{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:59:09Z","timestamp":1788479949391,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T00:00:00Z","timestamp":1612051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Minister of Science and Higher Education","award":["SUB.B130.20.022 (record numbers in the Simple system)"],"award-info":[{"award-number":["SUB.B130.20.022 (record numbers in the Simple system)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>(1) Background: Poly(ADP-ribose) polymerase 1) (PARP1) is a pleiotropic enzyme involved in several cellular processes, e.g., DNA damage repair, regulation of mitosis, and immune response. Little is known about the role of PARP1 in melanoma development and progression. We aimed to investigate the prognostic significance of PARP1 expression in cutaneous melanoma through evaluation of mRNA and protein levels of PARP1 in normal melanocytes and melanoma cell lines, as well as in patients\u2019 tissue material from surgical resections. (2) Methods: An in vitro model was based on two types of normal human melanocytes (HEMn-DP and HEMn-LP) and four melanoma cell lines (A375, WM1341D, Hs294T, and WM9). PARP1 mRNA gene expression was estimated using real-time polymerase chain reaction (RT-PCR), whereas the protein level of PARP1 was evaluated by fluorescence confocal microscopy and then confirmed by Western Blotting analysis. The expression of PARP1 was also assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissues of 128 primary cutaneous melanoma patients and correlated with follow-up and clinicopathologic features. (3) Results: The in vitro study showed that melanoma cells exhibited significantly higher PARP1 expression at mRNA and protein levels than normal melanocytes. High PARP1 expression was also associated with the invasiveness of tumor cells. Elevated nuclear PARP1 expression in patients without nodal metastases strongly correlated with significantly shorter disease-free survival (p = 0.0015) and revealed a trend with shorter cancer-specific overall survival (p = 0.05). High PARP1 immunoreactivity in the lymph node-negative group of patients was significantly associated with higher Breslow tumor thickness, presence of ulceration, and a higher mitotic index (p = 0.0016, p = 0.023, and p &lt; 0.001, respectively). In patients with nodal metastases, high PARP1 expression significantly correlated with the presence of microsatellitosis (p = 0.034), but we did not confirm the prognostic significance of PARP1 expression in these patients. In the entire analyzed group of patients (with and without nodal metastases at the time of diagnosis), PARP1 expression was associated with a high mitotic index (p = 0.001) and the presence of ulceration (p = 0.036). Moreover, in patients with elevated PARP1 expression, melanoma was more frequently located in the skin of the head and neck region (p = 0.015). In multivariate analysis, high PARP1 expression was an independent unfavorable prognosticator in lymph node-negative cutaneous melanoma patients. (4) Conclusions: In vitro molecular biology approaches demonstrated enhanced PARP1 expression in cutaneous melanoma. These results were confirmed by the immunohistochemical study with clinical parameter analysis, which showed that a high level of PARP1 correlated with unfavorable clinical outcome. These observations raise the potential role of PARP1 inhibitor-based therapy in cutaneous melanoma.<\/jats:p>","DOI":"10.3390\/cells10020286","type":"journal-article","created":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T21:31:56Z","timestamp":1612128716000},"page":"286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["PARP1 as a Marker of an Aggressive Clinical Phenotype in Cutaneous Melanoma\u2014A Clinical and an In Vitro Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-7050","authenticated-orcid":false,"given":"Piotr","family":"Kupczyk","sequence":"first","affiliation":[{"name":"Department of Pathomorphology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Simiczyjew","sequence":"additional","affiliation":[{"name":"Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Marczuk","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Research and Development Center, Regional Specialized Hospital, 51-124 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-3513","authenticated-orcid":false,"given":"Ewelina","family":"Dratkiewicz","sequence":"additional","affiliation":[{"name":"Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-3004","authenticated-orcid":false,"given":"Artur","family":"Beberok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-4339","authenticated-orcid":false,"given":"Jakub","family":"Rok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Pieniazek","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Tadeusz Koszarowski Regional Oncology Centre, 45-061 Opole, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-1823","authenticated-orcid":false,"given":"Przemyslaw","family":"Biecek","sequence":"additional","affiliation":[{"name":"Faculty of Mathemathics and Information Science, Warsaw University of Technology, 00-662 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Nevozhay","sequence":"additional","affiliation":[{"name":"Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"School of Biomedicine, Far Eastern Federal University, 690950 Vladivostok, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Slowikowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Chodaczek","sequence":"additional","affiliation":[{"name":"Laboratory of Bioimaging, \u0141ukasiewicz Research Network\u2014PORT Polish Center for Technology Development, 54-066 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6918-3330","authenticated-orcid":false,"given":"Dorota","family":"Wrzesniok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Cell Pathology, Faculty of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8729-6216","authenticated-orcid":false,"given":"Piotr","family":"Donizy","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,31]]},"reference":[{"key":"ref_1","unstructured":"Matthews, N.H., Li, W.-Q., Qureshi, A.A., Weinstock, M.A., and Cho, E. (2017). Epidemiology of Melanoma. Cutaneous Melanoma: Etiology and Therapy, Wb Saunders."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.5114\/wo.2018.73889","article-title":"Immunotherapy of melanoma","volume":"2018","author":"Lugowska","year":"2018","journal-title":"Wsp\u00f3\u0142czesna Onkol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Moreira, A., Heinzerling, L., and Bhardwaj, N. (2021). Current melanoma treatments: Where do we stand?. Cancers, 13.","DOI":"10.3390\/cancers13020221"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Simiczyjew, A., Dratkiewicz, E., Mazurkiewicz, J., Zi\u0119tek, M., Matkowski, R., and Nowak, D. (2020). The influence of tumor microenvironment on immune escape of melanoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218359"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s13555-019-0292-3","article-title":"Beyond PD-1 Immunotherapy in malignant melanoma","volume":"9","author":"Kwiatkowska","year":"2019","journal-title":"Dermatol. Ther."},{"key":"ref_6","first-page":"265","article-title":"PARP Inhibitors: The cornerstone of DNA repair-targeted therapies","volume":"31","author":"Kohn","year":"2017","journal-title":"Oncology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2147\/ITT.S134842","article-title":"Melanoma treatment in review","volume":"7","author":"Domingues","year":"2018","journal-title":"Immuno Targets Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ijc.25683","article-title":"How to kill tumor cells with inhibitors of poly(ADP-ribosyl)ation","volume":"128","author":"Mangerich","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1042\/BST20180418","article-title":"PARPs in genome stability and signal transduction: Implications for cancer therapy","volume":"46","author":"Palazzo","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nchembio.2568","article-title":"Insights into the biogenesis, function, and regulation of ADP-ribosylation","volume":"14","author":"Cohen","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nrm.2017.53","article-title":"The multifaceted roles of PARP1 in DNA repair and chromatin remodelling","volume":"18","author":"Ray","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.imr.2014.09.005","article-title":"Antagonistic crosstalk between SIRT1, PARP-1, and -2 in the regulation of chronic in-flammation associated with aging and metabolic diseases","volume":"3","author":"Chung","year":"2014","journal-title":"Integr. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the No-menclature committee on cell death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death. Differ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1007\/s00018-002-8527-2","article-title":"The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders","volume":"59","author":"Hassa","year":"2002","journal-title":"Cell Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molcel.2010.06.017","article-title":"The PARP side of the nucleus: Molecular actions, physiological outcomes, and clinical targets","volume":"39","author":"Krishnakumar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7573\/dic.212540","article-title":"Advances in the use of PARP inhibitor therapy for breast cancer","volume":"7","author":"McCann","year":"2018","journal-title":"Drugs Context"},{"key":"ref_17","first-page":"2641712","article-title":"PARP1 and Poly(ADP-ribosyl)ation signaling during Au-tophagy in response to nutrient deprivation","volume":"2019","author":"Dantzer","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/1541-7786.MCR-13-0672","article-title":"Transcriptional roles of PARP1 in cancer","volume":"12","author":"Schiewer","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3390\/cancers5030943","article-title":"PARP-1: Friend or Foe of DNA damage and repair in tumorigenesis?","volume":"5","author":"Swindall","year":"2013","journal-title":"Cancers"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.5604\/17322693.1119792","article-title":"Synthetic lethality as a functional tool in basic research and in anticancer therapy","volume":"68","author":"Toma","year":"2014","journal-title":"Post\u0119py Higieny Medycyny Do\u015bwiadczalnej"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111","DOI":"10.5114\/fn.2014.43782","article-title":"Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index cor-relates with tumour grade in meningiomas","volume":"52","author":"Csonka","year":"2014","journal-title":"Folia Neuropathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"46348","DOI":"10.18632\/oncotarget.18013","article-title":"PARP1 expression and its correlation with survival is tu-mour molecular subtype dependent in glioblastoma","volume":"8","author":"Kouhsari","year":"2017","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1053\/j.gastro.2005.03.007","article-title":"Poly(ADP-ribose) polymerase-1 is a component of the oncogenic T-cell factor-4\/beta-catenin complex","volume":"128","author":"Idogawa","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e8816","DOI":"10.15252\/emmm.201708816","article-title":"PARP-1 regulates DNA repair factor availability","volume":"10","author":"Schiewer","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.3892\/ol.2016.5226","article-title":"PARP-1 may be involved in angiogenesis in epithelial ovarian cancer","volume":"12","author":"Wei","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rodriguez, M.I., Peralta-Leal, A., O\u2019Valle, F., Rodriguez-Vargas, J.M., Gonzalez-Flores, A., Majuelos-Melguizo, J., L\u00f3pez, L., Serrano, S., De Herreros, A.G., and Rodr\u00edguez-Manzaneque, J.C. (2013). PARP-1 Regulates metastatic melanoma through modulation of vimentin-induced malignant transformation. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003531"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1158\/1535-7163.MCT-13-0010","article-title":"PARP1 Is overexpressed in nasopharyngeal carcinoma and its inhibition enhances radiotherapy","volume":"12","author":"Chow","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.pharmthera.2018.03.006","article-title":"Double-barreled gun: Combination of PARP inhibitor with conventional chemo-therapy","volume":"188","author":"Lu","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pulliam, N., Tang, J., Wang, W., Fang, F., Sood, R., O\u2019Hagan, H.M., Miller, K.D., Clarke, R.B., and Nephew, K.P. (2019). Poly-ADP-ribosylation of estrogen receptor-alpha by PARP1 mediates antiestrogen resistance in human breast cancer cells. Cancers, 11.","DOI":"10.3390\/cancers11010043"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utiliz-ing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","article-title":"Electrophoretic transfer of proteins from polyacrylamide gels to nitrocel-lulose sheets: Procedure and some applications","volume":"76","author":"Towbin","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kupczyk, P., Reich, A., Gajda, M., Ho\u0142ysz, M., Wysoki\u0144ska, E., Paprocka, M., Szepietowski, J.C., Jagodzi\u0144ski, P.P., Zi\u00f3\u0142kowski, P., and Szepietowski, J.C. (2018). UCHL1\/PGP 9.5 dynamic in neuro-immune-cutaneous milieu: Focus-ing on axonal nerve terminals and epidermal keratinocytes in psoriatic itch. Biomed. Res. Int., 2018.","DOI":"10.1155\/2018\/7489316"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.3390\/cells9051135","article-title":"Up-regulation of PARP1 expression significantly correlated with poor sur-vival in mucosal melanomas","volume":"9","author":"Donizy","year":"2020","journal-title":"Cells"},{"key":"ref_36","unstructured":"Kassambara, A., Kosinski, M., and Biecek, P. (2020, March 12). Survminer: Drawing Survival Curves Using \u201cggplot\u201d. Available online: https:\/\/cran.r-project.org\/package=survminer."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Simiczyjew, A., Pietraszek-Gremplewicz, K., Dratkiewicz, E., Podg\u00f3rska, M., Matkowski, R., Zi\u0119tek, M., and Nowak, D. (2019). Combination of selected MET and EGFR inhibitors decreases melanoma cells\u2019 invasive abilities. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01116"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.4081\/ejh.2016.2728","article-title":"Varying effects of EGF, HGF and TGFbeta on formation of invadopodia and invasiveness of melanoma cell lines of different origin","volume":"60","author":"Makowiecka","year":"2016","journal-title":"Eur. J. Histochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.humpath.2005.04.017","article-title":"Poly (adenosine diphosphate-ribose) polymerase 1 expression in malignant melanomas from photoexposed areas of the head and neck region","volume":"36","author":"Staibano","year":"2005","journal-title":"Hum. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1111\/pcmr.12290","article-title":"Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients","volume":"27","author":"Mactier","year":"2014","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1002\/ijc.28796","article-title":"Inherited variation in the PARP1 gene and survival from melanoma","volume":"135","author":"Davies","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7714","DOI":"10.1038\/sj.onc.1209751","article-title":"Differential regulation of CXC ligand 1 transcription in melanoma cell lines by poly (ADP-ribose) polymerase-1","volume":"25","author":"Amiri","year":"2006","journal-title":"Oncogene"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9366","DOI":"10.1074\/jbc.M009897200","article-title":"A role for Poly(ADP-ribose) polymerase in the transcriptional regulation of the melanoma growth stimulatory activity (CXCL1) gene expression","volume":"276","author":"Nirodi","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1038\/s41388-020-1175-x","article-title":"Coordinated signals from PARP-1 and PARP-2 are required to establish a proper T cell immune response to breast tumors in mice","volume":"39","author":"Comerma","year":"2020","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0002-9440(10)65173-5","article-title":"Vascular channel formation by human melanoma cells In Vivo and In Vitro: Vasculogenic mimicry","volume":"155","author":"Maniotis","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_46","first-page":"1149","article-title":"Effect of ABT-888 on the apoptosis, motility and invasive-ness of BRAFi-resistant melanoma cells","volume":"53","author":"Fratangelo","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Raineri, A., Fasoli, S., Campagnari, R., Gotte, G., and Menegazzi, M. (2019). Onconase restores cytotoxicity in dabrafenib-resistant A375 Hu-man melanoma cells and affects cell migration, invasion and colony formation capability. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235980"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.bcp.2019.06.006","article-title":"Influence of onconase in the therapeutic potential of PARP inhibitors in A375 malignant melanoma cells","volume":"167","author":"Raineri","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"De Koning, L., Decaudin, D., el Botty, R., Nicolas, A., Carita, G., Schuller, M., Ouine, B., Cartier, A., Naguez, A., and Fleury, J. (2019). PARP inhibition increases the response to chemotherapy in uveal mela-noma. Cancers, 11.","DOI":"10.3390\/cancers11060751"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6219","DOI":"10.1167\/iovs.11-8853","article-title":"Altered expression of the poly(ADP-ribosyl)ation en-zymes in uveal melanoma and regulation of PARG gene expression by the transcription factor ERM","volume":"53","author":"Simard","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12975","DOI":"10.1074\/jbc.M111.321828","article-title":"CHFR protein regulates mitotic checkpoint by targeting PARP-1 pro-tein for ubiquitination and degradation","volume":"287","author":"Kashima","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ebiom.2018.11.025","article-title":"High PARP-1 expression predicts poor survival in acute myeloid leukemia and PARP-1 inhibitor and SAHA-bendamustine hybrid inhibitor combination treatment synergistically enhances an-ti-tumor effects","volume":"38","author":"Li","year":"2018","journal-title":"Ebiomedicine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1073\/pnas.1209507110","article-title":"Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair","volume":"110","author":"Robu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/286\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:17:57Z","timestamp":1760159877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,31]]},"references-count":53,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cells10020286"],"URL":"https:\/\/doi.org\/10.3390\/cells10020286","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,31]]}}}