{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPARPBP, also known as PARI or C12orf48, is emerging as a critical regulator of DNA repair and replication stress responses. It directly interacts with PARP‐1 and PCNA to modulate poly(ADP‐ribosyl)ation and to restrict unscheduled homologous recombination (HR) events by limiting DNA repair synthesis. These activities help maintain genomic stability by preventing aberrant recombination at stalled replication forks and promoting appropriate nascent strand processing under both endogenous and exogenous replication stress conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancer types, including pancreatic, gastric, cervical, lung, and myeloid leukemia, PARPBP is frequently overexpressed and functions as an oncogenic factor. In pancreatic ductal adenocarcinoma, its enhanced expression increases DNA damage tolerance, promotes cell-cycle alterations, and supports tumor growth by positively regulating PARP‐1 activity. In gastric cancer, PARPBP expression is transcriptionally driven by the oncogene FOXM1, contributing to increased cell proliferation, migration, and metastatic potential. Similarly, in myeloid leukemia its overexpression suppresses differentiation through modulation of key signaling pathways such as NF-κB, while preliminary studies in lung adenocarcinoma further suggest its role in tumor progression. These findings collectively emphasize its potential as a therapeutic target in aggressive and therapy‐resistant malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional regulatory layers further diversify PARPBP function. For instance, aberrant alternative splicing events—modulated by noncoding RNAs such as SNORA70E—can produce distinct transcript isoforms (e.g., PARPBP-15) that enhance cell invasion, migration, and proliferation, thereby contributing to tumor aggressiveness in ovarian cancer. This exemplifies the multifaceted regulation of PARPBP in cancer biology and underscores its promise as both a diagnostic marker and a candidate target for novel therapeutic strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lianhua Piao, Hidewaki Nakagawa, Koji Ueda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C12orf48, termed PARP-1 binding protein, enhances poly(ADP-ribose) polymerase-1 (PARP-1) activity and protects pancreatic cancer cells from DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20828"}], "href": "https://doi.org/10.1002/gcc.20828"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20931645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20931645"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "George-Lucian Moldovan, Donniphat Dejsuphong, Mark I R Petalcorin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of homologous recombination by the PCNA-interacting protein PARI."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2011.11.010"}], "href": "https://doi.org/10.1016/j.molcel.2011.11.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22153967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22153967"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peter Burkovics, Lili Dome, Szilvia Juhasz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkw024"}], "href": "https://doi.org/10.1093/nar/gkw024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26792895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26792895"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ayako L Mochizuki, Ami Katanaya, Eri Hayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PARI Regulates Stalled Replication Fork Processing To Maintain Genome Stability upon Replication Stress in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00117-17"}], "href": "https://doi.org/10.1128/MCB.00117-17"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28894029"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28894029"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kevin W O'Connor, Donniphat Dejsuphong, Eunmi Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PARI overexpression promotes genomic instability and pancreatic tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-3313"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-3313"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23436799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23436799"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bin Yu, Youming Ding, Xiaofeng Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of PARPBP Correlates with Tumor Progression and Poor Prognosis in Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dig Dis Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10620-019-05608-4"}], "href": "https://doi.org/10.1007/s10620-019-05608-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30949905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30949905"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yi Zhang, Xiaojuan Ye, Lizhi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PARI functions as a new transcriptional target of FOXM1 involved in gastric cancer development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.23945"}], "href": "https://doi.org/10.7150/ijbs.23945"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29805304"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29805304"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Claudia M Nicolae, Michael J O'Connor, Emily M Schleicher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PARI (PARPBP) suppresses replication stress-induced myeloid differentiation in leukemia cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-0810-x"}], "href": "https://doi.org/10.1038/s41388-019-0810-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30967629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30967629"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Dong Xu, Zheng Tao, Xing Tang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Poly (ADP-ribose) polymerase-1 Binding Protein Facilitates Lung Adenocarcinoma Cell Proliferation and Correlates with Poor Prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Clin Lab Sci (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31611199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31611199"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shuo Chen, Qian-Hui Li, Xi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNORA70E promotes the occurrence and development of ovarian cancer through pseudouridylation modification of RAP1B and alternative splicing of PARPBP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.17540"}], "href": "https://doi.org/10.1111/jcmm.17540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36056690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36056690"}]}]}]}