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Current Cancer Drug Targets

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ISSN (Online): 1873-5576

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Research Article

Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions

Author(s): Reza Vazifehmand, Dhuha Saeed Ali, Foroozandeh Monem Homaie, Fatemeh Molaei Jalalvand, Zulkefley Othman, Chau Deming, Johnson Stanslas and Zamberi Sekawi*

Volume 24, Issue 12, 2024

Published on: 13 February, 2024

Page: [1262 - 1274] Pages: 13

DOI: 10.2174/0115680096274769240115165344

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion.

Objective: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions.

Methods: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways.

Results: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments.

Conclusion: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments.

Keywords: HSV-G47Δ, telomerase, telomere length, hypoxia, normoxia, U251-glioblastoma cancer stem cells, central nervous system (CNS).

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[1]
Holland, E.C. Glioblastoma multiforme: The terminator. Proc. Natl. Acad. Sci., 2000, 97(12), 6242-6244.
[http://dx.doi.org/10.1073/pnas.97.12.6242] [PMID: 10841526]
[2]
Schwartzbaum, J.A.; Fisher, J.L.; Aldape, K.D.; Wrensch, M. Epidemiology and molecular pathology of glioma. Nat. Clin. Pract. Neurol., 2006, 2(9), 494-503.
[http://dx.doi.org/10.1038/ncpneuro0289] [PMID: 16932614]
[3]
Agnihotri, S.; Burrell, K.E.; Wolf, A.; Jalali, S.; Hawkins, C.; Rutka, J.T.; Zadeh, G. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Arch. Immunol. Ther. Exp., 2013, 61(1), 25-41.
[http://dx.doi.org/10.1007/s00005-012-0203-0] [PMID: 23224339]
[4]
Ostrom, Q.T.; Gittleman, H.; Fulop, J.; Liu, M.; Blanda, R.; Kromer, C.; Wolinsky, Y.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro-oncol., 2015, 17(S4), iv1-iv62.
[http://dx.doi.org/10.1093/neuonc/nov189] [PMID: 26511214]
[5]
Grochans, S.; Cybulska, A.M.; Simińska, D.; Korbecki, J.; Kojder, K.; Chlubek, D.; Baranowska-Bosiacka, I. Epidemiology of glioblastoma multiforme–literature review. Cancers, 2022, 14(10), 2412.
[http://dx.doi.org/10.3390/cancers14102412] [PMID: 35626018]
[6]
Ostrom, Q.T.; Cioffi, G.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro-oncol., 2021, 23(12), iii1-iii105.
[http://dx.doi.org/10.1093/neuonc/noab200] [PMID: 34608945]
[7]
Mohammed, S.; Dinesan, M.; Ajayakumar, T. Survival and quality of life analysis in glioblastoma multiforme with adjuvant chemoradiotherapy: A retrospective study. Rep. Pract. Oncol. Radiother., 2022, 27(6), 1026-1036.
[http://dx.doi.org/10.5603/RPOR.a2022.0113]
[8]
Simińska, D.; Korbecki, J.; Kojder, K.; Kapczuk, P.; Fabiańska, M.; Gutowska, I.; Machoy-Mokrzyńska, A.; Chlubek, D.; Baranowska-Bosiacka, I. Epidemiology of anthropometric factors in glioblastoma multiforme—Literature review. Brain Sci., 2021, 11(1), 116.
[http://dx.doi.org/10.3390/brainsci11010116] [PMID: 33467126]
[9]
Esemen, Y.; Awan, M.; Parwez, R.; Baig, A.; Rahman, S.; Masala, I.; Franchini, S.; Giakoumettis, D. Molecular pathogenesis of glioblastoma in adults and future perspectives: A systematic review. Int. J. Mol. Sci., 2022, 23(5), 2607.
[http://dx.doi.org/10.3390/ijms23052607] [PMID: 35269752]
[10]
Claus, E.B.; Cannataro, V.L.; Gaffney, S.G.; Townsend, J.P. Environmental and sex-specific molecular signatures of glioma causation. Neuro-oncol., 2022, 24(1), 29-36.
[http://dx.doi.org/10.1093/neuonc/noab103] [PMID: 33942853]
[11]
Czarnywojtek, A.; Borowska, M.; Dyrka, K.; Van Gool, S.; Sawicka-Gutaj, N.; Moskal, J.; Ruchała, M. Glioblastoma multiforme: The latest diagnostics and treatment techniques. Pharmacology, 2023, 17, 1-9.
[12]
Rodríguez-Camacho, A.; Flores-Vázquez, J.G.; Moscardini-Martelli, J.; Torres-Ríos, J.A.; Olmos-Guzmán, A.; Ortiz-Arce, C.S.; Cid-Sánchez, D.R.; Pérez, S.R.; Macías-González, M.D.S.; Hernández-Sánchez, L.C.; Heredia-Gutiérrez, J.C.; Contreras-Palafox, G.A.; Suárez-Campos, J.J.E.; Celis-López, M.Á.; Gutiérrez-Aceves, G.A.; Moreno-Jiménez, S. Glioblastoma treatment: State-of-the-art and future perspectives. Int. J. Mol. Sci., 2022, 23(13), 7207.
[http://dx.doi.org/10.3390/ijms23137207] [PMID: 35806212]
[13]
Vescovi, A.L.; Galli, R.; Reynolds, B.A. Brain tumour stem cells. Nat. Rev. Cancer, 2006, 6(6), 425-436.
[http://dx.doi.org/10.1038/nrc1889] [PMID: 16723989]
[14]
Yuan, X.; Curtin, J.; Xiong, Y.; Liu, G.; Waschsmann-Hogiu, S.; Farkas, D.L.; Black, K.L.; Yu, J.S. Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene, 2004, 23(58), 9392-9400.
[http://dx.doi.org/10.1038/sj.onc.1208311] [PMID: 15558011]
[15]
Vaupel, P.; Mayer, A. Hypoxia in cancer: Significance and impact on clinical outcome. Cancer Metastasis Rev., 2007, 26(2), 225-239.
[http://dx.doi.org/10.1007/s10555-007-9055-1] [PMID: 17440684]
[16]
Galli, R.; Binda, E.; Orfanelli, U.; Cipelletti, B.; Gritti, A.; De Vitis, S.; Fiocco, R.; Foroni, C.; Dimeco, F.; Vescovi, A. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res., 2004, 64(19), 7011-7021.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1364] [PMID: 15466194]
[17]
Lee, J.; Kotliarova, S.; Kotliarov, Y.; Li, A.; Su, Q.; Donin, N.M.; Pastorino, S.; Purow, B.W.; Christopher, N.; Zhang, W.; Park, J.K.; Fine, H.A. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell, 2006, 9(5), 391-403.
[http://dx.doi.org/10.1016/j.ccr.2006.03.030] [PMID: 16697959]
[18]
Marian, C.O.; Cho, S.K.; Mcellin, B.M.; Maher, E.A.; Hatanpaa, K.J.; Madden, C.J.; Mickey, B.E.; Wright, W.E.; Shay, J.W.; Bachoo, R.M. The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth. Clin. Cancer Res., 2010, 16(1), 154-163.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2850] [PMID: 20048334]
[19]
Blasco, M.A. Telomere length, stem cells and aging. Nat. Chem. Biol., 2007, 3(10), 640-649.
[http://dx.doi.org/10.1038/nchembio.2007.38] [PMID: 17876321]
[20]
Blackburn, E.H. Telomeres and telomerase: The means to the end (Nobel lecture). Angew. Chem. Int. Ed., 2010, 49(41), 7405-7421.
[http://dx.doi.org/10.1002/anie.201002387] [PMID: 20821774]
[21]
Xin, H.; Liu, D.; Songyang, Z. The telosome/shelterin complex and its functions. Genome Biol., 2008, 9(9), 232.
[http://dx.doi.org/10.1186/gb-2008-9-9-232] [PMID: 18828880]
[22]
Diotti, R.; Loayza, D. Shelterin complex and associated factors at human telomeres. Nucleus, 2011, 2(2), 119-135.
[http://dx.doi.org/10.4161/nucl.2.2.15135] [PMID: 21738835]
[23]
Greider, C.W. Telomerase discovery: the excitement of putting together pieces of the puzzle (Nobel lecture). Angew. Chem. Int. Ed., 2010, 49(41), 7422-7439.
[http://dx.doi.org/10.1002/anie.201002408] [PMID: 20872384]
[24]
Guan, J.Z.; Guan, W.P.; Maeda, T.; Makino, N. Different levels of hypoxia regulate telomere length and telomerase activity. Aging Clin. Exp. Res., 2012, 24(3), 213-217.
[http://dx.doi.org/10.1007/BF03325250] [PMID: 23114548]
[25]
Hiraga, S.; Ohnishi, T.; Izumoto, S.; Miyahara, E.; Kanemura, Y.; Matsumura, H.; Arita, N. Telomerase activity and alterations in telomere length in human brain tumors. Cancer Res., 1998, 58(10), 2117-2125.
[PMID: 9605755]
[26]
Hanif, F.; Muzaffar, K.; Perveen, K.; Malhi, S.M.; Simjee, ShU. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pacific journal of cancer prevention. APJCP, 2017, 18(1), 3-9.
[http://dx.doi.org/10.22034/APJCP.2017.18.1.3] [PMID: 28239999]
[27]
Picariello, L.; Grappone, C.; Polvani, S.; Galli, A. Telomerase activity: An attractive target for cancer therapeutics. World J. Pharmacol., 2014, 3(4), 86-96.
[http://dx.doi.org/10.5497/wjp.v3.i4.86]
[28]
Wollmann, G.; Ozduman, K.; van den Pol, A.N. Oncolytic virus therapy for glioblastoma multiforme: concepts and candidates. Cancer J., 2012, 18(1), 69-81.
[http://dx.doi.org/10.1097/PPO.0b013e31824671c9] [PMID: 22290260]
[29]
Fukuhara, H.; Martuza, R.L.; Rabkin, S.D.; Ito, Y.; Todo, T. Oncolytic herpes simplex virus vector g47delta in combination with androgen ablation for the treatment of human prostate adenocarcinoma. Clin. Cancer Res., 2005, 11(21), 7886-7890.
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1090] [PMID: 16278413]
[30]
Vazifehmand, R.; Ali, D.S.; Othman, Z.; Chau, D.M.; Stanslas, J.; Shafa, M.; Sekawi, Z. The evaluation expression of non-coding RNAs in response to HSV-G47∆ oncolytic virus infection in glioblastoma multiforme cancer stem cells. J. Neurovirol., 2022, 28(4-6), 566-582.
[http://dx.doi.org/10.1007/s13365-022-01089-w] [PMID: 35951174]
[31]
Wang, J.; Xu, L.; Zeng, W.; Hu, P.; Zeng, M.; Rabkin, S.D.; Liu, R. Treatment of human hepatocellular carcinoma by the oncolytic herpes simplex virus G47delta. Cancer Cell Int., 2014, 14(1), 83.
[http://dx.doi.org/10.1186/s12935-014-0083-y] [PMID: 25360068]
[32]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262]
[33]
Lirussi, L.; Nilsen, H. Telomere maintenance: regulating hTERC fate through RNA modifications. Mol. Cell. Oncol., 2019, 6(6), e1670489.
[http://dx.doi.org/10.1080/23723556.2019.1670489] [PMID: 31692866]
[34]
Leão, R.; Apolónio, J.D.; Lee, D.; Figueiredo, A.; Tabori, U.; Castelo-Branco, P. Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer. J. Biomed. Sci., 2018, 25(1), 22.
[http://dx.doi.org/10.1186/s12929-018-0422-8] [PMID: 29526163]
[35]
Yang, R.; Han, Y.; Guan, X.; Hong, Y.; Meng, J.; Ding, S.; Long, Q.; Yi, W. Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer. Cell Commun. Signal., 2023, 21(1), 218.
[http://dx.doi.org/10.1186/s12964-023-01244-8] [PMID: 37612721]
[36]
Yik, M.Y.; Azlan, A.; Rajasegaran, Y.; Rosli, A.; Yusoff, N.M.; Moses, E.J. Mechanism of human telomerase reverse transcriptase (hTERT) regulation and clinical impacts in leukemia. Genes, 2021, 12(8), 1188.
[http://dx.doi.org/10.3390/genes12081188] [PMID: 34440361]
[37]
Jin, D.H.; Kim, S.; Kim, D.H.; Park, J. Two genetic variants in telomerase-associated protein 1 are associated with stomach cancer risk. J Hum Genet, 2016, 61(10), 885-889.
[http://dx.doi.org/10.1038/jhg.2016.71]
[38]
Kan, G.; Wang, Z.; Sheng, C.; Yao, C.; Mao, Y.; Chen, S. Inhibition of DKC1 induces telomere-related senescence and apoptosis in lung adenocarcinoma. J. Transl. Med., 2021, 19(1), 161.
[http://dx.doi.org/10.1186/s12967-021-02827-0] [PMID: 33879171]
[39]
Chu, C.M.; Yu, H.H.; Kao, T.L.; Chen, Y.H.; Lu, H.H.; Wu, E.T.; Yang, Y.L.; Lin, C.H.; Lin, S.Y.; Tsai, M.J.M.; Chien, Y.H.; Hwu, W.L.; Chen, W.P.; Lee, N.C.; Tseng, C.K. A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome. NPJ Genom. Med., 2022, 7(1), 64.
[http://dx.doi.org/10.1038/s41525-022-00335-8] [PMID: 36309505]
[40]
Iwano, T.; Tachibana, M.; Reth, M.; Shinkai, Y. Importance of TRF1 for functional telomere structure. J. Biol. Chem., 2004, 279(2), 1442-1448.
[http://dx.doi.org/10.1074/jbc.M309138200] [PMID: 14559908]
[41]
van Steensel, B.; de Lange, T. Control of telomere length by the human telomeric protein TRF1. Nature, 1997, 385(6618), 740-743.
[http://dx.doi.org/10.1038/385740a0] [PMID: 9034193]
[42]
Wang, L.; Tu, Z.; Liu, C.; Liu, H.; Kaldis, P.; Chen, Z.; Li, W. Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis. Cell Death Differ., 2018, 25(6), 1174-1188.
[http://dx.doi.org/10.1038/s41418-017-0037-8] [PMID: 29311622]
[43]
Li, H.L.; Song, J.; Yong, H.M.; Hou, P.F.; Chen, Y.S.; Song, W.B.; Bai, J.; Zheng, J.N. PinX1: Structure, regulation and its functions in cancer. Oncotarget, 2016, 7(40), 66267-66275.
[http://dx.doi.org/10.18632/oncotarget.11411] [PMID: 27556185]
[44]
Cheung, D.H.C.; Kung, H.F.; Huang, J.J.; Shaw, P.C. PinX1 is involved in telomerase recruitment and regulates telomerase function by mediating its localization. FEBS Lett., 2012, 586(19), 3166-3171.
[http://dx.doi.org/10.1016/j.febslet.2012.06.028] [PMID: 22749911]
[45]
Yoo, J.E.; Park, Y.N.; Oh, B.K. PinX1, a telomere repeat-binding factor 1 (TRF1)-interacting protein, maintains telomere integrity by modulating TRF1 homeostasis, the process in which human telomerase reverse Transcriptase (hTERT) plays dual roles. J. Biol. Chem., 2014, 289(10), 6886-6898.
[http://dx.doi.org/10.1074/jbc.M113.506006] [PMID: 24415760]
[46]
Savage, S.A.; Giri, N.; Baerlocher, G.M.; Orr, N.; Lansdorp, P.M.; Alter, B.P. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am. J. Hum. Genet., 2008, 82(2), 501-509.
[http://dx.doi.org/10.1016/j.ajhg.2007.10.004] [PMID: 18252230]
[47]
Frank, A.K.; Tran, D.C.; Qu, R.W.; Stohr, B.A.; Segal, D.J.; Xu, L. The shelterin TIN2 subunit mediates recruitment of telomerase to telomeres. PLoS Genet., 2015, 11(7), e1005410.
[http://dx.doi.org/10.1371/journal.pgen.1005410] [PMID: 26230315]
[48]
Aramburu, T.; Plucinsky, S.; Skordalakes, E. POT1-TPP1 telomere length regulation and disease. Comput. Struct. Biotechnol. J., 2020, 18, 1939-1946.
[http://dx.doi.org/10.1016/j.csbj.2020.06.040] [PMID: 32774788]
[49]
Gu, P.; Jia, S.; Takasugi, T.; Tesmer, V.M.; Nandakumar, J.; Chen, Y.; Chang, S. Distinct functions of POT1 proteins contribute to the regulation of telomerase recruitment to telomeres. Nat. Commun., 2021, 12(1), 5514.
[http://dx.doi.org/10.1038/s41467-021-25799-7] [PMID: 34535663]
[50]
Kelleher, C.; Kurth, I.; Lingner, J. Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro. Mol. Cell. Biol., 2005, 25(2), 808-818.
[http://dx.doi.org/10.1128/MCB.25.2.808-818.2005] [PMID: 15632080]
[51]
van Steensel, B.; Smogorzewska, A.; de Lange, T. TRF2 protects human telomeres from end-to-end fusions. Cell, 1998, 92(3), 401-413.
[http://dx.doi.org/10.1016/S0092-8674(00)80932-0] [PMID: 9476899]
[52]
Imran, S.A.M.; Yazid, M.D.; Cui, W.; Lokanathan, Y. The intra-and extra-telomeric role of TRF2 in the DNA damage response. Int. J. Mol. Sci., 2021, 22(18), 9900.
[http://dx.doi.org/10.3390/ijms22189900] [PMID: 34576063]
[53]
Kim, H.; Lee, O.H.; Xin, H.; Chen, L.Y.; Qin, J.; Chae, H.K.; Lin, S.Y.; Safari, A.; Liu, D.; Songyang, Z. TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs. Nat. Struct. Mol. Biol., 2009, 16(4), 372-379.
[http://dx.doi.org/10.1038/nsmb.1575] [PMID: 19287395]
[54]
Deng, Y.; Guo, X.; Ferguson, D.O.; Chang, S. Multiple roles for MRE11 at uncapped telomeres. Nature, 2009, 460(7257), 914-918.
[http://dx.doi.org/10.1038/nature08196] [PMID: 19633651]
[55]
Chai, W.; Sfeir, A.J.; Hoshiyama, H.; Shay, J.W.; Wright, W.E. The involvement of the Mre11/Rad50/Nbs1 complex in the generation of G-overhangs at human telomeres. EMBO Rep., 2006, 7(2), 225-230.
[http://dx.doi.org/10.1038/sj.embor.7400600] [PMID: 16374507]
[56]
Saito, Y.; Fujimoto, H.; Kobayashi, J. Role of NBS1 in DNA damage response and its relationship with cancer development. Transl. Cancer Res., 2013, 2(3), 178-189.
[http://dx.doi.org/10.3978/j.issn.2218-676X.2013.04.05]
[57]
Bian, L.; Meng, Y.; Zhang, M.; Li, D. MRE11-RAD50-NBS1 complex alterations and DNA damage response: implications for cancer treatment. Mol. Cancer, 2019, 18(1), 169.
[http://dx.doi.org/10.1186/s12943-019-1100-5] [PMID: 31767017]
[58]
Rai, R.; Chen, Y.; Lei, M.; Chang, S. TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Nat. Commun., 2016, 7(1), 10881.
[http://dx.doi.org/10.1038/ncomms10881] [PMID: 26941064]
[59]
Lototska, L.; Yue, J.X.; Li, J.; Giraud-Panis, M.J.; Songyang, Z.; Royle, N.J.; Liti, G.; Ye, J.; Gilson, E.; Mendez-Bermudez, A. Human RAP 1 specifically protects telomeres of senescent cells from DNA damage. EMBO Rep., 2020, 21(4), e49076.
[http://dx.doi.org/10.15252/embr.201949076] [PMID: 32096305]
[60]
Manandhar, M.; Boulware, K.S.; Wood, R.D. The ERCC1 and ERCC4 (XPF) genes and gene products. Gene, 2015, 569(2), 153-161.
[http://dx.doi.org/10.1016/j.gene.2015.06.026] [PMID: 26074087]
[61]
McDaniel, L.D.; Schultz, R.A. XPF/ERCC4 and ERCC1: Their products and biological roles. Adv Exp Med Biol, 2008, 637, 65-82.
[http://dx.doi.org/10.1007/978-0-387-09599-8_8]
[62]
Guh, C.Y.; Shen, H.J.; Chen, L.W.; Chiu, P.C.; Liao, I.H.; Lo, C.C.; Chen, Y.; Hsieh, Y.H.; Chang, T.C.; Yen, C.P.; Chen, Y.Y.; Chen, T.W.W.; Chen, L.Y.; Wu, C.S.; Egly, J.M.; Chu, H.P.C. XPF activates break-induced telomere synthesis. Nat. Commun., 2022, 13(1), 5781.
[http://dx.doi.org/10.1038/s41467-022-33428-0] [PMID: 36184605]
[63]
Vannier, J.B.; Depeiges, A.; White, C.; Gallego, M.E. Two roles for Rad50 in telomere maintenance. EMBO J., 2006, 25(19), 4577-4585.
[http://dx.doi.org/10.1038/sj.emboj.7601345] [PMID: 16990794]
[64]
Wu, Y.; Xiao, S.; Zhu, X.D. MRE11–RAD50–NBS1 and ATM function as co-mediators of TRF1 in telomere length control. Nat. Struct. Mol. Biol., 2007, 14(9), 832-840.
[http://dx.doi.org/10.1038/nsmb1286] [PMID: 17694070]
[65]
Aghi, M.K.; Liu, T.C.; Rabkin, S.; Martuza, R.L. Hypoxia enhances the replication of oncolytic herpes simplex virus. Mol. Ther., 2009, 17(1), 51-56.
[http://dx.doi.org/10.1038/mt.2008.232] [PMID: 18957963]
[66]
Sgubin, D.; Wakimoto, H.; Kanai, R.; Rabkin, S.D.; Martuza, R.L. Oncolytic herpes simplex virus counteracts the hypoxia-induced modulation of glioblastoma stem-like cells. Stem Cells Transl. Med., 2012, 1(4), 322-332.
[http://dx.doi.org/10.5966/sctm.2011-0035] [PMID: 23197811]
[67]
Deng, Z.; Kim, E.T.; Vladimirova, O.; Dheekollu, J.; Wang, Z.; Newhart, A.; Liu, D.; Myers, J.L.; Hensley, S.E.; Moffat, J.; Janicki, S.M.; Fraser, N.W.; Knipe, D.M.; Weitzman, M.D.; Lieberman, P.M. HSV-1 remodels host telomeres to facilitate viral replication. Cell Rep., 2014, 9(6), 2263-2278.
[http://dx.doi.org/10.1016/j.celrep.2014.11.019] [PMID: 25497088]
[68]
Kim, Y.D.; Jang, S.J.; Lim, E.J.; Ha, J.S.; Shivakumar, S.B.; Jeong, G.J.; Rho, G.J.; Jeon, B.G. Induction of telomere shortening and cellular apoptosis by sodium meta-arsenite in human cancer cell lines. Anim. Cells Syst., 2017, 21(4), 241-254.
[http://dx.doi.org/10.1080/19768354.2017.1342691] [PMID: 30460075]
[69]
Fischer, P.M. The use of CDK inhibitors in oncology: A pharmaceutical perspective. Cell Cycle, 2004, 3(6), 740-744.
[http://dx.doi.org/10.4161/cc.3.6.937] [PMID: 15118410]
[70]
Shervington, A.; Patel, R.; Lu, C.; Cruickshanks, N.; Lea, R.; Roberts, G.; Dawson, T.; Shervington, L. Telomerase subunits expression variation between biopsy samples and cell lines derived from malignant glioma. Brain Res., 2007, 1134(1), 45-52.
[http://dx.doi.org/10.1016/j.brainres.2006.11.093] [PMID: 17196947]
[71]
Miao, F.; Chu, K.; Chen, H.; Zhang, M.; Shi, P.; Bai, J.; You, Y. Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion. Invest. New Drugs, 2019, 37(6), 1177-1186.
[http://dx.doi.org/10.1007/s10637-019-00748-w] [PMID: 30847721]
[72]
Bhari, V.K.; Kumar, D.; Kumar, S.; Mishra, R. Shelterin complex gene: Prognosis and therapeutic vulnerability in cancer. Biochem. Biophys. Rep., 2021, 26, 100937.
[http://dx.doi.org/10.1016/j.bbrep.2021.100937] [PMID: 33553693]
[73]
Liu, Y.; Snow, B.E.; Hande, M.P.; Baerlocher, G.; Kickhoefer, V.A.; Yeung, D.; Wakeham, A.; Itie, A.; Siderovski, D.P.; Lansdorp, P.M.; Robinson, M.O.; Harrington, L. Telomerase-associated protein TEP1 is not essential for telomerase activity or telomere length maintenance in vivo. Mol. Cell. Biol., 2000, 20(21), 8178-8184.
[http://dx.doi.org/10.1128/MCB.20.21.8178-8184.2000] [PMID: 11027287]
[74]
Bhattacharyya, S.; Sandy, A.; Groden, J. Unwinding protein complexes in ALTernative telomere maintenance. J. Cell. Biochem., 2010, 109(1), 7-15.
[http://dx.doi.org/10.1002/jcb.22388] [PMID: 19911388]
[75]
Kickhoefer, V.A.; Siva, A.C.; Kedersha, N.L.; Inman, E.M.; Ruland, C.; Streuli, M.; Rome, L.H. The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J. Cell Biol., 1999, 146(5), 917-928.
[http://dx.doi.org/10.1083/jcb.146.5.917] [PMID: 10477748]
[76]
Bai, Y.; Lathia, J.D.; Zhang, P.; Flavahan, W.; Rich, J.N.; Mattson, M.P. Molecular targeting of TRF2 suppresses the growth and tumorigenesis of glioblastoma stem cells. Glia, 2014, 62(10), 1687-1698.
[http://dx.doi.org/10.1002/glia.22708] [PMID: 24909307]
[77]
Fagagna, F.D.A.D.; Reaper, P.M.; Clay-Farrace, L.; Fiegler, H.; Carr, P.; Von Zglinicki, T.; Jackson, S.P. A DNA damage checkpoint response in telomere-initiated senescence. Nature, 2003, 426(6963), 194-198.
[http://dx.doi.org/10.1038/nature02118]
[78]
Denchi, E.L.; de Lange, T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature, 2007, 448(7157), 1068-1071.
[http://dx.doi.org/10.1038/nature06065] [PMID: 17687332]
[79]
Smogorzewska, A.; de Lange, T. Different telomere damage signaling pathways in human and mouse cells. EMBO J., 2002, 21(16), 4338-4348.
[http://dx.doi.org/10.1093/emboj/cdf433] [PMID: 12169636]
[80]
Sun, C.; Wang, Z.; Song, W.; Chen, B.; Zhang, J.; Dai, X.; Wang, L.; Wu, J.; Lan, Q.; Huang, Q.; Dong, J. Alteration of DNA damage signaling pathway profile in radiation-treated glioblastoma stem-like cells. Oncol. Lett., 2015, 10(3), 1769-1774.
[http://dx.doi.org/10.3892/ol.2015.3411] [PMID: 26622748]
[81]
Gatei, M.; Jakob, B.; Chen, P.; Kijas, A.W.; Becherel, O.J.; Gueven, N.; Birrell, G.; Lee, J.H.; Paull, T.T.; Lerenthal, Y.; Fazry, S.; Taucher-Scholz, G.; Kalb, R.; Schindler, D.; Waltes, R.; Dörk, T.; Lavin, M.F. ATM protein-dependent phosphorylation of Rad50 protein regulates DNA repair and cell cycle control. J. Biol. Chem., 2011, 286(36), 31542-31556.
[http://dx.doi.org/10.1074/jbc.M111.258152] [PMID: 21757780]
[82]
Machida, K.; McNamara, G.; Cheng, K.T.H.; Huang, J.; Wang, C.H.; Comai, L.; Ou, J.H.J.; Lai, M.M.C. Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes. J. Immunol., 2010, 185(11), 6985-6998.
[http://dx.doi.org/10.4049/jimmunol.1000618] [PMID: 20974981]
[83]
Kuroda, S.; Fujiwara, T.; Shirakawa, Y.; Yamasaki, Y.; Yano, S.; Uno, F.; Tazawa, H.; Hashimoto, Y.; Watanabe, Y.; Noma, K.; Urata, Y.; Kagawa, S.; Fujiwara, T. Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. Cancer Res., 2010, 70(22), 9339-9348.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2333] [PMID: 21045143]
[84]
Cong, Y.S.; Wright, W.E.; Shay, J.W. Human telomerase and its regulation. Microbiol. Mol. Biol. Rev., 2002, 66(3), 407-425.
[http://dx.doi.org/10.1128/MMBR.66.3.407-425.2002] [PMID: 12208997]
[85]
Fairall, L.; Chapman, L.; Moss, H.; de Lange, T.; Rhodes, D. Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2. Mol. Cell, 2001, 8(2), 351-361.
[http://dx.doi.org/10.1016/S1097-2765(01)00321-5] [PMID: 11545737]
[86]
Lei, M.; Podell, E.R.; Cech, T.R. Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat. Struct. Mol. Biol., 2004, 11(12), 1223-1229.
[http://dx.doi.org/10.1038/nsmb867] [PMID: 15558049]
[87]
Ye, J.Z.S.; Donigian, J.R.; van Overbeek, M.; Loayza, D.; Luo, Y.; Krutchinsky, A.N.; Chait, B.T.; de Lange, T. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J. Biol. Chem., 2004, 279(45), 47264-47271.
[http://dx.doi.org/10.1074/jbc.M409047200] [PMID: 15316005]
[88]
Palm, W.; de Lange, T. How shelterin protects mammalian telomeres. Annu. Rev. Genet., 2008, 42(1), 301-334.
[http://dx.doi.org/10.1146/annurev.genet.41.110306.130350] [PMID: 18680434]
[89]
Herrmann, M.; Pusceddu, I.; März, W.; Herrmann, W. Telomere biology and age-related diseases. Clin. Chem. Lab. Med., 2018, 56(8), 1210-1222.
[http://dx.doi.org/10.1515/cclm-2017-0870] [PMID: 29494336]

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