APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression


Autoři: Hiroyuki Yamazaki aff001;  Kotaro Shirakawa aff001;  Tadahiko Matsumoto aff001;  Yasuhiro Kazuma aff001;  Hiroyuki Matsui aff001;  Yoshihito Horisawa aff001;  Emani Stanford aff001;  Anamaria Daniela Sarca aff001;  Ryutaro Shirakawa aff002;  Keisuke Shindo aff001;  Akifumi Takaori-Kondo aff001
Působiště autorů: Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan aff001;  Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan aff002
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0223463

Souhrn

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminase 3B (A3B) is a DNA editing enzyme which induces genomic DNA mutations in multiple myeloma and in various other cancers. APOBEC family proteins are highly homologous so it is especially difficult to investigate the biology of specifically A3B in cancer cells. To easily and comprehensively investigate A3B function in myeloma cells, we used CRISPR/Cas9 to generate A3B reporter cells that contain 3×FLAG tag and IRES-EGFP sequences integrated at the end of the A3B gene. These reporter cells stably express 3xFLAG tagged A3B and the reporter EGFP and this expression is enhanced by known stimuli, such as PMA. Conversely, shRNA knockdown of A3B decreased EGFP fluorescence and 3xFLAG tagged A3B protein levels. We screened a series of anticancer treatments using these cell lines and identified that most conventional therapies, such as antimetabolites or radiation, exacerbated endogenous A3B expression, but recent molecular targeted therapeutics, including bortezomib, lenalidomide and elotuzumab, did not. Furthermore, chemical inhibition of ATM, ATR and DNA-PK suppressed EGFP expression upon treatment with antimetabolites. These results suggest that DNA damage triggers A3B expression through ATM, ATR and DNA-PK signaling.

Klíčová slova:

Mutation – Cloning – Cancer treatment – Flow cytometry – Polymerase chain reaction – Plasmid construction – DNA damage – Myeloma cells


Zdroje

1. Henderson S, Fenton T. APOBEC3 genes: retroviral restriction factors to cancer drivers. Trends in molecular medicine. 2015;21(5):274–84. doi: 10.1016/j.molmed.2015.02.007 25820175

2. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. doi: 10.1038/nature12477 23945592

3. Swanton C, McGranahan N, Starrett GJ, Harris RS. APOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity. Cancer Discov. 2015;5(7):704–12. doi: 10.1158/2159-8290.CD-15-0344 26091828

4. Gao J, Choudhry H, Cao W. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like family genes activation and regulation during tumorigenesis. Cancer science. 2018;109(8):2375–82. doi: 10.1111/cas.13658 29856501

5. Walker BA, Wardell CP, Murison A, Boyle EM, Begum DB, Dahir NM, et al. APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma. Nat Commun. 2015;6:6997. doi: 10.1038/ncomms7997 25904160

6. Maura F, Petljak M, Lionetti M, Cifola I, Liang W, Pinatel E, et al. Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines. Leukemia. 2018;32(4):1044–8. doi: 10.1038/leu.2017.345 29209044

7. Yamazaki H, Shirakawa K, Matsumoto T, Hirabayashi S, Murakawa Y, Kobayashi M, et al. Endogenous APOBEC3B Overexpression Constitutively Generates DNA Substitutions and Deletions in Myeloma Cells. Scientific reports. 2019;9(1).

8. Sieuwerts AM, Willis S, Burns MB, Look MP, Meijer-Van Gelder ME, Schlicker A, et al. Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers. Hormones & cancer. 2014;5(6):405–13.

9. Law EK, Sieuwerts AM, LaPara K, Leonard B, Starrett GJ, Molan AM, et al. The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer. Science advances. 2016;2(10):e1601737. doi: 10.1126/sciadv.1601737 27730215

10. Yan S, He F, Gao B, Wu H, Li M, Huang L, et al. Increased APOBEC3B Predicts Worse Outcomes in Lung Cancer: A Comprehensive Retrospective Study. J Cancer. 2016;7(6):618–25. doi: 10.7150/jca.14030 27076842

11. Du Y, Tao X, Wu J, Yu H, Yu Y, Zhao H. APOBEC3B up-regulation independently predicts ovarian cancer prognosis: a cohort study. Cancer Cell Int. 2018;18:78. doi: 10.1186/s12935-018-0572-5 29853799

12. Ng JCF, Quist J, Grigoriadis A, Malim MH, Fraternali F. Pan-cancer transcriptomic analysis dissects immune and proliferative functions of APOBEC3 cytidine deaminases. Nucleic acids research. 2019.

13. Kanu N, Cerone MA, Goh G, Zalmas LP, Bartkova J, Dietzen M, et al. DNA replication stress mediates APOBEC3 family mutagenesis in breast cancer. Genome biology. 2016;17(1):185. doi: 10.1186/s13059-016-1042-9 27634334

14. Shimizu A, Fujimori H, Minakawa Y, Matsuno Y, Hyodo M, Murakami Y, et al. Onset of deaminase APOBEC3B induction in response to DNA double-strand breaks. Biochem Biophys Rep. 2018;16:115–21. doi: 10.1016/j.bbrep.2018.10.010 30417129

15. Vieira VC, Leonard B, White EA, Starrett GJ, Temiz NA, Lorenz LD, et al. Human papillomavirus E6 triggers upregulation of the antiviral and cancer genomic DNA deaminase APOBEC3B. mBio. 2014;5(6).

16. Mori S, Takeuchi T, Ishii Y, Kukimoto I. Identification of APOBEC3B promoter elements responsible for activation by human papillomavirus type 16 E6. Biochem Biophys Res Commun. 2015;460(3):555–60. doi: 10.1016/j.bbrc.2015.03.068 25800874

17. Leonard B, McCann JL, Starrett GJ, Kosyakovsky L, Luengas EM, Molan AM, et al. The PKC/NF-kappaB signaling pathway induces APOBEC3B expression in multiple human cancers. Cancer Res. 2015;75(21):4538–47. doi: 10.1158/0008-5472.CAN-15-2171-T 26420215

18. Maruyama W, Shirakawa K, Matsui H, Matsumoto T, Yamazaki H, Sarca AD, et al. Classical NF-kappaB pathway is responsible for APOBEC3B expression in cancer cells. Biochem Biophys Res Commun. 2016;478(3):1466–71. doi: 10.1016/j.bbrc.2016.08.148 27577680

19. Chou WC, Chen WT, Hsiung CN, Hu LY, Yu JC, Hsu HM, et al. B-Myb Induces APOBEC3B Expression Leading to Somatic Mutation in Multiple Cancers. Scientific reports. 2017;7:44089. doi: 10.1038/srep44089 28276478

20. Naito Y, Hino K, Bono H, Ui-Tei K. CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites. Bioinformatics (Oxford, England). 2015;31(7):1120–3.

21. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Nature protocols. 2013;8(11):2281–308. doi: 10.1038/nprot.2013.143 24157548

22. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelson T, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science (New York, NY). 2014;343(6166):84–7.

23. Guschin DY, Waite AJ, Katibah GE, Miller JC, Holmes MC, Rebar EJ. A rapid and general assay for monitoring endogenous gene modification. Methods in molecular biology (Clifton, NJ). 2010;649:247–56.

24. Blum R, Pfeiffer F, Feick P, Nastainczyk W, Kohler B, Schafer KH, et al. Intracellular localization and in vivo trafficking of p24A and p23. Journal of cell science. 1999;112 (Pt 4):537–48.

25. Salomonis N, Schlieve CR, Pereira L, Wahlquist C, Colas A, Zambon AC, et al. Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc Natl Acad Sci U S A. 2010;107(23):10514–9. doi: 10.1073/pnas.0912260107 20498046

26. Burns MB, Lackey L, Carpenter MA, Rathore A, Land AM, Leonard B, et al. APOBEC3B is an enzymatic source of mutation in breast cancer. Nature. 2013;494(7437):366–70. doi: 10.1038/nature11881 23389445

27. Hellman NE, Spector J, Robinson J, Zuo X, Saunier S, Antignac C, et al. Matrix metalloproteinase 13 (MMP13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), regulated by the MAPK pathway, are both necessary for Madin-Darby canine kidney tubulogenesis. The Journal of biological chemistry. 2008;283(7):4272–82. doi: 10.1074/jbc.M708027200 18039671

28. Eggenschwiler R, Loya K, Wu G, Sharma AD, Sgodda M, Zychlinski D, et al. Sustained knockdown of a disease-causing gene in patient-specific induced pluripotent stem cells using lentiviral vector-based gene therapy. Stem cells translational medicine. 2013;2(9):641–54. doi: 10.5966/sctm.2013-0017 23926210

29. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone marrow transplantation. 2013;48(3):452–8. doi: 10.1038/bmt.2012.244 23208313

30. Li M, Yu X. The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy. Oncogene. 2015;34(26):3349–56. doi: 10.1038/onc.2014.295 25220415

31. Blackford AN, Jackson SP. ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response. Molecular cell. 2017;66(6):801–17. doi: 10.1016/j.molcel.2017.05.015 28622525

32. Won J, Kim M, Kim N, Ahn JH, Lee WG, Kim SS, et al. Small molecule-based reversible reprogramming of cellular lifespan. Nature chemical biology. 2006;2(7):369–74. doi: 10.1038/nchembio800 16767085

33. Cho YS, Kim BS, Sim CK, Kim I, Lee MS. Establishment of IL-7 Expression Reporter Human Cell Lines, and Their Feasibility for High-Throughput Screening of IL-7-Upregulating Chemicals. PLoS One. 2016;11(9):e0161899. doi: 10.1371/journal.pone.0161899 27589392

34. Shan L, Wang D, Mao Q, Xia H. Establishment of a DGKtheta Endogenous Promoter Luciferase Reporter HepG2 Cell Line for Studying the Transcriptional Regulation of DGKtheta Gene. Applied biochemistry and biotechnology. 2019;187(4):1344–55. doi: 10.1007/s12010-018-2890-4 30229432

35. Li Z, Zhao J, Muhammad N, Wang D, Mao Q, Xia H. Establishment of a HEK293 cell line by CRISPR/Cas9-mediated luciferase knock-in to study transcriptional regulation of the human SREBP1 gene. Biotechnology letters. 2018;40(11–12):1495–506. doi: 10.1007/s10529-018-2608-2 30232659

36. Veach RA, Wilson MH. CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line. PLoS One. 2018;13(9):e0204487. doi: 10.1371/journal.pone.0204487 30260998

37. Li Y, Li S, Li Y, Xia H, Mao Q. Generation of a novel HEK293 luciferase reporter cell line by CRISPR/Cas9-mediated site-specific integration in the genome to explore the transcriptional regulation of the PGRN gene. Bioengineered. 2019;10(1):98–107. doi: 10.1080/21655979.2019.1607126 31023186

38. Shinohara M, Io K, Shindo K, Matsui M, Sakamoto T, Tada K, et al. APOBEC3B can impair genomic stability by inducing base substitutions in genomic DNA in human cells. Scientific reports. 2012;2:806. doi: 10.1038/srep00806 23150777

39. Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA, Raine K, Campbell PJ, et al. DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis. Elife. 2013;2:e00534. doi: 10.7554/eLife.00534 23599896

40. Akre MK, Starrett GJ, Quist JS, Temiz NA, Carpenter MA, Tutt AN, et al. Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B. PLoS One. 2016;11(5):e0155391. doi: 10.1371/journal.pone.0155391 27163364

41. Hoopes JI, Cortez LM, Mertz TM, Malc EP, Mieczkowski PA, Roberts SA. APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication. Cell Rep. 2016;14(6):1273–82. doi: 10.1016/j.celrep.2016.01.021 26832400

42. Zhang W, Zhang X, Tian C, Wang T, Sarkis PT, Fang Y, et al. Cytidine deaminase APOBEC3B interacts with heterogeneous nuclear ribonucleoprotein K and suppresses hepatitis B virus expression. Cellular microbiology. 2008;10(1):112–21. doi: 10.1111/j.1462-5822.2007.01020.x 17672864

43. Xiao X, Yang H, Arutiunian V, Fang Y, Besse G, Morimoto C, et al. Structural determinants of APOBEC3B non-catalytic domain for molecular assembly and catalytic regulation. Nucleic acids research. 2017;45(12):7494–506. doi: 10.1093/nar/gkx362 28575276

44. Mishra N, Reddy KS, Timilsina U, Gaur D, Gaur R. Human APOBEC3B interacts with the heterogenous nuclear ribonucleoprotein A3 in cancer cells. Journal of cellular biochemistry. 2018;119(8):6695–703. doi: 10.1002/jcb.26855 29693745

45. Vesela E, Chroma K, Turi Z, Mistrik M. Common Chemical Inductors of Replication Stress: Focus on Cell-Based Studies. Biomolecules. 2017;7(1).

46. Krakoff IH, Brown NC, Reichard P. Inhibition of ribonucleoside diphosphate reductase by hydroxyurea. Cancer Res. 1968;28(8):1559–65. 4876978

47. Cheng CH, Kuchta RD. DNA polymerase epsilon: aphidicolin inhibition and the relationship between polymerase and exonuclease activity. Biochemistry. 1993;32(33):8568–74. doi: 10.1021/bi00084a025 8395209

48. Saintigny Y, Delacote F, Vares G, Petitot F, Lambert S, Averbeck D, et al. Characterization of homologous recombination induced by replication inhibition in mammalian cells. The EMBO journal. 2001;20(14):3861–70. doi: 10.1093/emboj/20.14.3861 11447127

49. Ewald B, Sampath D, Plunkett W. H2AX phosphorylation marks gemcitabine-induced stalled replication forks and their collapse upon S-phase checkpoint abrogation. Molecular cancer therapeutics. 2007;6(4):1239–48. doi: 10.1158/1535-7163.MCT-06-0633 17406032

50. Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB Jr., Stewart L. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A. 2002;99(24):15387–92. doi: 10.1073/pnas.242259599 12426403

51. Tuduri S, Crabbe L, Conti C, Tourriere H, Holtgreve-Grez H, Jauch A, et al. Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nature cell biology. 2009;11(11):1315–24. doi: 10.1038/ncb1984 19838172

52. Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nature reviews Cancer. 2009;9(5):338–50. doi: 10.1038/nrc2607 19377506

53. Dronkert ML, Kanaar R. Repair of DNA interstrand cross-links. Mutation research. 2001;486(4):217–47. doi: 10.1016/s0921-8777(01)00092-1 11516927

54. Koberle B, Masters JR, Hartley JA, Wood RD. Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. Current biology: CB. 1999;9(5):273–6. doi: 10.1016/s0960-9822(99)80118-3 10074455

55. Damsma GE, Alt A, Brueckner F, Carell T, Cramer P. Mechanism of transcriptional stalling at cisplatin-damaged DNA. Nat Struct Mol Biol. 2007;14(12):1127–33. doi: 10.1038/nsmb1314 17994106

56. Borst P, Rottenberg S, Jonkers J. How do real tumors become resistant to cisplatin? Cell cycle (Georgetown, Tex). 2008;7(10):1353–9.

57. Sedletska Y, Fourrier L, Malinge JM. Modulation of MutS ATP-dependent functional activities by DNA containing a cisplatin compound lesion (base damage and mismatch). Journal of molecular biology. 2007;369(1):27–40. doi: 10.1016/j.jmb.2007.02.048 17400248

58. Brown R, Clugston C, Burns P, Edlin A, Vasey P, Vojtesek B, et al. Increased accumulation of p53 protein in cisplatin-resistant ovarian cell lines. International journal of cancer. 1993;55(4):678–84. doi: 10.1002/ijc.2910550428 8406999

59. Hayashi MT, Cesare AJ, Fitzpatrick JA, Lazzerini-Denchi E, Karlseder J. A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nat Struct Mol Biol. 2012;19(4):387–94. doi: 10.1038/nsmb.2245 22407014

60. Li H, Chang TW, Tsai YC, Chu SF, Wu YY, Tzang BS, et al. Colcemid inhibits the rejoining of the nucleotide excision repair of UVC-induced DNA damages in Chinese hamster ovary cells. Mutation research. 2005;588(2):118–28. doi: 10.1016/j.mrgentox.2005.09.005 16290038

61. Wakasugi M, Sasaki T, Matsumoto M, Nagaoka M, Inoue K, Inobe M, et al. Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells. The Journal of biological chemistry. 2014;289(41):28730–7. doi: 10.1074/jbc.M114.589747 25164823

62. Stiff T, Walker SA, Cerosaletti K, Goodarzi AA, Petermann E, Concannon P, et al. ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. The EMBO journal. 2006;25(24):5775–82. doi: 10.1038/sj.emboj.7601446 17124492

63. Choi S, Toledo LI, Fernandez-Capetillo O, Bakkenist CJ. CGK733 does not inhibit ATM or ATR kinase activity in H460 human lung cancer cells. DNA repair. 2011;10(10):1000–1; author reply 2. doi: 10.1016/j.dnarep.2011.07.013 21865098

64. Williams TM, Nyati S, Ross BD, Rehemtulla A. Molecular imaging of the ATM kinase activity. Int J Radiat Oncol Biol Phys. 2013;86(5):969–77. doi: 10.1016/j.ijrobp.2013.04.028 23726004

65. Fallone F, Britton S, Nieto L, Salles B, Muller C. ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression. Oncogene. 2013;32(37):4387–96. doi: 10.1038/onc.2012.462 23085754

66. Bhattacharya S, Ray RM, Johnson LR. Role of polyamines in p53-dependent apoptosis of intestinal epithelial cells. Cellular signalling. 2009;21(4):509–22. doi: 10.1016/j.cellsig.2008.12.003 19136059

67. Suzuki T, Tsuzuku J, Hayashi A, Shiomi Y, Iwanari H, Mochizuki Y, et al. Inhibition of DNA damage-induced apoptosis through Cdc7-mediated stabilization of Tob. The Journal of biological chemistry. 2012;287(48):40256–65. doi: 10.1074/jbc.M112.353805 23066029

68. Sakasai R, Teraoka H, Tibbetts RS. Proteasome inhibition suppresses DNA-dependent protein kinase activation caused by camptothecin. DNA repair. 2010;9(1):76–82. doi: 10.1016/j.dnarep.2009.10.008 19959400

69. Jacquemont C, Taniguchi T. Proteasome function is required for DNA damage response and fanconi anemia pathway activation. Cancer Res. 2007;67(15):7395–405. doi: 10.1158/0008-5472.CAN-07-1015 17671210


Článok vyšiel v časopise

PLOS One


2020 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa