{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCRIPTO-3 is a processed pseudogene of CRIPTO-1 located on the X chromosome that is expressed in undifferentiated embryonal carcinoma cells. In these cells, CRIPTO-3 is regulated in parallel with CRIPTO-1, as both are subject to transcriptional repression by the orphan nuclear receptor GCNF during retinoic acid-induced differentiation. This regulatory mechanism suggests that CRIPTO-3, like CRIPTO-1, is part of an important stem cell “stemness” network that is normally down-regulated upon differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer settings, CRIPTO-3 assumes oncogenic functions. Studies have demonstrated that CRIPTO-3 mRNA is the predominant CRIPTO message expressed in many tumor samples, and that the CRIPTO-3 protein, differing from CRIPTO-1 by only a few amino acids, actively participates in the Nodal-dependent signaling pathway. This functional equivalence in signaling supports its role in promoting tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in colorectal cancer, the teratocarcinoma-derived growth factor 1 pseudogene 3 (TDGF1P3), essentially synonymous with CRIPTO-3, is markedly upregulated. This pseudogene promotes oncogenesis by binding to miR-338-3p, thereby preventing the miRNA from targeting pyruvate kinase M2 (PKM2). The resultant derepression of PKM2 contributes to enhanced proliferation, migration, and invasion of cancer cells, highlighting a novel mechanism by which CRIPTO-3/TDGF1P3 may drive tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Moritz Hentschke, Ingo Kurth, Uwe Borgmeyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germ cell nuclear factor is a repressor of CRIPTO-1 and CRIPTO-3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M606975200"}], "href": "https://doi.org/10.1074/jbc.M606975200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16954206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16954206"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chao Sun, Olivia Orozco, Dian L Olson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRIPTO3, a presumed pseudogene, is expressed in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.09.113"}], "href": "https://doi.org/10.1016/j.bbrc.2008.09.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18835250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18835250"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qianwen Ni, Min An, Shi Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pseudogene TDGF1P3 regulates the proliferation and metastasis of colorectal cancer cells via the miR-338-3p-PKM2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2022.11.054"}], "href": "https://doi.org/10.1016/j.bbrc.2022.11.054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36436343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36436343"}]}]}]}