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Thrombocytopenia, a common complication among patients with solid tumors, can be life-threatening when it leads to thrombosis. Although routine and frequent transfusion of blood components to those patients effectively improves the outcome of treatment, it brings a huge cost and burden to the health care system. Apoptosis mediated by intrinsic mitochondrial pathways has been well described in platelet clearance in vivo. However, the biological mechanism of thrombocytopenia modulated by mitochondria in tumor patients is unclear. In this paper, the expressions of the excision repair cross-complementing (ERCC) family, a set of proteins in DNA damage repair, are investigated by a bioinformatics analysis. The results presented that the mRNA expression level of 5 genes in the ERCC family has been significantly decreased in platelets from six different tumor patients versus healthy donors. There were no patterns of the downregulation of the ERCC family correlating to specific tumor types among the six test samples. In nucleated cells, cell death mediated by the intrinsic apoptotic pathway occurs when ROS overproduction demolishes the mitochondrial integrity and damages the mitochondrial DNA (mtDNA). Given platelets are anucleate, the expression of the ERCC family to target mtDNA repair is hypothesized.
[1] Best MG, Sol N, Kooi I, Tannous J, Westerman BA, Rustenburg F, Schellen P, Verschueren H, Post E, Koster J, et al. RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics. Cancer Cell. 2015;28(5):666-676.doi: 10.1016/j.ccell.2015.09.018. Epub 2015 Oct 29. PMID: 26525104; PMCID: PMC4644263.
[2] Houghton AR, Gray D. Chamberlain's Symptoms and Signs in Clinical Medicine, An Introduction to Medical Diagnosis (CRC Press); 2010.
[3] Jinna S, Khandhar PB. Thrombocytopenia. StatPearls, 2023. https://www.ncbi.nlm.nih.gov/books/NBK542208/.
[4] Liebman HA. Thrombocytopenia in cancer patients. Thromb Res. 2014;133 Suppl 2:S63-9. doi: 10.1016/S0049-3848(14)50011-4. PMID: 24862148.
[5] Ghanavat M, Ebrahimi M, Rafieemehr H, Maniati M, Behzad MM, Shahrabi S. Thrombocytopenia in solid tumors: Prognostic significance. Oncol Rev. 2019 May 14;13(1):413. doi: 10.4081/oncol.2019.413. PMID: 31205603; PMCID: PMC6542370.
[6] Kuter DJ. Managing thrombocytopenia associated with cancer chemotherapy. Oncology (Williston Park). 2015;29(4):282-94. PMID: 25952492.
[7] Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007 Jun;35(4):495-516.
doi: 10.1080/01926230701320337. PMID: 17562483; PMCID: PMC2117903.
[8] Leytin V. Apoptosis in the anucleate platelet. Blood Rev. 2012;26(2):51-63. doi: 10.1016/j.blre.2011.10.002. Epub 2011 Nov 4. PMID: 22055392.
[9] Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.
doi: 10.1080/01926230701320337. PMID: 17562483; PMCID: PMC2117903.
[10] Tschopp J. Mitochondria: Sovereign of inflammation? Eur J Immunol. 2011;41(5):1196-202. doi: 10.1002/eji.201141436. PMID: 21469137.
[11] Johansson AC, Appelqvist H, Nilsson C, Kågedal K, Roberg K, Ollinger K. Regulation of apoptosis-associated lysosomal mem-brane permeabilization. Apoptosis. 2010;15(5):527-40.
doi: 10.1007/s10495-009-0452-5. PMID: 20077016; PMCID: PMC2850995.
[12] Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005;309(5733):481-4. doi: 10.1126/science.1112125. PMID: 16020738.
[13] Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005;308(5730):1909-11. doi: 10.1126/science.1106653. Epub 2005 May 5. PMID: 15879174.
[14] Marteijn JA, Lans H, Vermeulen W, Hoeijmakers JH. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 2014;15(7):465-481.
[15] O'Donovan A, Davies AA, Moggs JG, West SC, Wood RD. XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair. Nature. 1994;371:432-435.
[16] Fagbemi AF, Orelli B, Schärer OD. Regulation of endonuclease activity in human nucleotide excision repair. DNA Repair (Amst). 2011;10(7):722-729.
[17] Faridounnia M, Folkers GE, Boelens R. Function and Interactions of ERCC1-XPF in DNA Damage Response. Molecules. 2018;23(12):3205. doi: 10.3390/molecules23123205. PMID: 30563071; PMCID: PMC6320978.
[18] Melis JP, van Steeg H, Luijten M. Oxidative DNA damage and nucleotide excision repair. Antioxid Redox Signal. 2013;18(18):2409-19. doi: 10.1089/ars.2012.5036. Epub 2012 Dec 7. PMID: 23216312; PMCID: PMC3671630.
[19] Xiang Y, Xiang P, Zhang L, Li Y, Zhang J. A narrative review for platelets and their RNAs in cancers: New concepts and clinical perspectives. Medicine (Baltimore). 2022;101(52):e32539. doi: 10.1097/MD.0000000000032539. PMID: 36596034; PMCID: PMC9803462.
[20] Agidigbi TS, Kim C. Reactive Oxygen Species in Osteoclast Differentiation and Possible Pharmaceutical Targets of ROS-Mediated Osteoclast Diseases. Int J Mol Sci. 2019;20(14):3576. doi: 10.3390/ijms20143576. PMID: 31336616; PMCID: PMC6678498.
[21] Shokolenko IN, Wilson GL, Alexeyev MF. Aging: A mitochondrial DNA perspective, critical analysis and an update. World J Exp Med. 2014;4(4):46-57. doi: 10.5493/wjem.v4.i4.46. PMID: 25414817; PMCID: PMC4237642.
[22] Papatheodorou I, Moreno P, Manning J, Fuentes AM, George N, Fexova S, Fonseca NA, Füllgrabe A, Green M, Huang N, et al. Expression Atlas update: from tissues to single cells. Nucleic Acids Res. 2020;48(D1):D77-D83. doi: 10.1093/nar/gkz947. PMID: 31665515; PMCID: PMC7145605.
[23] Kapushesky M, Emam I, Holloway E, Kurnosov P, Zorin A, Malone J, Rustici G, Williams E, Parkinson H, Brazma A. Gene expression atlas at the European bioinformatics institute. Nucleic Acids Res. 2010;38(Database issue):D690-8.
doi: 10.1093/nar/gkp936. Epub 2009 Nov 11. PMID: 19906730; PMCID: PMC2808905.
[24] Petryszak R, Burdett T, Fiorelli B, Fonseca NA, Gonzalez-Porta M, Hastings E, Huber W, Jupp S, Keays M, Kryvych N, et al. Expression Atlas update—a database of gene and transcript expression from microarray- and sequencing-based functional genomics experiments. Nucleic Acids Res. 2014;42(Database issue):D926-32. doi: 10.1093/nar/gkt1270. Epub 2013 Dec 4. PMID: 24304889; PMCID: PMC3964963.
[25] Petryszak R, Keays M, Tang YA, Fonseca NA, Barrera E, Burdett T, Füllgrabe A, Fuentes AM, Jupp S, Koskinen S, et al. Expression Atlas update—an integrated database of gene and protein expression in humans, animals and plants. Nucleic Acids Res. 2016;44(D1):D746-52. doi: 10.1093/nar/gkv1045. Epub 2015 Oct 19. PMID: 26481351; PMCID: PMC4702781.
[26] Ghanavat M, Ebrahimi M, Rafieemehr H, Maniati M, Behzad MM, Shahrabi S. Thrombocytopenia in solid tumors: Prognostic significance. Oncol Rev. 2019;13(1):413. doi: 10.4081/oncol.2019.413. PMID: 31205603; PMCID: PMC6542370.
[27] LeBrasseur N. Platelets' preset lifespan. J Cell Biol. 2007;177(2):186. doi: 10.1083/jcb.1772rr5. PMCID: PMC2064146.
[28] Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res. 2010;44(5):479-96. doi: 10.3109/10715761003667554. PMID: 20370557; PMCID: PMC3880197.
[29] Melchinger H, Jain K, Tyagi T, Hwa J. Role of Platelet Mitochondria: Life in a Nucleus-Free Zone. Front Cardiovasc Med. 2019;6:153. doi: 10.3389/fcvm.2019.00153. PMID: 31737646; PMCID: PMC6828734.
[30] Hekimi S, Wang Y, Noë A. Mitochondrial ROS and the effectors of the intrinsic apoptotic pathway in aging cells: the discerning killers! Front Genet. 2016;7:161. doi: 10.3389/fgene.2016.00161.
[31] Manandhar M, Boulware KS, Wood RD. The ERCC1 and ERCC4 (XPF) genes and gene products. Gene. 2015;569(2):153-61. doi: 10.1016/j.gene.2015.06.026. Epub 2015 Jun 12. PMID: 26074087; PMCID: PMC4536074.
[32] Rong Z, Tu P, Xu P, Sun Y, Yu F, Tu N, Guo L, Yang Y. The Mitochondrial Response to DNA Damage. Front Cell Dev Biol. 2021;9:669379. doi: 10.3389/fcell.2021.669379. PMID: 34055802; PMCID: PMC8149749.
[33] Liao S, Chen L, Song Z, He H. The fate of damaged mitochondrial DNA in the cell. Biochim Biophys Acta Mol Cell Res. 2022;1869(5):119233. doi: 10.1016/j.bbamcr.2022.119233. Epub 2022 Feb 5. PMID: 35131372.
[34] ERCC5 ERCC excision repair 5, endonuclease [Homo sapiens (human)]. National Center for Biotechnology Information; 2024. https://www.ncbi.nlm.nih.gov/gene/2073.
[35] ERCC6L2 ERCC excision repair 6 like 2 [Homo sapiens (human)]. National Center for Biotechnology Information; 2024. https://www.ncbi.nlm.nih.gov/gene/375748.
[36] ERCC6 ERCC excision repair 6, chromatin remodeling factor [Homo sapiens (human)]. National Center for Biotechnology Information; 2024. https://www.ncbi.nlm.nih.gov/gene/2074.
[37] ERCC8 ERCC excision repair 8, CSA ubiquitin ligase complex subunit [Homo sapiens (human)]. National Center for Biotechnology Information; 2024. https://www.ncbi.nlm.nih.gov/gene/1161.
[38] Koussounadis A, Langdon SP, Um IH, Harrison DJ, Smith VA. Relationship between differentially expressed mRNA and mRNA–protein correlations in a xenograft model system. Sci Rep. 2015;5:10775. doi: 10.1038/srep10775.
Regulation of Tumor-induced Platelet Clearance Modulated by the ERCC Family Through Mitochondrial Pathway
How to cite this paper: Zihe Qi. (2024) Regulation of Tumor-induced Platelet Clearance Modulated by the ERCC Family Through Mitochondrial Pathway. International Journal of Clinical and Experimental Medicine Research, 8(4), 663-669.
DOI: https://dx.doi.org/10.26855/ijcemr.2024.10.021