muscle development, and stem cell biology. Studies demonstrate that PFN2 contributes to membrane trafficking in immune cells and modulates glycolysis and irradiation resistance in breast cancer, while its dysregulation affects myoblast proliferation and apoptosis via p53‐dependent pathways. Moreover, PFN2 levels have been shown to be controlled by iron regulatory proteins and to affect endocytosis and signal transduction in embryonic stem cells. Collectively, these functions support a model in which finely tuned PFN2 expression is essential for coordinating cytoskeletal dynamics and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA recurring theme across these studies is the importance of microRNA‐mediated regulation of PFN2. Although the specific role of MIR8053 is not directly addressed in the provided abstracts, related work—such as the targeting of PFN2 by the miR‐290 family or the modulation of PFN2 levels by miR‐223‐3p in cancer—suggests that a microRNA like MIR8053 could similarly influence PFN2 expression. By repressing PFN2, MIR8053 might indirectly regulate actin polymerization, cytoskeletal reorganization, and membrane dynamics, thereby impacting neuronal plasticity, cell motility, and differentiation. Furthermore, such regulation could have broad implications for pathologies ranging from neurodegenerative diseases to cancer and developmental disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anna Nölle, Andre Zeug, Jeroen van Bergeijk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The spinal muscular atrophy disease protein SMN is linked to the Rho-kinase pathway via profilin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr425"}], "href": "https://doi.org/10.1093/hmg/ddr425"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21920940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21920940"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pietro Pilo Boyl, Alessia Di Nardo, Christophe Mulle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601737"}], "href": "https://doi.org/10.1038/sj.emboj.7601737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17541406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17541406"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ralph Gareus, Alessia Di Nardo, Vladimir Rybin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mouse profilin 2 regulates endocytosis and competes with SH3 ligand binding to dynamin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M503528200"}], "href": "https://doi.org/10.1074/jbc.M503528200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16319076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16319076"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Petri Kursula, Inari Kursula, Marzia Massimi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High-resolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: the formin homology 1 domain of mDia1 and the proline-rich domain of VASP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2007.10.050"}], "href": "https://doi.org/10.1016/j.jmb.2007.10.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18001770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18001770"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Andreas Birbach, J Martin Verkuyl, Andrew Matus "}, {"type": "b", "children": [{"type": "t", "text": "Reversible, activity-dependent targeting of profilin to neuronal nuclei."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2006.03.026"}], "href": "https://doi.org/10.1016/j.yexcr.2006.03.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16716297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16716297"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stefanie K Schweinhuber, Tania Meßerschmidt, Robert Hänsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Profilin isoforms modulate astrocytic morphology and the motility of astrocytic processes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0117244"}], "href": "https://doi.org/10.1371/journal.pone.0117244"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25629407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25629407"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Marina Di Domenico, Melanie Jokwitz, Walter Witke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specificity and Redundancy of Profilin 1 and 2 Function in Brain Development and Neuronal Structure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells10092310"}], "href": "https://doi.org/10.3390/cells10092310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34571959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34571959"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Magali Mondin, Mario Carta, Elisabeth Normand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Profilin II regulates the exocytosis of kainate glutamate receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.140442"}], "href": "https://doi.org/10.1074/jbc.M110.140442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20937818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20937818"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Tao Ni, Fang Jiao, Xiulian Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.aax8286"}], "href": "https://doi.org/10.1126/sciadv.aax8286"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32064340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32064340"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yue Zhao, Rui Zhong, Chaoyue Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circle RNA circABCB10 Modulates PFN2 to Promote Breast Cancer Progression, as Well as Aggravate Radioresistance Through Facilitating Glycolytic Metabolism Via miR-223-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biother Radiopharm (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/cbr.2019.3389"}], "href": "https://doi.org/10.1089/cbr.2019.3389"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32522014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32522014"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sara Luscieti, Bruno Galy, Lucia Gutierrez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The actin-binding protein profilin 2 is a novel regulator of iron homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2016-11-754382"}], "href": "https://doi.org/10.1182/blood-2016-11-754382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28774878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28774878"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Huaqin Li, Lianjie Hou, Yu Zhang, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PFN2a"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Suppresses C2C12 Myogenic Development by Inhibiting Proliferation and Promoting Apoptosis via the p53 Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells8090959"}], "href": "https://doi.org/10.3390/cells8090959"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31450751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31450751"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Alison P Casserly, Junko Tsuji, Rubing Zhao-Shea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated miRNA-/mRNA-Seq of the Habenulo-Interpeduncular Circuit During Acute Nicotine Withdrawal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-57907-w"}], "href": "https://doi.org/10.1038/s41598-020-57907-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31965003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31965003"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Carolyn Sangokoya, Robert Blelloch "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-dependent inhibition of PFN2 orchestrates ERK activation and pluripotent state transitions by regulating endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2002750117"}], "href": "https://doi.org/10.1073/pnas.2002750117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32788350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32788350"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Pratibha Verma, Smita Yevate, Jeeva S E, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of Profilin 2 on HDAC6 overexpression in mouse GC-1 cells and its putative role in germ cell migration in the testis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Tissue Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00441-023-03755-9"}], "href": "https://doi.org/10.1007/s00441-023-03755-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36788143"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36788143"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Petoria Gayle, Vanessa McGaughey, Rosmely Hernandez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Maternal- and Fetal-Encoded Perforin-2 Limits Placental Infection by a Bloodborne Pathogen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.2000615"}], "href": "https://doi.org/10.4049/jimmunol.2000615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32839236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32839236"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Dina Andriamoratsiresy, Aleksandr Piskunov, Regis Lutzing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PFN2a, a new partner of RARα in the cytoplasm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.11.096"}], "href": "https://doi.org/10.1016/j.bbrc.2017.11.096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29158086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29158086"}]}]}]}