{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMembers of the glycerophosphodiester phosphodiesterase family have emerged as key regulators of cell differentiation and surface remodeling in multiple tissues. For instance, studies in osteoblast-like cells have shown that GDE3, a seven‐transmembrane protein with extracellular catalytic activity, drives matrix maturation and promotes dramatic morphological changes via actin cytoskeleton reorganization, leading to enhanced alkaline phosphatase activity and calcium deposits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, GDE3 has been implicated in negative regulation of cell invasion by acting as a GPI‐specific phospholipase C that cleaves the urokinase receptor (uPAR) from the surface of breast cancer cells, thereby dampening pro‐migratory and matrix‐degrading signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in the central nervous system, GDE3 mediates the release of the CNTF receptor component (CNTFRα) to modulate oligodendrocyte precursor cell proliferation and differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in the airways, elevated nitric oxide levels trigger upregulation of Gdpd2—another glycerophosphodiester phosphodiesterase family member—to influence club cell apoptosis, cell cycle progression, and differentiation during severe asthma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these enzyme‐mediated mechanisms, microRNA miR‑5692a has been implicated specifically in hepatocellular carcinoma, where its dysregulated expression appears to contribute to tumor progression. Although its precise molecular targets and mechanisms remain to be fully elucidated, the study suggests that miR‑5692a may modulate crucial signaling pathways that govern cellular proliferation and differentiation, potentially intersecting with the regulatory networks highlighted for glycerophosphodiester phosphodiesterases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Noriyuki Yanaka, Yuji Imai, Eri Kawai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel membrane protein containing glycerophosphodiester phosphodiesterase motif is transiently expressed during osteoblast differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M302867200"}], "href": "https://doi.org/10.1074/jbc.M302867200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12933806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12933806"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daniela Corda, Takahiro Kudo, Pasquale Zizza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The developmentally regulated osteoblast phosphodiesterase GDE3 is glycerophosphoinositol-specific and modulates cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.035444"}], "href": "https://doi.org/10.1074/jbc.M109.035444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19596859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19596859"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michiel van Veen, Elisa Matas-Rico, Koen van de Wetering, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.23649"}], "href": "https://doi.org/10.7554/eLife.23649"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28849762"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28849762"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Mateusz Dobrowolski, Clinton Cave, Reuben Levy-Myers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.180695"}], "href": "https://doi.org/10.1242/dev.180695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31932351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31932351"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qing Yue, Kuan Li, Zhaoyu Song, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitric oxide hinders club cell proliferation through Gdpd2 during allergic airway inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Open Bio (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/2211-5463.13617"}], "href": "https://doi.org/10.1002/2211-5463.13617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37078963"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37078963"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shijie Sun, Ning Wang, Ziwen Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-5692a promotes proliferation and inhibits apoptosis by targeting HOXD8 in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J BUON (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30941968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30941968"}]}]}]}