{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent advances in understanding Eph receptor and ephrin ligand signaling suggest that MIR5693 may act as a post‐transcriptional regulator modulating these pathways. In developmental contexts, Eph–ephrin interactions are critical for axon guidance and fasciculation – such as ephrin‐B1 regulating peripheral nerve fasciculation via repulsive signaling mediated by EphB2 – and for dynamic regulation of cell migratory behaviors as observed in the primitive streak and early mesoderm."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neural stem/progenitor cells and in pathological conditions of the central nervous system, components of Eph signaling—including EphA receptors functioning in concert with FGFRs—help fine-tune self-renewal versus differentiation, as well as regulate neuroinflammation. Likewise, EphA1 has been implicated in modulating neuroinflammatory cascades and diabetic renal fibrosis via downstream effectors such as MAPK, Rho/ROCK and CXCL12/CXCR4 signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, EphA1 has emerged as a key player in models of neuropathic pain—where its modulation affects pro-inflammatory signaling via the CXCR4/RhoA/ROCK2 pathway—and in oncogenic contexts where its aberrant nuclear localization may contribute to tumor progression. These multifaceted roles hint that MIR5693, if acting to regulate Eph receptor expression or signaling fidelity, could influence diverse outcomes ranging from neural circuit formation and inflammatory responses to pain modulation and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shannon L Duffy, Kirsten A Steiner, Patrick P L Tam, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Trans-Activation between EphA and FGFR Regulates Self-Renewal and Differentiation of Mouse Embryonic Neural Stem/Progenitor Cells via Differential Activation of FRS2α."}]}, {"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.0128826"}], "href": "https://doi.org/10.1371/journal.pone.0128826"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26024354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26024354"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yihui Li, Hongdan Yan, Feng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of EphA1-Epha receptor axis attenuates diabetic nephropathy in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.03.100"}], "href": "https://doi.org/10.1016/j.bbrc.2017.03.100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28341121"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28341121"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jianjun Ma, Zhidong Wang, Siyuan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EphA1 Activation Induces Neuropathological Changes in a Mouse Model of Parkinson's Disease Through the CXCL12/CXCR4 Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-020-02122-x"}], "href": "https://doi.org/10.1007/s12035-020-02122-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33057926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33057926"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ronnie LaCombe, Alessandra Cecchini, Morgan Seibert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EphA1 receptor tyrosine kinase is localized to the nucleus in rhabdomyosarcoma from multiple species."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Open (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/bio.059352"}], "href": "https://doi.org/10.1242/bio.059352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36214254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36214254"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Qi Li, Rui Li, Xiaoxi Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EphA1 aggravates neuropathic pain by activating CXCR4/RhoA/ROCK2 pathway in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-023-00911-9"}], "href": "https://doi.org/10.1007/s13577-023-00911-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37162645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37162645"}]}]}]}