{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies highlight that PRXL2A and its homologs play pivotal roles in cancer by acting as redox regulators that protect cells from oxidative stress. In oral squamous cell carcinoma, downregulation of miR-125b leads to an upregulation of PRXL2A, which in turn activates NRF2 and confers resistance to oxidative damage and chemotherapeutic agents, thereby contributing to tumor progression and poorer patient outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In acute myeloid leukemia, elevated expression of FAM213A (a synonym of PRXL2A) is associated with adverse prognosis; mechanistic studies in zebrafish further demonstrate that it supports myelopoiesis and negatively regulates the p53 tumor suppressor pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn non-malignant settings, PRXL2A-related proteins such as PAMM are crucial for maintaining cellular redox homeostasis. In bone marrow monocytes, wild-type PAMM—with an intact CXXC motif—enhances the reduced state of the cell (as evidenced by an increased GSH/GSSG ratio) and mitigates hydrogen peroxide-induced stress, thereby inhibiting osteoclast differentiation through suppression of NF-κB and c-Jun signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, in bone tissue exposed to oxidative stress—for instance, in estrogen-deficient conditions—upregulation of PAMM is mediated by Akt phosphorylation, suggesting that this protein may contribute to estrogen-driven protection against oxidative damage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, PRXL2A homologs exhibit anti‐inflammatory properties beyond their intracellular antioxidant function. PAMM, which is secreted by mature adipocytes, has been shown to attenuate lipopolysaccharide-induced inflammatory responses in macrophages by suppressing MAPK signaling pathways. This secreted factor thus emerges as an important modulator of macrophage activation and may help mitigate obesity-related inflammatory complications."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yi-Fen Chen, Yun-Yen Wei, Cheng-Chieh Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2019.101140"}], "href": "https://doi.org/10.1016/j.redox.2019.101140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30785086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30785086"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chang-Kyu Oh, Mihyang Ha, Myoung-Eun Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM213A is linked to prognostic significance in acute myeloid leukemia through regulation of oxidative stress and myelopoiesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hematol Oncol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hon.2728"}], "href": "https://doi.org/10.1002/hon.2728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32124993"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32124993"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yan Xu, Leslie R Morse, Raquel Assed Bezerra da Silva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAMM: a redox regulatory protein that modulates osteoclast differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2009.2886"}], "href": "https://doi.org/10.1089/ars.2009.2886"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19951071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19951071"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yan Xu, Leslie R Morse, Raquel Assed Bezerra da Silva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A short report: PAMM, a novel antioxidant protein, induced by oxidative stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Redox Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.redox.2015.09.008"}], "href": "https://doi.org/10.1016/j.redox.2015.09.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26402163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26402163"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Fang Guo, Hui He, Zhi-Chao Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting MAPK signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20150019"}], "href": "https://doi.org/10.1042/BJ20150019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26438880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26438880"}]}]}]}