{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The human chorionic gonadotropin (hCG) β‐subunit gene cluster encodes several related genes that are essential for successful implantation and maintenance of pregnancy. Although CGB1 was long considered a pseudogene, accumulating evidence indicates that it is actively transcribed and likely encodes a novel protein. Comparative analyses in primates have demonstrated that CGB1 (together with CGB2) originated relatively recently and is highly conserved between humans and African great apes, suggesting that its protein product fulfills an as‐yet–uncharacterized function distinct from classical hCGβ (such as that encoded by CGB3, CGB5, CGB7, and CGB8)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In trophoblastic tissues, robust expression of CGB1 has been detected early in pregnancy and is strongly associated with implantation and placental development; furthermore, deviations in its expression patterns have been linked to adverse pregnancy outcomes. For instance, normal and ectopic pregnancies display an expression peak of CGB1 during the first trimester, a switch that is absent in recurrent miscarriage cases, implying that proper CGB1 activation is important for implantation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in reproduction, emerging data highlight a potential involvement of CGB1 in tumor biology. Transcripts from CGB1 (and CGB2) have been detected in several tissues normally not associated with placental function, including testicular and pituitary tissues, and in various epithelial cancers. In cancer cell models, silencing of CGB1/2 results in a reduction in secreted hCGβ and a concomitant decrease in cell survival, suggesting that these genes may confer a growth‐promoting or anti‐apoptotic advantage in tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CGB1 appears to be an evolutionarily young and functionally active component of the hCGβ gene cluster. Its expression is tightly regulated—likely influenced by promoter methylation and associated transcription factor networks—and is critical for proper implantation and early placental development. Moreover, aberrant activation of CGB1 may contribute to tumorigenesis by promoting hCGβ secretion and enhancing cell survival. These multifaceted roles underscore the need for further functional studies to fully elucidate the contribution of CGB1 to both reproductive and oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pille Hallast, Kristiina Rull, Maris Laan "}, {"type": "b", "children": [{"type": "t", "text": "The evolution and genomic landscape of CGB1 and CGB2 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2005.11.049"}], "href": "https://doi.org/10.1016/j.mce.2005.11.049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17055150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17055150"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kristiina Rull, Maris Laan "}, {"type": "b", "children": [{"type": "t", "text": "Expression of beta-subunit of HCG genes during normal and failed pregnancy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dei261"}], "href": "https://doi.org/10.1093/humrep/dei261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16123088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16123088"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Aleksandra Głodek, Marta J Kubiczak, Grzegorz P Walkowiak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation status of human chorionic gonadotropin beta subunit promoter and TFAP2A expression as factors regulating CGB gene expression in placenta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Fertil Steril (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.fertnstert.2014.06.016"}], "href": "https://doi.org/10.1016/j.fertnstert.2014.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25063728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25063728"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Beata B Burczynska, Latifa Kobrouly, Stephen A Butler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel insights into the expression of CGB1 & 2 genes by epithelial cancer cell lines secreting ectopic free hCGβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Res (2014)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24778026"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24778026"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marta Kubiczak, Grzegorz P Walkowiak, Ewa Nowak-Markwitz, et al. 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