{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nIn thyroid cancer, METTL7A exhibits an intriguing epigenetic regulation mechanism. A study showed that a reduction in gene‐body (intragenic) methylation of METTL7A in thyroid cancer cells, compared to normal thyroid cells, alters its transcription. Mutation of a specific CpG site within the gene body resulted in enhanced RNA polymerase II recruitment and diminished binding of methyl-CpG binding protein-2; additionally, EZH2, a subunit of the polycomb repressor complex 2, may guide this methylation process."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the human cerebellum, METTL7A is predominantly localized in GFAP-positive cells, particularly within the end-feet of Bergmann glia at the cerebrospinal fluid-brain parenchyma barrier. Its presence at the contacts between Bergmann glia and Purkinje neurons, as well as in lipid droplets in white matter, suggests a potential role in maintaining cerebellar homeostasis and modulating synaptic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn malignancies such as melanoma, downregulation of METTL7A correlates with a more aggressive tumor phenotype, including increased proliferation, invasion, migration, and colony formation. Mechanistic investigations have linked this tumorigenic behavior to inhibition of the p53 signaling pathway, and low METTL7A expression is further associated with reduced immune cell infiltration and less favorable responses to chemotherapy and immunotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, METTL7A, together with its paralog METTL7B, plays an important role in drug resistance. Specifically, these methyltransferases can methylate the thiol group present in thiol-based histone deacetylase inhibitors (HDACis), such as romidepsin. This methylation inactivates the zinc-binding moiety of the drugs, thereby conferring a selective resistance to these HDACis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shasha Zhou, Yihang Shen, Min Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation of METTL7A gene body regulates its transcriptional level in thyroid cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.16147"}], "href": "https://doi.org/10.18632/oncotarget.16147"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28416772"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28416772"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "América Vera-Montecinos, Jordi Galiano-Landeira, Mònica Roldán, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Localization of METTL7A in Bergmann Glial Cells in Human Cerebellum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms24098405"}], "href": "https://doi.org/10.3390/ijms24098405"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37176112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37176112"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Duoli Zhang, Tao Zou, Qingsong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptomic characterization revealed that METTL7A inhibits melanoma progression via the p53 signaling pathway and immunomodulatory pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PeerJ (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7717/peerj.15799"}], "href": "https://doi.org/10.7717/peerj.15799"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37547717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37547717"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Robert W Robey, Christina M Fitzsimmons, Wilfried M Guiblet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-23-0144"}], "href": "https://doi.org/10.1158/1535-7163.MCT-23-0144"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38151817"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38151817"}]}]}]}