{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe studies provided describe a multifaceted role for the E3 ubiquitin ligase FBXO22 in diverse cellular contexts. In one investigation, FBXO22 forms a complex with KDM4A to target methylated p53 for ubiquitin‐mediated degradation, a process crucial for inducing cellular senescence and the associated secretory phenotype. This work also showed that loss of Fbxo22 in mice leads to p53 accumulation and growth retardation, underscoring its importance in regulating p53‐dependent senescence processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAnother study demonstrated that FBXO22 promotes Lys‐63–linked polyubiquitination of LKB1, thereby inhibiting its kinase activity. This modification disrupts the LKB1–AMPK–mTOR signaling cascade, resulting in enhanced non–small cell lung cancer cell growth and linking high FBXO22 expression with poor prognosis in lung adenocarcinoma patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA further investigation in prostate cancer revealed that elevated FBXO22 expression promotes bone metastasis by two mechanisms. First, FBXO22 in macrophages facilitates a switch to an M2‐polarized state, which supports tumor progression. Second, it degrades the transcription factor KLF4, leading to increased transcription of nerve growth factor (NGF) and activation of the NGF/tropomyosin receptor kinase A pathway, thereby promoting cancer cell activity and osteogenic lesions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIt is important to note that none of these abstracts provide data on MIR6892; rather, they collectively highlight the diverse molecular functions of FBXO22. Without additional evidence or direct mention, any function attributed to MIR6892 remains undefined in the context of these reports.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yoshikazu Johmura, Jia Sun, Kyoko Kitagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10574"}], "href": "https://doi.org/10.1038/ncomms10574"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26868148"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26868148"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiao-Na Zhu, Ping He, Liang Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FBXO22 mediates polyubiquitination and inactivation of LKB1 to promote lung cancer cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-019-1732-9"}], "href": "https://doi.org/10.1038/s41419-019-1732-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31217475"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31217475"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuehua Zhang, Wen Li, Shenghu Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FBXO22 Mediates the NGF/TRKA Signaling Pathway in Bone Metastases in Prostate Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2023.05.012"}], "href": "https://doi.org/10.1016/j.ajpath.2023.05.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37301536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37301536"}]}]}]}