The Biological Significance of AFF4: Promoting Transcription Elongation, Osteogenic Differentiation and Tumor Progression


Дәйексөз келтіру

Толық мәтін

Аннотация

As a member of the AF4/FMR2 (AFF) family, AFF4 is a scaffold protein in the superelongation complex (SEC). In this mini-view, we discuss the role of AFF4 as a transcription elongation factor that mediates HIV activation and replication and stem cell osteogenic differentiation. AFF4 also promotes the progression of head and neck squamous cell carcinoma, leukemia, breast cancer, bladder cancer and other malignant tumors. The biological function of AFF4 is largely achieved through SEC assembly, regulates SRY-box transcription factor 2 (SOX2), MYC, estrogen receptor alpha (ESR1), inhibitor of differentiation 1 (ID1), c-Jun and noncanonical nuclear factor-κB (NF-κB) transcription and combines with fusion in sarcoma (FUS), unique regulatory cyclins (CycT1), or mixed lineage leukemia (MLL). We explore the prospects of using AFF4 as a therapeutic in Acquired immunodeficiency syndrome (AIDS) and malignant tumors and its potential as a stemness regulator.

Авторлар туралы

Qian Long

Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University,

Email: info@benthamscience.net

Mingli Xiang

Department of Orthodontics II,, Affiliated Stomatological Hospital of Zunyi Medical University

Email: info@benthamscience.net

Linlin Xiao

Department of Orthodontics II, Affiliated Stomatological Hospital of Zunyi Medical University

Email: info@benthamscience.net

Jiajia Wang

Department of Orthodontics II,, Affiliated Stomatological Hospital of Zunyi Medical University

Email: info@benthamscience.net

Xiaoyan Guan

Department of Orthodontics II,, Affiliated Stomatological Hospital of Zunyi Medical University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Jianguo Liu

Department of Orthodontics II,, Affiliated Stomatological Hospital of Zunyi Medical University,

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Chengcheng Liao

Department of Orthodontics II,, Affiliated Stomatological Hospital of Zunyi Medical University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Әдебиет тізімі

  1. Luo, Z.; Lin, C.; Guest, E.; Garrett, A.S.; Mohaghegh, N.; Swanson, S.; Marshall, S.; Florens, L.; Washburn, M.P.; Shilatifard, A. The super elongation complex family of RNA polymerase II elongation factors: Gene target specificity and transcriptional output. Mol. Cell. Biol., 2012, 32(13), 2608-2617. doi: 10.1128/MCB.00182-12 PMID: 22547686
  2. Lu, H.; Li, Z.; Zhang, W.; Schulze-Gahmen, U.; Xue, Y.; Zhou, Q. Gene target specificity of the Super Elongation Complex (SEC) family: How HIV-1 Tat employs selected SEC members to activate viral transcription. Nucleic Acids Res., 2015, 43(12), 5868-5879. doi: 10.1093/nar/gkv541 PMID: 26007649
  3. Bitoun, E.; Davies, K.E. The robotic mouse: Unravelling the function of AF4 in the cerebellum. Cerebellum, 2005, 4(4), 250-260. doi: 10.1080/14734220500325897 PMID: 16321881
  4. Taki, T.; Kano, H.; Taniwaki, M.; Sako, M.; Yanagisawa, M.; Hayashi, Y. AF5q31, a newly identified AF4 -related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23). Proc. Natl. Acad. Sci. USA, 1999, 96(25), 14535-14540. doi: 10.1073/pnas.96.25.14535 PMID: 10588740
  5. Estable, M.C.; Naghavi, M.H.; Kato, H.; Xiao, H.; Qin, J.; Vahlne, A.; Roeder, R.G. MCEF, the newest member of the AF4 family of transcription factors involved in leukemia, is a positive transcription elongation factor-b-associated protein. J. Biomed. Sci., 2002, 9(3), 234-245. doi: 10.1007/BF02256070 PMID: 12065898
  6. Deveney, R.; Chervinsky, D.S.; Jani-Sait, S.N.; Grossi, M. Insertion of MLL sequences into chromosome band 5q31 results in an MLL-AF5Q31 fusion and is a rare but recurrent abnormality associated with infant leukemia. Genes Chromosomes Cancer, 2003, 3, 326-331. doi: 10.1002/gcc.10224
  7. Mueller, D.; Bach, C.; Zeisig, D.; Garcia-Cuellar, M.P.; Monroe, S.; Sreekumar, A.; Zhou, R.; Nesvizhskii, A.; Chinnaiyan, A.; Hess, J.L.; Slany, R.K. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood, 2007, 110(13), 4445-4454. doi: 10.1182/blood-2007-05-090514 PMID: 17855633
  8. Bitoun, E.; Oliver, P.L.; Davies, K.E. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum. Mol. Genet., 2007, 16(1), 92-106. doi: 10.1093/hmg/ddl444 PMID: 17135274
  9. Benedikt, A.; Baltruschat, S.; Scholz, B.; Bursen, A.; Arrey, T.N.; Meyer, B.; Varagnolo, L.; Müller, A.M.; Karas, M.; Dingermann, T.; Marschalek, R. The leukemogenic AF4–MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia, 2011, 25(1), 135-144. doi: 10.1038/leu.2010.249 PMID: 21030982
  10. Schulze-Gahmen, U.; Upton, H.; Birnberg, A.; Bao, K.; Chou, S.; Krogan, N.J.; Zhou, Q.; Alber, T. The AFF4 scaffold binds human P-TEFb adjacent to HIV Tat. eLife, 2013, 2, e00327. doi: 10.7554/eLife.00327 PMID: 23471103
  11. Schulze-Gahmen, U.; Lu, H.; Zhou, Q.; Alber, T. AFF4 binding to Tat-P-TEFb indirectly stimulates TAR recognition of super elongation complexes at the HIV promoter. eLife, 2014, 3, e02375. doi: 10.7554/eLife.02375 PMID: 24843025
  12. Schulze-Gahmen, U.; Echeverria, I.; Stjepanovic, G.; Bai, Y.; Lu, H.; Schneidman-Duhovny, D.; Doudna, J.A.; Zhou, Q.; Sali, A.; Hurley, J.H. Insights into HIV-1 proviral transcription from integrative structure and dynamics of the Tat:AFF4:P-TEFb:TAR complex. eLife, 2016, 5, e15910. doi: 10.7554/eLife.15910 PMID: 27731797
  13. Schulze-Gahmen, U.; Hurley, J.H. Structural mechanism for HIV-1 TAR loop recognition by Tat and the super elongation complex. Proc. Natl. Acad. Sci. USA, 2018, 115(51), 12973-12978. doi: 10.1073/pnas.1806438115 PMID: 30514815
  14. Qi, S.; Li, Z.; Schulze-Gahmen, U.; Stjepanovic, G.; Zhou, Q.; Hurley, J.H. Structural basis for ELL2 and AFF4 activation of HIV-1 proviral transcription. Nat. Commun., 2017, 8(1), 14076. doi: 10.1038/ncomms14076 PMID: 28134250
  15. Leach, B.I.; Kuntimaddi, A.; Schmidt, C.R.; Cierpicki, T.; Johnson, S.A.; Bushweller, J.H. Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding. Structure, 2013, 21(1), 176-183. doi: 10.1016/j.str.2012.11.011 PMID: 23260655
  16. Yokoyama, A.; Lin, M.; Naresh, A.; Kitabayashi, I.; Cleary, M.L. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell, 2010, 17(2), 198-212. doi: 10.1016/j.ccr.2009.12.040 PMID: 20153263
  17. Kuzmina, A.; Krasnopolsky, S.; Taube, R. Super elongation complex promotes early HIV transcription and its function is modulated by P-TEFb. Transcription, 2017, 8(3), 133-149. doi: 10.1080/21541264.2017.1295831 PMID: 28340332
  18. Chen, Y.; Cramer, P. Structure of the super-elongation complex subunit AFF4 C-terminal homology domain reveals requirements for AFF homo- and heterodimerization. J. Biol. Chem., 2019, 294(27), 10663-10673. doi: 10.1074/jbc.RA119.008577 PMID: 31147444
  19. Urano, A.; Endoh, M.; Wada, T.; Morikawa, Y.; Itoh, M.; Kataoka, Y.; Taki, T.; Akazawa, H.; Nakajima, H.; Komuro, I.; Yoshida, N.; Hayashi, Y.; Handa, H.; Kitamura, T.; Nosaka, T. Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia. Mol. Cell. Biol., 2005, 25(15), 6834-6845. doi: 10.1128/MCB.25.15.6834-6845.2005 PMID: 16024815
  20. Raible, S.E.; Mehta, D.; Bettale, C.; Fiordaliso, S.; Kaur, M.; Medne, L.; Rio, M.; Haan, E.; White, S.M.; Cusmano-Ozog, K.; Nishi, E.; Guo, Y.; Wu, H.; Shi, X.; Zhao, Q.; Zhang, X.; Lei, Q.; Lu, A.; He, X.; Okamoto, N.; Miyake, N.; Piccione, J.; Allen, J.; Matsumoto, N.; Pipan, M.; Krantz, I.D.; Izumi, K. Clinical and molecular spectrum of CHOPS syndrome. Am. J. Med. Genet. A., 2019, 179(7), ajmg.a.61174. doi: 10.1002/ajmg.a.61174 PMID: 31058441
  21. Kim, S.Y.; Kim, M.J.; Kim, S.J.; Lee, J.E.; Chae, J.H.; Ko, J.M. A case of CHOPS syndrome accompanied with moyamoya disease and systemic vasculopathy. Brain Dev., 2021, 43(3), 454-458. doi: 10.1016/j.braindev.2020.11.004 PMID: 33248856
  22. Li, J.; Lee, Y.K.; Fu, W.; Whalen, A.M.; Estable, M.C.; Raftery, L.A.; White, K.; Weiner, L.; Brissette, J.L. Modeling by disruption and a selected‐for partner for the nude locus. EMBO Rep., 2021, 22(3), e49804. doi: 10.15252/embr.201949804 PMID: 33369874
  23. Mu, J.; Xu, Y.; Zhu, H. AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis. Nan Fang Yi Ke Da Xue Xue Bao, 2023, 43(5), 741-748. doi: 10.12122/j.issn.1673-4254.2023.05.09 PMID: 37313815
  24. Archin, N.M.; Sung, J.M.; Garrido, C.; Soriano-Sarabia, N.; Margolis, D.M. Eradicating HIV-1 infection: Seeking to clear a persistent pathogen. Nat. Rev. Microbiol., 2014, 12(11), 750-764. doi: 10.1038/nrmicro3352 PMID: 25402363
  25. Margolis, D.M.; Garcia, J.V.; Hazuda, D.J.; Haynes, B.F. Latency reversal and viral clearance to cure HIV-1. Science, 2016, 353(6297), aaf6517. doi: 10.1126/science.aaf6517 PMID: 27463679
  26. Abner, E.; Jordan, A. HIV "shock and kill" therapy: In need of revision. Antiviral Res., 2019, 166, 19-34. doi: 10.1016/j.antiviral.2019.03.008 PMID: 30914265
  27. Vansant, G.; Bruggemans, A.; Janssens, J.; Debyser, Z. Block-and-lock strategies to cure HIV infection. Viruses, 2020, 12(1), 84. doi: 10.3390/v12010084 PMID: 31936859
  28. Jonkers, I.; Lis, J.T. Getting up to speed with transcription elongation by RNA polymerase II. Nat. Rev. Mol. Cell Biol., 2015, 16(3), 167-177. doi: 10.1038/nrm3953 PMID: 25693130
  29. Zhou, Q.; Li, T.; Price, D.H. RNA polymerase II elongation control. Annu. Rev. Biochem., 2012, 81(1), 119-143. doi: 10.1146/annurev-biochem-052610-095910 PMID: 22404626
  30. Etchegaray, J.P.; Zhong, L.; Li, C.; Henriques, T.; Ablondi, E.; Nakadai, T.; Van Rechem, C.; Ferrer, C.; Ross, K.N.; Choi, J.E.; Samarakkody, A.; Ji, F.; Chang, A.; Sadreyev, R.I.; Ramaswamy, S.; Nechaev, S.; Whetstine, J.R.; Roeder, R.G.; Adelman, K.; Goren, A.; Mostoslavsky, R. The histone deacetylase SIRT6 restrains transcription elongation via promoter-proximal pausing. Mol. Cell, 2019, 75(4), 683-699.e7. doi: 10.1016/j.molcel.2019.06.034 PMID: 31399344
  31. He, N.; Liu, M.; Hsu, J.; Xue, Y.; Chou, S.; Burlingame, A.; Krogan, N.J.; Alber, T.; Zhou, Q. HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription. Mol. Cell, 2010, 38(3), 428-438. doi: 10.1016/j.molcel.2010.04.013 PMID: 20471948
  32. Peterlin, B.M.; Price, D.H. Controlling the elongation phase of transcription with P-TEFb. Mol. Cell, 2006, 23(3), 297-305. doi: 10.1016/j.molcel.2006.06.014 PMID: 16885020
  33. Gu, J.; Babayeva, N.D.; Suwa, Y.; Baranovskiy, A.G.; Price, D.H.; Tahirov, T.H. Crystal structure of HIV-1 Tat complexed with human P-TEFb and AFF4. Cell Cycle, 2014, 13(11), 1788-1797. doi: 10.4161/cc.28756 PMID: 24727379
  34. Chou, S.; Upton, H.; Bao, K.; Schulze-Gahmen, U.; Samelson, A.J.; He, N.; Nowak, A.; Lu, H.; Krogan, N.J.; Zhou, Q.; Alber, T. HIV-1 Tat recruits transcription elongation factors dispersed along a flexible AFF4 scaffold. Proc. Natl. Acad. Sci. USA, 2013, 110(2), E123-E131. doi: 10.1073/pnas.1216971110 PMID: 23251033
  35. Li, Z.; Lu, H.; Zhou, Q. A minor subset of super elongation complexes plays a predominant role in reversing HIV-1 Latency. Mol. Cell. Biol., 2016, 36(7), 1194-1205. doi: 10.1128/MCB.00994-15 PMID: 26830226
  36. Tang, D.; Chen, C.; Liao, G.; Liu, J.; Liao, B.; Huang, Q.; Chen, Q.; Zhao, J.; Jiang, H.; Duan, J.; Huang, J.; Wang, K.; Wang, J.; Zhou, C.; Chu, W.; Li, W.; Sun, B.; Li, Z.; Dai, L.; Fu, X.; Cheng, W.; Xue, Y.; Qi, S. Structural and functional insight into the effect of AFF4 dimerization on activation of HIV-1 proviral transcription. Cell Discov., 2020, 6(1), 7. doi: 10.1038/s41421-020-0142-6 PMID: 32128251
  37. Sévigny, M.; Bourdeau Julien, I.; Venkatasubramani, J.P.; Hui, J.B.; Dutchak, P.A.; Sephton, C.F. FUS contributes to mTOR-dependent inhibition of translation. J. Biol. Chem., 2020, 295(52), 18459-18473. doi: 10.1074/jbc.RA120.013801 PMID: 33082139
  38. Tan, A.Y.; Manley, J.L. TLS inhibits RNA polymerase III transcription. Mol. Cell. Biol., 2010, 30(1), 186-196. doi: 10.1128/MCB.00884-09 PMID: 19841068
  39. Yu, Y.; Reed, R. FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP. Proc. Natl. Acad. Sci. USA, 2015, 112(28), 8608-8613. doi: 10.1073/pnas.1506282112 PMID: 26124092
  40. Krasnopolsky, S.; Marom, L.; Victor, R.A.; Kuzmina, A.; Schwartz, J.C.; Fujinaga, K.; Taube, R. Fused in sarcoma silences HIV gene transcription and maintains viral latency through suppressing AFF4 gene activation. Retrovirology, 2019, 16(1), 16. doi: 10.1186/s12977-019-0478-x PMID: 31238957
  41. Loughlin, F.E.; Lukavsky, P.J.; Kazeeva, T.; Reber, S.; Hock, E.M.; Colombo, M.; Von Schroetter, C.; Pauli, P.; Cléry, A.; Mühlemann, O.; Polymenidou, M.; Ruepp, M.D.; Allain, F.H.T. The solution structure of FUS Bound to RNA reveals a bipartite mode of RNA recognition with both sequence and shape specificity. Mol. Cell, 2019, 73(3), 490-504.e6. doi: 10.1016/j.molcel.2018.11.012 PMID: 30581145
  42. Uccelli, A.; Moretta, L.; Pistoia, V. Mesenchymal stem cells in health and disease. Nat. Rev. Immunol., 2008, 8(9), 726-736. doi: 10.1038/nri2395 PMID: 19172693
  43. Raggatt, L.J.; Partridge, N.C. Cellular and molecular mechanisms of bone remodeling. J. Biol. Chem., 2010, 285(33), 25103-25108. doi: 10.1074/jbc.R109.041087 PMID: 20501658
  44. Frith, J.; Genever, P. Transcriptional control of mesenchymal stem cell differentiation. Transfus. Med. Hemother., 2008, 35(3), 216-227. doi: 10.1159/000127448 PMID: 21547119
  45. Yuan, Q.; Jiang, Y.; Zhao, X.; Sato, T.; Densmore, M.; Schüler, C.; Erben, R.G.; McKee, M.D.; Lanske, B. Increased osteopontin contributes to inhibition of bone mineralization in FGF23-deficient mice. J. Bone Miner. Res., 2014, 29(3), 693-704. doi: 10.1002/jbmr.2079 PMID: 24038141
  46. Yuan, Q.; Sato, T.; Densmore, M.; Saito, H.; Schüler, C.; Erben, R.G.; Lanske, B. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice. PLoS Genet., 2012, 8(5), e1002726. doi: 10.1371/journal.pgen.1002726 PMID: 22615584
  47. Rahman, M.S.; Akhtar, N.; Jamil, H.M.; Banik, R.S.; Asaduzzaman, S.M. TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation. Bone Res., 2015, 3(1), 15005. doi: 10.1038/boneres.2015.5 PMID: 26273537
  48. Wu, M.; Chen, G.; Li, Y.P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res., 2016, 4(1), 16009. doi: 10.1038/boneres.2016.9 PMID: 27563484
  49. Guo, J.; Liu, M.; Yang, D.; Bouxsein, M.L.; Saito, H.; Galvin, R.J.S.; Kuhstoss, S.A.; Thomas, C.C.; Schipani, E.; Baron, R.; Bringhurst, F.R.; Kronenberg, H.M. Suppression of Wnt signaling by Dkk1 attenuates PTH-mediated stromal cell response and new bone formation. Cell Metab., 2010, 11(2), 161-171. doi: 10.1016/j.cmet.2009.12.007 PMID: 20142103
  50. Zhou, C.; Xiong, Q.; Zhu, X.; Du, W.; Deng, P.; Li, X.; Jiang, Y.; Zou, S.; Wang, C.; Yuan, Q. AFF1 and AFF4 differentially regulate the osteogenic differentiation of human MSCs. Bone Res., 2017, 5(1), 17044. doi: 10.1038/boneres.2017.44 PMID: 28955517
  51. Lambrichts, I.; Driesen, R.B.; Dillen, Y.; Gervois, P.; Ratajczak, J.; Vangansewinkel, T.; Wolfs, E.; Bronckaers, A.; Hilkens, P. Dental pulp stem cells: Their potential in reinnervation and angiogenesis by using scaffolds. J. Endod., 2017, 43(9), S12-S16. doi: 10.1016/j.joen.2017.06.001 PMID: 28781091
  52. Nuti, N.; Corallo, C.; Chan, B.M.F.; Ferrari, M.; Gerami-Naini, B. Multipotent differentiation of human dental pulp stem cells: A literature review. Stem Cell Rev., 2016, 12(5), 511-523. doi: 10.1007/s12015-016-9661-9 PMID: 27240827
  53. Zhang, Y.; Xiao, Q.; Wu, Z.; Xu, R.; Zou, S.; Zhou, C. AFF4 enhances odontogenic differentiation of human dental pulp cells. Biochem. Biophys. Res. Commun., 2020, 525(3), 687-692. doi: 10.1016/j.bbrc.2020.02.122 PMID: 32139123
  54. Lee, D.S.; Roh, S.Y.; Park, J.C. The Nfic-osterix pathway regulates ameloblast differentiation and enamel formation. Cell Tissue Res., 2018, 374(3), 531-540. doi: 10.1007/s00441-018-2901-3 PMID: 30091046
  55. Wang, J.; Feng, J.Q. Signaling pathways critical for tooth root formation. J. Dent. Res., 2017, 96(11), 1221-1228. doi: 10.1177/0022034517717478 PMID: 28665752
  56. Xiao, Q.; Zhang, Y.; Qi, X.; Chen, Y.; Sheng, R.; Xu, R.; Yuan, Q.; Zhou, C. AFF4 regulates osteogenic differentiation of human dental follicle cells. Int. J. Oral Sci., 2020, 12(1), 20. doi: 10.1038/s41368-020-0083-9 PMID: 32606293
  57. Kristensen, L.S.; Andersen, M.S.; Stagsted, L.V.W.; Ebbesen, K.K.; Hansen, T.B.; Kjems, J. The biogenesis, biology and characterization of circular RNAs. Nat. Rev. Genet., 2019, 20(11), 675-691. doi: 10.1038/s41576-019-0158-7 PMID: 31395983
  58. Liu, C.; Liu, A.S.; Zhong, D.; Wang, C.G.; Yu, M.; Zhang, H.W.; Xiao, H.; Liu, J.H.; Zhang, J.; Yin, K. Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis. Cell Death Dis., 2021, 12(7), 631. doi: 10.1038/s41419-021-03877-4 PMID: 34145212
  59. Mi, B.; Xiong, Y.; Chen, L.; Yan, C.; Endo, Y.; Liu, Y.; Liu, J.; Hu, L.; Hu, Y.; Sun, Y.; Cao, F.; Zhou, W.; Liu, G. CircRNA AFF4 promotes osteoblast cells proliferation and inhibits apoptosis via the Mir-7223-5p/PIK3R1 axis. Aging, 2019, 11(24), 11988-12001. doi: 10.18632/aging.102524 PMID: 31848327
  60. Novak, D.; Hüser, L.; Elton, J.J.; Umansky, V.; Altevogt, P.; Utikal, J. SOX2 in development and cancer biology. Semin. Cancer Biol., 2020, 67(Pt 1), 74-82. doi: 10.1016/j.semcancer.2019.08.007 PMID: 31412296
  61. Deng, P.; Wang, J.; Zhang, X.; Wu, X.; Ji, N.; Li, J.; Zhou, M.; Jiang, L.; Zeng, X.; Chen, Q. AFF4 promotes tumorigenesis and tumor-initiation capacity of head and neck squamous cell carcinoma cells by regulating SOX2. Carcinogenesis, 2018, 39(7), 937-947. doi: 10.1093/carcin/bgy046 PMID: 29741610
  62. Chen, X.Y.; Zhang, J.; Zhu, J.S. The role of m6A RNA methylation in human cancer. Mol. Cancer, 2019, 18(1), 103. doi: 10.1186/s12943-019-1033-z PMID: 31142332
  63. Gao, Q.; Zheng, J.; Ni, Z.; Sun, P.; Yang, C.; Cheng, M.; Wu, M.; Zhang, X.; Yuan, L.; Zhang, Y.; Li, Y. The m 6 A methylation-regulated AFF4 promotes Self-Renewal of bladder cancer stem cells. Stem Cells Int., 2020, 2020, 1-12. doi: 10.1155/2020/8849218 PMID: 32676121
  64. Cheng, M.; Sheng, L.; Gao, Q.; Xiong, Q.; Zhang, H.; Wu, M.; Liang, Y.; Zhu, F.; Zhang, Y.; Zhang, X.; Yuan, Q.; Li, Y. The m6A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network. Oncogene, 2019, 38(19), 3667-3680. doi: 10.1038/s41388-019-0683-z PMID: 30659266
  65. Aguilo, F.; Zhang, F.; Sancho, A.; Fidalgo, M.; Di Cecilia, S.; Vashisht, A.; Lee, D.F.; Chen, C.H.; Rengasamy, M.; Andino, B.; Jahouh, F.; Roman, A.; Krig, S.R.; Wang, R.; Zhang, W.; Wohlschlegel, J.A.; Wang, J.; Walsh, M.J. Coordination of m 6 A mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming. Cell Stem Cell, 2015, 17(6), 689-704. doi: 10.1016/j.stem.2015.09.005 PMID: 26526723
  66. Xie, J.; Ba, J.; Zhang, M.; Wan, Y.; Jin, Z.; Yao, Y. The m6A methyltransferase METTL3 promotes the stemness and malignant progression of breast cancer by mediating m6A modification on SOX2. J. BUON, 2021, 26(2), 444-449. PMID: 34076991
  67. Visvanathan, A.; Patil, V.; Arora, A.; Hegde, A.S.; Arivazhagan, A.; Santosh, V.; Somasundaram, K. Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance. Oncogene, 2018, 37(4), 522-533. doi: 10.1038/onc.2017.351 PMID: 28991227
  68. Li, T.; Hu, P.S.; Zuo, Z.; Lin, J.F.; Li, X.; Wu, Q.N.; Chen, Z.H.; Zeng, Z.L.; Wang, F.; Zheng, J.; Chen, D.; Li, B.; Kang, T.B.; Xie, D.; Lin, D.; Ju, H.Q.; Xu, R.H. METTL3 facilitates tumor progression via an m6A-IGF2BP2-dependent mechanism in colorectal carcinoma. Mol. Cancer, 2019, 18(1), 112. doi: 10.1186/s12943-019-1038-7 PMID: 31230592
  69. Galbraith, M.D.; Allen, M.A.; Bensard, C.L.; Wang, X.; Schwinn, M.K.; Qin, B.; Long, H.W.; Daniels, D.L.; Hahn, W.C.; Dowell, R.D.; Espinosa, J.M. HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia. Cell, 2013, 153(6), 1327-1339. doi: 10.1016/j.cell.2013.04.048 PMID: 23746844
  70. Lin, C.; Garrett, A.S.; De Kumar, B.; Smith, E.R.; Gogol, M.; Seidel, C.; Krumlauf, R.; Shilatifard, A. Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes Dev., 2011, 25(14), 1486-1498. doi: 10.1101/gad.2059211 PMID: 21764852
  71. Takahashi, H.; Parmely, T.J.; Sato, S.; Tomomori-Sato, C.; Banks, C.A.S.; Kong, S.E.; Szutorisz, H.; Swanson, S.K.; Martin-Brown, S.; Washburn, M.P.; Florens, L.; Seidel, C.W.; Lin, C.; Smith, E.R.; Shilatifard, A.; Conaway, R.C.; Conaway, J.W. Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell, 2011, 146(1), 92-104. doi: 10.1016/j.cell.2011.06.005 PMID: 21729782
  72. Erb, M.A.; Scott, T.G.; Li, B.E.; Xie, H.; Paulk, J.; Seo, H.S.; Souza, A.; Roberts, J.M.; Dastjerdi, S.; Buckley, D.L.; Sanjana, N.E.; Shalem, O.; Nabet, B.; Zeid, R.; Offei-Addo, N.K.; Dhe-Paganon, S.; Zhang, F.; Orkin, S.H.; Winter, G.E.; Bradner, J.E. Transcription control by the ENL YEATS domain in acute leukaemia. Nature, 2017, 543(7644), 270-274. doi: 10.1038/nature21688 PMID: 28241139
  73. Wan, L.; Wen, H.; Li, Y.; Lyu, J.; Xi, Y.; Hoshii, T.; Joseph, J.K.; Wang, X.; Loh, Y.H.E.; Erb, M.A.; Souza, A.L.; Bradner, J.E.; Shen, L.; Li, W.; Li, H.; Allis, C.D.; Armstrong, S.A.; Shi, X. ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature, 2017, 543(7644), 265-269. doi: 10.1038/nature21687 PMID: 28241141
  74. Armelin, H.A.; Armelin, M.C.S.; Kelly, K.; Stewart, T.; Leder, P.; Cochran, B.H.; Stiles, C.D. Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature, 1984, 310(5979), 655-660. doi: 10.1038/310655a0 PMID: 6088986
  75. Dang, C.V. MYC on the path to cancer. Cell, 2012, 149(1), 22-35. doi: 10.1016/j.cell.2012.03.003 PMID: 22464321
  76. Ross, J.; Miron, C.E.; Plescia, J.; Laplante, P.; McBride, K.; Moitessier, N.; Möröy, T. Targeting MYC: From understanding its biology to drug discovery. Eur. J. Med. Chem., 2021, 213, 113137. doi: 10.1016/j.ejmech.2020.113137 PMID: 33460833
  77. Liu, M.; Hsu, J.; Chan, C.; Li, Z.; Zhou, Q. The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription. Mol. Cell, 2012, 46(3), 325-334. doi: 10.1016/j.molcel.2012.03.007 PMID: 22483617
  78. Izumi, K.; Nakato, R.; Zhang, Z.; Edmondson, A.C.; Noon, S.; Dulik, M.C.; Rajagopalan, R.; Venditti, C.P.; Gripp, K.; Samanich, J.; Zackai, E.H.; Deardorff, M.A.; Clark, D.; Allen, J.L.; Dorsett, D.; Misulovin, Z.; Komata, M.; Bando, M.; Kaur, M.; Katou, Y.; Shirahige, K.; Krantz, I.D. Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat. Genet., 2015, 47(4), 338-344. doi: 10.1038/ng.3229 PMID: 25730767
  79. Liang, K.; Smith, E.R.; Aoi, Y.; Stoltz, K.L.; Katagi, H.; Woodfin, A.R.; Rendleman, E.J.; Marshall, S.A.; Murray, D.C.; Wang, L.; Ozark, P.A.; Mishra, R.K.; Hashizume, R.; Schiltz, G.E.; Shilatifard, A. Targeting processive transcription elongation via SEC disruption for MYC-induced cancer therapy. Cell, 2018, 175(3), 766-779.e17. doi: 10.1016/j.cell.2018.09.027 PMID: 30340042
  80. Larson, J.D.; Kasper, L.H.; Paugh, B.S.; Jin, H.; Wu, G.; Kwon, C.H.; Fan, Y.; Shaw, T.I.; Silveira, A.B.; Qu, C.; Xu, R.; Zhu, X.; Zhang, J.; Russell, H.R.; Peters, J.L.; Finkelstein, D.; Xu, B.; Lin, T.; Tinkle, C.L.; Patay, Z.; Onar-Thomas, A.; Pounds, S.B.; McKinnon, P.J.; Ellison, D.W.; Zhang, J.; Baker, S.J. Histone H3.3 K27M accelerates spontaneous brainstem glioma and drives restricted changes in bivalent gene expression. Cancer Cell, 2019, 35(1), 140-155.e7. doi: 10.1016/j.ccell.2018.11.015 PMID: 30595505
  81. Katagi, H.; Takata, N.; Aoi, Y.; Zhang, Y.; Rendleman, E.J.; Blyth, G.T.; Eckerdt, F.D.; Tomita, Y.; Sasaki, T.; Saratsis, A.M.; Kondo, A.; Goldman, S.; Becher, O.J.; Smith, E.; Zou, L.; Shilatifard, A.; Hashizume, R. Therapeutic targeting of transcriptional elongation in diffuse intrinsic pontine glioma. Neuro-oncol., 2021, 23(8), 1348-1359. doi: 10.1093/neuonc/noab009 PMID: 33471107
  82. Ni, C.; Liu, W.; Zheng, K.; Guo, S.; Song, B.; Jing, W.; Li, G.; Li, B.; Ni, C.; Shi, K.; Jin, G.; Yu, G. PI3K/c-Myc/AFF4 axis promotes pancreatic tumorigenesis through fueling nucleotide metabolism. Int. J. Biol. Sci., 2023, 19(6), 1968-1982. doi: 10.7150/ijbs.77150 PMID: 37063434
  83. Krivtsov, A.V.; Armstrong, S.A. MLL translocations, histone modifications and leukaemia stem-cell development. Nat. Rev. Cancer, 2007, 7(11), 823-833. doi: 10.1038/nrc2253 PMID: 17957188
  84. Liedtke, M.; Cleary, M.L. Therapeutic targeting of MLL. Blood, 2009, 113(24), 6061-6068. doi: 10.1182/blood-2008-12-197061 PMID: 19289854
  85. Chen, C.S.; Sorensen, P.H.; Domer, P.H.; Reaman, G.H.; Korsmeyer, S.J.; Heerema, N.A.; Hammond, G.D.; Kersey, J.H. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood, 1993, 81(9), 2386-2393. doi: 10.1182/blood.V81.9.2386.2386 PMID: 8481519
  86. Mrózek, K.; Heinonen, K.; Lawrence, D.; Carroll, A.J.; Koduru, P.R.K.; Rao, K.W.; Strout, M.P.; Hutchison, R.E.; Moore, J.O.; Mayer, R.J.; Schiffer, C.A.; Bloomfield, C.D. Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: A cancer and leukemia group B study. Blood, 1997, 90(11), 4532-4538. doi: 10.1182/blood.V90.11.4532 PMID: 9373264
  87. Hilden, J.M.; Dinndorf, P.A.; Meerbaum, S.O.; Sather, H.; Villaluna, D.; Heerema, N.A.; McGlennen, R.; Smith, F.O.; Woods, W.G.; Salzer, W.L.; Johnstone, H.S.; Dreyer, Z.; Reaman, G.H. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: Report on CCG 1953 from the Children’s Oncology Group. Blood, 2006, 108(2), 441-451. doi: 10.1182/blood-2005-07-3011 PMID: 16556894
  88. Wu, F.; Nie, S.; Yao, Y.; Huo, T.; Li, X.; Wu, X.; Zhao, J.; Lin, Y.L.; Zhang, Y.; Mo, Q.; Song, Y. Small-molecule inhibitor of AF9/ENL-DOT1L/AF4/AFF4 interactions suppresses malignant gene expression and tumor growth. Theranostics, 2021, 11(17), 8172-8184. doi: 10.7150/thno.56737 PMID: 34373735
  89. Meyer, C.; Burmeister, T.; Gröger, D.; Tsaur, G.; Fechina, L.; Renneville, A.; Sutton, R.; Venn, N.C.; Emerenciano, M.; Pombo-de-Oliveira, M.S.; Barbieri Blunck, C.; Almeida Lopes, B.; Zuna, J.; Trka, J.; Ballerini, P.; Lapillonne, H.; De Braekeleer, M.; Cazzaniga, G.; Corral Abascal, L.; van der Velden, V.H.J.; Delabesse, E.; Park, T.S.; Oh, S.H.; Silva, M.L.M.; Lund-Aho, T.; Juvonen, V.; Moore, A.S.; Heidenreich, O.; Vormoor, J.; Zerkalenkova, E.; Olshanskaya, Y.; Bueno, C.; Menendez, P.; Teigler-Schlegel, A.; zur Stadt, U.; Lentes, J.; Göhring, G.; Kustanovich, A.; Aleinikova, O.; Schäfer, B.W.; Kubetzko, S.; Madsen, H.O.; Gruhn, B.; Duarte, X.; Gameiro, P.; Lippert, E.; Bidet, A.; Cayuela, J.M.; Clappier, E.; Alonso, C.N.; Zwaan, C.M.; van den Heuvel-Eibrink, M.M.; Izraeli, S.; Trakhtenbrot, L.; Archer, P.; Hancock, J.; Möricke, A.; Alten, J.; Schrappe, M.; Stanulla, M.; Strehl, S.; Attarbaschi, A.; Dworzak, M.; Haas, O.A.; Panzer-Grümayer, R.; Sedék, L. Szczepański, T.; Caye, A.; Suarez, L.; Cavé, H.; Marschalek, R. The MLL recombinome of acute leukemias in 2017. Leukemia, 2018, 32(2), 273-284. doi: 10.1038/leu.2017.213 PMID: 28701730
  90. Lin, C.; Smith, E.R.; Takahashi, H.; Lai, K.C.; Martin-Brown, S.; Florens, L.; Washburn, M.P.; Conaway, J.W.; Conaway, R.C.; Shilatifard, A. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol. Cell, 2010, 37(3), 429-437. doi: 10.1016/j.molcel.2010.01.026 PMID: 20159561
  91. Kuntimaddi, A.; Achille, N.J.; Thorpe, J.; Lokken, A.A.; Singh, R.; Hemenway, C.S.; Adli, M.; Zeleznik-Le, N.J.; Bushweller, J.H. Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential. Cell Rep., 2015, 11(5), 808-820. doi: 10.1016/j.celrep.2015.04.004 PMID: 25921540
  92. Feng, Q.; Wang, H.; Ng, H.H.; Erdjument-Bromage, H.; Tempst, P.; Struhl, K.; Zhang, Y. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr. Biol., 2002, 12(12), 1052-1058. doi: 10.1016/S0960-9822(02)00901-6 PMID: 12123582
  93. Okada, Y.; Feng, Q.; Lin, Y.; Jiang, Q.; Li, Y.; Coffield, V.M.; Su, L.; Xu, G.; Zhang, Y. hDOT1L links histone methylation to leukemogenesis. Cell, 2005, 121(2), 167-178. doi: 10.1016/j.cell.2005.02.020 PMID: 15851025
  94. Dustin, D.; Gu, G.; Fuqua, S.A.W. ESR1 mutations in breast cancer. Cancer, 2019, 125(21), 3714-3728. doi: 10.1002/cncr.32345 PMID: 31318440
  95. Reinert, T.; Gonçalves, R.; Bines, J. Implications of ESR1 mutations in hormone receptor-positive breast cancer. Curr. Treat. Options Oncol., 2018, 19(5), 24. doi: 10.1007/s11864-018-0542-0 PMID: 29666928
  96. Itoh, M.; Iwamoto, T.; Matsuoka, J.; Nogami, T.; Motoki, T.; Shien, T.; Taira, N.; Niikura, N.; Hayashi, N.; Ohtani, S.; Higaki, K.; Fujiwara, T.; Doihara, H.; Symmans, W.F.; Pusztai, L. Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers. Breast Cancer Res. Treat., 2014, 143(2), 403-409. doi: 10.1007/s10549-013-2763-z PMID: 24337596
  97. Fuqua, S.A.W.; Gu, G.; Rechoum, Y. Estrogen receptor (ER) α mutations in breast cancer: Hidden in plain sight. Breast Cancer Res. Treat., 2014, 144(1), 11-19. doi: 10.1007/s10549-014-2847-4 PMID: 24487689
  98. Gao, Y.; Chen, L.; Han, Y.; Wu, F.; Yang, W.S.; Zhang, Z.; Huo, T.; Zhu, Y.; Yu, C.; Kim, H.; Lee, M.; Tang, Z.; Phillips, K.; He, B.; Jung, S.Y.; Song, Y.; Zhu, B.; Xu, R.M.; Feng, Q. Acetylation of histone H3K27 signals the transcriptional elongation for estrogen receptor alpha. Commun. Biol., 2020, 3(1), 165. doi: 10.1038/s42003-020-0898-0 PMID: 32265480
  99. Yu, H.; Lin, L.; Zhang, Z.; Zhang, H.; Hu, H. Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct. Target. Ther., 2020, 5(1), 209. doi: 10.1038/s41392-020-00312-6 PMID: 32958760
  100. Meng, Q.; Xia, Y. c-Jun, at the crossroad of the signaling network. Protein Cell, 2011, 2(11), 889-898. doi: 10.1007/s13238-011-1113-3 PMID: 22180088
  101. Hu, H.; Zhang, Y.; Zhao, L.; Zhao, W.; Wang, X.; Ye, E.; Dong, Y.; Zhang, L.; Ran, F.; Zhou, Y.; Huang, Y. AFF4 facilitates melanoma cell progression by regulating c-Jun activity. Exp. Cell Res., 2021, 399(2), 112445. doi: 10.1016/j.yexcr.2020.112445 PMID: 33417923
  102. Liao, C.; Wang, Q.; An, J.; Long, Q.; Wang, H.; Xiang, M.; Xiang, M.; Zhao, Y.; Liu, Y.; Liu, J.; Guan, X. Partial EMT in squamous cell carcinoma: A snapshot. Int. J. Biol. Sci., 2021, 17(12), 3036-3047. doi: 10.7150/ijbs.61566 PMID: 34421348
  103. Kong, F.; Deng, X.; Kong, X.; Du, Y.; Li, L.; Zhu, H.; Wang, Y.; Xie, D.; Guha, S.; Li, Z.; Guan, M.; Xie, K. ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes gastric carcinogenesis by stabilizing MIF. Oncogene, 2018, 37(45), 5982-5996. doi: 10.1038/s41388-018-0387-9 PMID: 29985481
  104. Sun, G.; Wu, C. ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4. Biosci. Rep., 2020, 40(4), BSR20194352. doi: 10.1042/BSR20194352 PMID: 32065218
  105. Zhao, Y.F.; Li, L.; Li, H.J.; Yang, F.R.; Liu, Z.K.; Hu, X.W.; Wang, Q. LncRNA ZFPM2-AS1 aggravates the malignant development of breast cancer via upregulating JMJD6. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(21), 11139-11147. doi: 10.26355/eurrev_202011_23601 PMID: 33215431
  106. Liu, W.; Zhang, G.Q.; Zhu, D.Y.; Wang, L.J.; Li, G.T.; Xu, J.G.; Jin, X.L.; Zhu, Y.M.; Yang, X.Y. Long noncoding RNA ZFPM2-AS1 regulates ITGB1 by miR-1226-3p to promote cell proliferation and invasion in hepatocellular carcinoma. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(14), 7612-7620. doi: 10.26355/eurrev_202007_22259 PMID: 32744687
  107. Liu, J.G.; Wang, H.B.; Wan, G.; Yang, M.Z.; Jiang, X.J.; Yang, J.Y. Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(18), 9238. doi: 10.26355/eurrev_202009_22996 PMID: 33015759
  108. Lyv, X.; Wu, F.; Zhang, H.; Lu, J.; Wang, L.; Ma, Y. Long Noncoding RNA ZFPM2-AS1 knockdown restrains the development of retinoblastoma by modulating the microRNA-515/HOXA1/Wnt/β-. Catenin Axis. Invest. Ophthalmol. Vis. Sci., 2020, 61(6), 41. doi: 10.1167/iovs.61.6.41 PMID: 32561925
  109. Han, S.; Cao, D.; Sha, J.; Zhu, X.; Chen, D. LncRNA ZFPM2‐AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2. Mol. Oncol., 2020, 14(5), 1074-1088. doi: 10.1002/1878-0261.12631 PMID: 31919993
  110. Li, J.; Ge, J.; Yang, Y.; Liu, B.; Zheng, M.; Shi, R. Retracted:Long noncoding RNA ZFPM2‐AS1 is involved in lung adenocarcinoma via miR‐511‐3p/AFF4 pathway. J. Cell. Biochem., 2020, 121(3), 2534-2542. doi: 10.1002/jcb.29476 PMID: 31692047
  111. Hillman, M.A.; Gecz, J. Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator. J. Hum. Genet., 2001, 46(5), 251-259. doi: 10.1007/s100380170074 PMID: 11355014
  112. Ma, C.; Staudt, L.M. LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias. Blood, 1996, 87(2), 734-745. doi: 10.1182/blood.V87.2.734.bloodjournal872734 PMID: 8555498
  113. Mak, A.B.; Nixon, A.M.L.; Moffat, J. The mixed lineage leukemia (MLL) fusion-associated gene AF4 promotes CD133 transcription. Cancer Res., 2012, 72(8), 1929-1934. doi: 10.1158/0008-5472.CAN-11-3589 PMID: 22337994
  114. Lu, H.; Li, Z.; Xue, Y.; Schulze-Gahmen, U.; Johnson, J.R.; Krogan, N.J.; Alber, T.; Zhou, Q. AFF1 is a ubiquitous P-TEFb partner to enable Tat extraction of P-TEFb from 7SK snRNP and formation of SECs for HIV transactivation. Proc. Natl. Acad. Sci. USA, 2014, 111(1), E15-E24. doi: 10.1073/pnas.1318503111 PMID: 24367103
  115. Melko, M.; Douguet, D.; Bensaid, M.; Zongaro, S.; Verheggen, C.; Gecz, J.; Bardoni, B. Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability. Hum. Mol. Genet., 2011, 20(10), 1873-1885. doi: 10.1093/hmg/ddr069 PMID: 21330300
  116. Biswas, D.; Milne, T.A.; Basrur, V.; Kim, J.; Elenitoba-Johnson, K.S.J.; Allis, C.D.; Roeder, R.G. Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes. Proc. Natl. Acad. Sci., 2011, 108(38), 15751-15756. doi: 10.1073/pnas.1111498108 PMID: 21896721
  117. Liu, K.; Shen, D.; Shen, J.; Gao, S.M.; Li, B.; Wong, C.; Feng, W.; Song, Y. The super elongation complex drives neural stem cell fate commitment. Dev. Cell, 2017, 40(6), 537-551.e6. doi: 10.1016/j.devcel.2017.02.022 PMID: 28350987
  118. Yoshida, G.J. Emerging roles of Myc in stem cell biology and novel tumor therapies. J. Exp. Clin. Cancer Res., 2018, 37(1), 173. doi: 10.1186/s13046-018-0835-y PMID: 30053872

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