{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nXAF1 is rapidly induced by interferons and other stress‐related signals, acting as an immediate early gene that enhances cellular sensitivity to apoptotic triggers. In interferon‐responsive cells, IFN‑α/β and IFN‑γ stimulation promote robust XAF1 messenger RNA and protein expression that in turn sensitizes cells to death ligands such as TRAIL via STAT‐mediated pathways. This interferon‐dependent induction of XAF1 thereby functions as a key component of the stress response—amplifying apoptosis in vascular and immune cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, XAF1 functions as a potent tumor‐suppressor by directly antagonizing inhibitors of apoptosis. It binds to XIAP and several other IAP family proteins, thereby relieving caspase inhibition and facilitating the ubiquitination and degradation of anti‐apoptotic mediators such as Survivin. In addition, XAF1 engages in positive feedback loops with transcriptional regulators—including p53 and interferon regulatory factor‑1—and its specific zinc‐finger domains are critical for these protein–protein interactions. Such mechanistic insights also extend to stress conditions (for example, heavy metal exposure) where XAF1 promotes degradation of survival factors, underscoring its central role in modulating apoptotic signaling cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA wealth of clinical and epigenetic studies has now established that XAF1 expression is frequently attenuated in a broad spectrum of human malignancies due to promoter hypermethylation, aberrant transcriptional repression and alternative splicing. In cancers of the gastrointestinal tract, urogenital system, and central nervous system—and even in inflammatory conditions like sarcoidosis—loss or alteration of XAF1 is strongly associated with advanced tumor stage, resistance to chemotherapy or radiotherapy, and poorer patient survival. Notably, re‐establishing XAF1 expression either through demethylation strategies or gene therapy restores apoptotic sensitivity and curbs tumor growth, underscoring its promise as both a prognostic biomarker and a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Douglas W Leaman, Mamta Chawla-Sarkar, Keyur Vyas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M204851200"}], "href": "https://doi.org/10.1074/jbc.M204851200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12029096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12029096"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "F Gilli, F Marnetto, M Caldano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mult Scler (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1191/135248506ms1245oa"}], "href": "https://doi.org/10.1191/135248506ms1245oa"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16459719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16459719"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Frederic J Reu, Soo In Bae, Leonid Cherkassky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overcoming resistance to interferon-induced apoptosis of renal carcinoma and melanoma cells by DNA demethylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2005.03.4074"}], "href": "https://doi.org/10.1200/JCO.2005.03.4074"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16801630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16801630"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yunwei Sun, Liang Qiao, Harry Hua-Xiang Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2007.10.014"}], "href": "https://doi.org/10.1016/j.canlet.2007.10.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18035482"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18035482"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yalai Bai, Usman Ahmad, Yinong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interferon-gamma induces X-linked inhibitor of apoptosis-associated factor-1 and Noxa expression and potentiates human vascular smooth muscle cell apoptosis by STAT3 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M706021200"}], "href": "https://doi.org/10.1074/jbc.M706021200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18192275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18192275"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Do-Sun Byun, Kyucheol Cho, Byung-Kyu Ryu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2003)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14612497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14612497"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Vinay Arora, Herman H Cheung, Stéphanie Plenchette, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M700776200"}], "href": "https://doi.org/10.1074/jbc.M700776200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17613533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17613533"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jide Wang, Qing Gu, Ming Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of XAF1 as a novel cell cycle regulator through modulating G(2)/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgp155"}], "href": "https://doi.org/10.1093/carcin/bgp155"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19628579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19628579"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Wenjing Zhang, Zheng Guo, Bo Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a functional p53 responsive element within the promoter of XAF1 gene in gastrointestinal cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo_00000584"}], "href": "https://doi.org/10.3892/ijo_00000584"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20198350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20198350"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Man Kit Tse, Chi Kong Cho, Wai Fung Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Domain organization of XAF1 and the identification and characterization of XIAP(RING) -binding domain of XAF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pro.2126"}], "href": "https://doi.org/10.1002/pro.2126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22811387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22811387"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Ga Bin Park, Yeong-Seok Kim, Daejin Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melphalan-induced apoptosis of EBV-transformed B cells through upregulation of TAp73 and XAF1 and nuclear import of XPA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1203442"}], "href": "https://doi.org/10.4049/jimmunol.1203442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24249729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24249729"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Min-Goo Lee, Jikhyon Han, Seong-In Jeong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 directs apoptotic switch of p53 signaling through activation of HIPK2 and ZNF313."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1411746111"}], "href": "https://doi.org/10.1073/pnas.1411746111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25313037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25313037"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Cheol-Hee Shin, Min-Goo Lee, Jikhyon Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of XAF1-MT2A mutual antagonism as a molecular switch in cell-fate decisions under stressful conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1700861114"}], "href": "https://doi.org/10.1073/pnas.1700861114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28507149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28507149"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Seong-In Jeong, Jung-Wook Kim, Kyung-Phil Ko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 forms a positive feedback loop with IRF-1 to drive apoptotic stress response and suppress tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-018-0867-4"}], "href": "https://doi.org/10.1038/s41419-018-0867-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30042418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30042418"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "B Camacho-Moctezuma, M Quevedo-Castillo, J Melendez-Zajgla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YY1 negatively regulates the XAF1 gene expression in prostate cancer."}]}, {"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.2018.12.056"}], "href": "https://doi.org/10.1016/j.bbrc.2018.12.056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30551877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30551877"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Kin Cheung P Ng, Eric I Campos, Magdalena Martinka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 expression is significantly reduced in human melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.0022-202X.2004.23467.x"}], "href": "https://doi.org/10.1111/j.0022-202X.2004.23467.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15610524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15610524"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Jide Wang, Hua He, Lifen Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSF1 down-regulates XAF1 through transcriptional regulation."}]}, {"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.M505890200"}], "href": "https://doi.org/10.1074/jbc.M505890200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16303760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16303760"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Weihong Yin, Satish Cheepala, John L Clifford "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel splice variant of X-linked inhibitor of apoptosis-associated factor 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.11.128"}], "href": "https://doi.org/10.1016/j.bbrc.2005.11.128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16343440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16343440"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Xiaolei Fang, Zhaoxu Liu, Yidong Fan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Switch to full-length of XAF1 mRNA expression in prostate cancer cells by the DNA methylation inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.21636"}], "href": "https://doi.org/10.1002/ijc.21636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16353137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16353137"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "M-G Lee, J-S Huh, S-K Chung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209867"}], "href": "https://doi.org/10.1038/sj.onc.1209867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16909101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16909101"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Bing Zou, Chor Sang Chim, Hui Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correlation between the single-site CpG methylation and expression silencing of the XAF1 gene in human gastric and colon cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2006.09.050"}], "href": "https://doi.org/10.1053/j.gastro.2006.09.050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17087954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17087954"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "O Cristina Micali, Herman H Cheung, Stéphanie Plenchette, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of the XAF1 gene by promoter hypermethylation in cancer cells and reactivation to TRAIL-sensitization by IFN-beta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-7-52"}], "href": "https://doi.org/10.1186/1471-2407-7-52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17376236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17376236"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Carsten Kempkensteffen, Stefan Hinz, Mark Schrader, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2007.03.006"}], "href": "https://doi.org/10.1016/j.canlet.2007.03.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17449173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17449173"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Sun-Ku Chung, Min-Goo Lee, Byung-Kyu Ryu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2007.04.024"}], "href": "https://doi.org/10.1053/j.gastro.2007.04.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17570219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17570219"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Marcos B Pinho, Fernanda Costas, João Sellos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 mRNA expression improves progression-free and overall survival for patients with advanced bladder cancer treated with neoadjuvant chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Urol Oncol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.urolonc.2008.03.016"}], "href": "https://doi.org/10.1016/j.urolonc.2008.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18555708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18555708"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Feng Zhang, Li-Ming Wu, Lin Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Predictive value of expression and promoter hypermethylation of XAF1 in hepatitis B virus-associated hepatocellular carcinoma treated with transplantation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Surg Oncol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1245/s10434-008-0146-1"}], "href": "https://doi.org/10.1245/s10434-008-0146-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18830757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18830757"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jide Wang, Wenjing Zhang, Yusheng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "c-Jun N-terminal kinase (JNK1) upregulates XIAP-associated factor 1 (XAF1) through interferon regulatory factor 1 (IRF-1) in gastrointestinal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgn271"}], "href": "https://doi.org/10.1093/carcin/bgn271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19056926"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19056926"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Shui Ping Tu, Peter Liston, Jian Tao Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Restoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.24282"}], "href": "https://doi.org/10.1002/ijc.24282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19358264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19358264"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Claudia Augello, Luca Caruso, Marco Maggioni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-9-125"}], "href": "https://doi.org/10.1186/1471-2407-9-125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19397802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19397802"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jia Huang, Wei-yan Yao, Qi Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 as a prognostic biomarker and therapeutic target in pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1349-7006.2009.01396.x"}], "href": "https://doi.org/10.1111/j.1349-7006.2009.01396.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19922503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19922503"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Bing Zou, Chor S Chim, Roberta Pang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.20807"}], "href": "https://doi.org/10.1002/mc.20807"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21678496"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21678496"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Xiang-Yu Chen, Qiao-Yu He, Ming-Zhou Guo "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 is frequently methylated in human esophageal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v18.i22.2844"}], "href": "https://doi.org/10.3748/wjg.v18.i22.2844"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22719195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22719195"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "YunXia Wang, HongLuan Mao, QingZhi Hao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of expression of XIAP-associated factor 1 (XAF1) with clinicopathologic factors, overall survival, microvessel density and cisplatin-resistance in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Regul Pept (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.regpep.2012.06.005"}], "href": "https://doi.org/10.1016/j.regpep.2012.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22759793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22759793"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Xigui Long, Ying Li, Yiming Qi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XAF1 contributes to dengue virus-induced apoptosis in vascular endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.12-213967"}], "href": "https://doi.org/10.1096/fj.12-213967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23207547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23207547"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Zhi-Qiang Ling, Ping Lv, Xiao-Xiao Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating Methylated XAF1 DNA Indicates Poor Prognosis for Gastric Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0067195"}], "href": "https://doi.org/10.1371/journal.pone.0067195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23826230"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23826230"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Albert M Levin, Michael C Iannuzzi, Courtney G Montgomery, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Admixture fine-mapping in African Americans implicates XAF1 as a possible sarcoidosis risk gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0092646"}], "href": "https://doi.org/10.1371/journal.pone.0092646"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24663488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24663488"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Wen-Jing Zhao, Bo-Ya Deng, Xue-Mei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XIAP associated factor 1 (XAF1) represses expression of X-linked inhibitor of apoptosis protein (XIAP) and regulates invasion, cell cycle, apoptosis, and cisplatin sensitivity of ovarian carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian Pac J Cancer Prev (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7314/apjcp.2015.16.6.2453"}], "href": "https://doi.org/10.7314/apjcp.2015.16.6.2453"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25824780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25824780"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Minzhu Ren, Zhenhua Wang, Guowei Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impact of X-linked inhibitor of apoptosis protein on survival of nasopharyngeal carcinoma patients following radiotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-016-5029-7"}], "href": "https://doi.org/10.1007/s13277-016-5029-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27048285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27048285"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Ga Bin Park, Sang Hyun Park, Daejin Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Berberine induces mitochondrial apoptosis of EBV-transformed B cells through p53-mediated regulation of XAF1 and GADD45α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2016.3502"}], "href": "https://doi.org/10.3892/ijo.2016.3502"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27121748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27121748"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Chaoqun Wang, Lijuan Li, Zhixia Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An indel polymorphism within pre-miR3131 confers risk for hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgw206"}], "href": "https://doi.org/10.1093/carcin/bgw206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28034876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28034876"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Jung Rock Moon, Shin Ju Oh, Chang Kyun Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGF-β1 protects colon tumor cells from apoptosis through XAF1 suppression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2019.4776"}], "href": "https://doi.org/10.3892/ijo.2019.4776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31081052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31081052"}]}]}]}