{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent investigations in pancreatic cancer have revealed that genetic variation can impact chromatin organization and gene regulation in ways that influence tumorigenesis. In one study, a common single nucleotide polymorphism (rs2001389) was shown to weaken the binding of the CCCTC-binding factor (CTCF) at the boundaries of topologically associating domains (TADs), which in turn led to reduced expression of MFSD13A. Functional experiments demonstrated that when MFSD13A—proposed to act as an antioncogene—is underexpressed, pancreatic cancer cells proliferate more readily. These findings suggest that MFSD13A plays a tumor-suppressive role by modulating cell growth, implicating its reduced expression as a contributing factor in pancreatic cancer development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a related effort aimed at identifying novel therapeutic targets, research on colorectal cancer focused on a different membrane protein, TMEM180. Although functionally distinct from MFSD13A, TMEM180 was characterized as a multi-pass membrane protein possessing 12 transmembrane domains and conserved cation-binding sites, features reminiscent of known cation symporters. This structural insight supports the hypothesis that TMEM180 facilitates cation transport, a function that may be relevant for both the metabolism and pathology of colorectal cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther extending the biological significance of TMEM180, integrative analyses in schizophrenia have linked reduced TMEM180 mRNA expression with an increased risk of the disorder. Down-regulation of TMEM180 was observed in both the peripheral blood of patients and in postmortem brain samples, and experimental knockdown in neural stem cells disrupted normal proliferation and differentiation. These results underscore TMEM180’s potential involvement in neurodevelopment and synaptic regulation, highlighting its relevance beyond oncology into neuropsychiatric disease research."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shufang Mei, Juntao Ke, Jianbo Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A functional variant in the boundary of a topological association domain is associated with pancreatic cancer risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.23077"}], "href": "https://doi.org/10.1002/mc.23077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31237042"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31237042"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takahiro Anzai, Yasuhiro Matsumura "}, {"type": "b", "children": [{"type": "t", "text": "Topological analysis of TMEM180, a newly identified membrane protein that is highly expressed in colorectal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.10.070"}], "href": "https://doi.org/10.1016/j.bbrc.2019.10.070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31615651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31615651"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun-Yang Wang, Xiao-Yan Li, Hui-Juan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrative Analyses Followed by Functional Characterization Reveal TMEM180 as a Schizophrenia Risk Gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Schizophr Bull (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/schbul/sbab032"}], "href": "https://doi.org/10.1093/schbul/sbab032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33768244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33768244"}]}]}]}