{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KIAA1210 is emerging as a multifunctional protein with context‐dependent roles in both tumor biology and spermatogenesis. In prostate cancer tissues, its significant downregulation suggests that it may have tumor‐suppressive properties, although its precise mechanistic role in tumor progression remains to be fully defined."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the testis, KIAA1210 is expressed predominantly and localizes to key structures—including the sex body, acrosome, and regions adjacent to cell junctions—implying an important role in cell junction organization. Detailed proteomic analyses have revealed that KIAA1210 contains protein domains (including a TOP2‐associated PAT1 domain, an HSV-1 UL36 hypothetical domain, and a provisional DNA translocase FtsK domain) and forms complexes with topoisomerase II isoforms, particularly TOP2B. This interaction suggests that KIAA1210 may regulate dynamic chromatin changes and be essential for the proper assembly or function of ectoplasmic specializations during spermiogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and has been further implicated as an intercellular bridge component involved in germ cell communication and possibly epigenetic regulation during meiosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, genetic investigations in male infertility have identified deleterious variants of KIAA1210 in patients exhibiting sperm head abnormalities and defective acrosomal biogenesis, implicating loss-of-function of this gene in abnormal sperm development that may adversely affect assisted reproductive outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Beyond its roles in reproductive biology, differential methylation of regulatory regions of KIAA1210 in peripheral blood is emerging as a potential biomarker. Specifically, hypermethylation at the KIAA1210 locus in white blood cells has been associated with an increased risk of hepatocellular carcinoma in cirrhotic patients, further underscoring the gene’s involvement in disease pathogenesis and its promise in clinical diagnostics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight KIAA1210 as a versatile protein that participates in the regulation of chromatin dynamics and cell junction integrity during spermatogenesis, while its altered expression and methylation patterns in pathological conditions such as prostate cancer and hepatocellular carcinoma suggest it may serve as both a functional player in normal cellular processes and a valuable biomarker for disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Donkena Krishna Vanaja, Karla V Ballman, Bruce W Morlan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDLIM4 repression by hypermethylation as a potential biomarker for prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-05-2072"}], "href": "https://doi.org/10.1158/1078-0432.CCR-05-2072"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16489065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16489065"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tokuko Iwamori, Naoki Iwamori, Masaki Matsumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of KIAA1210 as a novel X-chromosome-linked protein that localizes to the acrosome and associates with the ectoplasmic specialization in testes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.116.145458"}], "href": "https://doi.org/10.1095/biolreprod.116.145458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28203736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28203736"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tokuko Iwamori, Naoki Iwamori, Masaki Matsumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel localizations and interactions of intercellular bridge proteins revealed by proteomic profiling†."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/biolre/ioaa017"}], "href": "https://doi.org/10.1093/biolre/ioaa017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31995159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31995159"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yaqian Li, Yan Wang, Yuting Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/deab229"}], "href": "https://doi.org/10.1093/humrep/deab229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34791246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34791246"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Katarzyna Lubecka, Kirsty Flower, Megan Beetch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15592294.2018.1481706"}], "href": "https://doi.org/10.1080/15592294.2018.1481706"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29927686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29927686"}]}]}]}