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Expression of the Drosophila cancer-germline (CG), X-linked, head-to-head gene pair TrxT and dhd is normally germline-specific but becomes upregulated in brain tumours caused by mutation in l(3)mbt. Here, we show that TrxT and dhd play a major synergistic role in the emergence of l(3)mbt tumour-linked transcriptomic signatures and tumour development, which is remarkable, taking into account that these two genes are never expressed together under normal conditions. We also show that TrxT, but not dhd, is crucial for the growth of l(3)mbt allografts, hence suggesting that the initial stages of tumour development and long-term tumour growth may depend on different molecular pathways. In humans, head-to-head inverted gene pairs are abundant among CG genes that map to the X chromosome. Our results identify a first example of an X-linked, head-to-head CG gene pair in Drosophila, underpinning the potential of such CG genes, dispensable for normal development and homoeostasis of somatic tissue, as targets to curtail malignant growth with minimal impact on overall health.

Titel:	TrxT and dhd are dispensable for Drosophila brain development but essential for l(3)mbt brain tumour growth.
Autor/in / Beteiligte Person:	Molnar, C ; Heinen, JP ; Reina, J ; Llamazares, S ; Palumbo, E ; Pollarolo, G ; Gonzalez, C
Zeitschrift:	EMBO reports, 2024-05-15
Veröffentlichung:	Ahead of Print, 2024
Medientyp:	academicJournal
ISSN:	1469-3178 (electronic)
DOI:	10.1038/s44319-024-00154-1
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [EMBO Rep] 2024 May 15. <i>Date of Electronic Publication: </i>2024 May 15. References: AlOkda A, Van Raamsdonk JM (2023) Evolutionarily conserved role of thioredoxin systems in determining longevity. Antioxidants 12:944. (PMID: 10.3390/antiox120409443710731910135697) ; Arner ES, Holmgren A (2006) The thioredoxin system in cancer. Semin Cancer Biol 16:420–426. (PMID: 10.1016/j.semcancer.2006.10.00917092741) ; Barger CJ, Chee L, Albahrani M, Munoz-Trujillo C, Boghean L, Branick C, Odunsi K, Drapkin R, Zou L, Karpf AR (2021) Co-regulation and function of FOXM1/RHNO1 bidirectional genes in cancer. eLife 10:e55070. (PMID: 10.7554/eLife.55070338905748104967) ; Collet JF, Messens J (2010) Structure, function, and mechanism of thioredoxin proteins. Antioxid Redox Signal 13:1205–1216. (PMID: 10.1089/ars.2010.311420136512) ; Emelyanov AV, Fyodorov DV (2016) Thioredoxin-dependent disulfide bond reduction is required for protamine eviction from sperm chromatin. Genes Dev 30:2651–2656. (PMID: 10.1101/gad.290916.116280312475238724) ; Flores LC, Ortiz M, Dube S, Hubbard GB, Lee S, Salmon A, Zhang Y, Ikeno Y (2012) Thioredoxin, oxidative stress, cancer and aging. Longev Healthspan 1:4. (PMID: 10.1186/2046-2395-1-4247645103886257) ; Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R, Nicolay HJ, Sigalotti L, Maio M (2011) The biology of cancer testis antigens: putative function, regulation and therapeutic potential. Mol Oncol 5:164–182. (PMID: 10.1016/j.molonc.2011.02.001213766785528287) ; Freier R, Aragon E, Baginski B, Pluta R, Martin-Malpartida P, Ruiz L, Condeminas M, Gonzalez C, Macias MJ (2021) Structures of the germline-specific Deadhead and thioredoxin T proteins from Drosophila melanogaster reveal unique features among thioredoxins. IUCrJ 8:281–294. (PMID: 10.1107/S2052252521000221337084047924233) ; Gateff E, Loffler T, Wismar J (1993) A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene. Mech Dev 41:15–31. (PMID: 10.1016/0925-4773(93)90052-Y8507589) ; Gonzalez C, Glover DM (1993) Techniques for studying mitosis in Drosophila. In: Fantes P, Brooks R (eds) The cell cycle: a practical approach. Oxford University Press, p 143–176. ; Gramates LS, Agapite J, Attrill H, Calvi BR, Crosby MA, dos Santos G, Goodman JL, Goutte-Gattat D, Jenkins VK, Kaufman T et al (2022) FlyBase: a guided tour of highlighted features. Genetics 220:iyac035. (PMID: 10.1093/genetics/iyac035352665228982030) ; Hofmann O, Caballero OL, Stevenson BJ, Chen YT, Cohen T, Chua R, Maher CA, Panji S, Schaefer U, Kruger A et al (2008) Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci USA 105:20422–20427. (PMID: 10.1073/pnas.0810777105190881872603434) ; Holmgren A (1985) THIOREDOXIN. Annu Rev Biochem 54:237–271. (PMID: 10.1146/annurev.bi.54.070185.0013213896121) ; Hulsen T, de Vlieg J, Alkema W (2008) BioVenn—a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. BMC Genomics 9:488. (PMID: 10.1186/1471-2164-9-488189259492584113) ; Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C (2010) Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330:1824–1827. (PMID: 10.1126/science.119548121205669) ; Karlenius TC, Tonissen KF (2010) Thioredoxin and cancer: a role for thioredoxin in all states of tumor oxygenation. Cancers 2:209–232. (PMID: 10.3390/cancers2020209242810683835076) ; Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25:402–408. (PMID: 10.1006/meth.2001.126211846609) ; Molnar C, Heinen JP, Reina J, Llamazares S, Palumbo E, Breschi A, Gay M, Villarreal L, Vilaseca M, Pollarolo G et al (2019) The histone code reader PHD finger protein 7 controls sex-linked disparities in gene expression and malignancy in Drosophila. Sci Adv 5:eaaw7965. (PMID: 10.1126/sciadv.aaw7965314533296693905) ; Mondal S, Singh SP (2022) New insights on thioredoxins (Trxs) and glutaredoxins (Grxs) by in silico amino acid sequence, phylogenetic and comparative structural analyses in organisms of three domains of life. Heliyon 8:e10776. (PMID: 10.1016/j.heliyon.2022.e10776362038939529593) ; Nishinaka Y, Nakamura H, Masutani H, Yodoi J (2001) Redox control of cellular function by thioredoxin; a new therapeutic direction in host defence. Arch Immunol Ther Exp 49:285–292. ; Pellicena-Palle A, Stitzinger SM, Salz HK (1997) The function of the Drosophila thioredoxin homologue encoded by the deadhead gene is redox-dependent and blocks the initiation of development but not DNA synthesis. Mech Dev 62:61–65. (PMID: 10.1016/S0925-4773(96)00650-89106167) ; Petrova B, Liu K, Tian C, Kitaoka M, Freinkman E, Yang J, Orr-Weaver TL (2018) Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes. Proc Natl Acad Sci USA 115:E7978–E7986. (PMID: 10.1073/pnas.1807918115300824116112717) ; Powis G, Montfort WR (2001) Properties and biological activities of thioredoxins. Annu Rev Biophys Biomol Struct 30:421–455. (PMID: 10.1146/annurev.biophys.30.1.42111441809) ; Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP et al (2005) The DNA sequence of the human X chromosome. Nature 434:325–337. (PMID: 10.1038/nature03440157726512665286) ; Rossi F, Gonzalez C (2015) Studying tumor growth in Drosophila using the tissue allograft method. Nat Protoc 10:1525–1534. (PMID: 10.1038/nprot.2015.09626357008) ; Rossi F, Molnar C, Hashiyama K, Heinen JP, Pampalona J, Llamazares S, Reina J, Hashiyama T, Rai M, Pollarolo G et al (2017) An in vivo genetic screen in Drosophila identifies the orthologue of human cancer/testis gene SPO11 among a network of targets to inhibit lethal(3)malignant brain tumour growth. Open Biol 7:170156. (PMID: 10.1098/rsob.170156288553945577452) ; Salmaninejad A, Zamani MR, Pourvahedi M, Golchehre Z, Hosseini Bereshneh A, Rezaei N (2016) Cancer/testis antigens: expression, regulation, tumor invasion, and use in immunotherapy of cancers. Immunol Invest 45:619–640. (PMID: 10.1080/08820139.2016.119724127603913) ; Salz HK, Flickinger TW, Mittendorf E, Pellicena-Palle A, Petschek JP, Albrecht EB (1994) The Drosophila maternal effect locus deadhead encodes a thioredoxin homolog required for female meiosis and early embryonic development. Genetics 136:1075–1086. (PMID: 10.1093/genetics/136.3.107575163011205864) ; Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, Imamichi T, Chang W (2022) DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 50:W216–w221. (PMID: 10.1093/nar/gkac194353251859252805) ; Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer 5:615–625. (PMID: 10.1038/nrc166916034368) ; Stevenson BJ, Iseli C, Panji S, Zahn-Zabal M, Hide W, Old LJ, Simpson AJ, Jongeneel CV (2007) Rapid evolution of cancer/testis genes on the X chromosome. BMC Genomics 8:129. (PMID: 10.1186/1471-2164-8-129175214331890293) ; Svensson MJ, Chen JD, Pirrotta V, Larsson J (2003) The ThioredoxinT and deadhead gene pair encode testis- and ovary-specific thioredoxins in Drosophila melanogaster. Chromosoma 112:133–143. (PMID: 10.1007/s00412-003-0253-514579129) ; Svensson MJ, Larsson J (2007) Thioredoxin-2 affects lifespan and oxidative stress in Drosophila. Hereditas 144:25–32. (PMID: 10.1111/j.2007.0018-0661.01990.x17567437) ; Tirmarche S, Kimura S, Dubruille R, Horard B, Loppin B (2016) Unlocking sperm chromatin at fertilization requires a dedicated egg thioredoxin in Drosophila. Nat Commun 7:13539. (PMID: 10.1038/ncomms13539278768115122968) ; Torres-Campana D, Horard B, Denaud S, Benoit G, Loppin B, Orsi GA (2022) Three classes of epigenomic regulators converge to hyperactivate the essential maternal gene deadhead within a heterochromatin mini-domain. PLoS Genet 18:e1009615. (PMID: 10.1371/journal.pgen.1009615349827728759638) ; Warburton PE, Giordano J, Cheung F, Gelfand Y, Benson G (2004) Inverted repeat structure of the human genome: the X-chromosome contains a preponderance of large, highly homologous inverted repeats that contain testes genes. Genome Res 14:1861–1869. (PMID: 10.1101/gr.254290415466286524409) ; Wilkinson B, Gilbert HF (2004) Protein disulfide isomerase. Biochim Biophys Acta 1699:35–44. (PMID: 10.1016/S1570-9639(04)00063-915158710) ; Zhao Q, Caballero OL, Simpson AJ, Strausberg RL (2012) Differential evolution of MAGE genes based on expression pattern and selection pressure. PLoS ONE 7:e48240. (PMID: 10.1371/journal.pone.0048240231335773484994) Grant Information: PID2021-124716OB-I00 Ministerio de Ciencia e Innovación (MCIN) Contributed Indexing: Keywords: Cancer-Germline Genes; Cancer-Testis Genes; Malignant Growth; Tumours Entry Date(s): Date Created: 20240515 Latest Revision: 20240515 Update Code: 20240516

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TrxT and dhd are dispensable for Drosophila brain development but essential for l(3)mbt brain tumour growth.