Advertisement

Apoptosis

, Volume 24, Issue 1–2, pp 108–118 | Cite as

MicroRNA-663 antagonizes apoptosis antagonizing transcription factor to induce apoptosis in epithelial cells

  • M. R. BenakanakereEmail author
  • J. Zhao
  • L. Finoti
  • R. Schattner
  • M. Odabas-Yigit
  • D. F. Kinane
Article
  • 286 Downloads

Abstract

MicroRNAs are small functional RNAs that modulate various biological processes in cells by interfering with gene translation. We have previously demonstrated that certain miRNAs play a crucial role in the innate immune responses of human oral epithelial cells to Porphyromonas gingivalis. While addressing the mechanisms of P. gingivalis induced apoptosis in these cells, we discovered that certain miRNAs are upregulated upon stimulation with live bacteria. These upregulated miRNAs include hsa-miR-584, hsa-miR-572, hsa-miR-210, hsa-miR-492, hsa-miR-623 and hsa-miR-663. Further analysis revealed an unexpected role for hsa-miR-663 (miR-663). To further evaluate miR-663 function, we overexpressed miR-663 in epithelial cells which resulted in cellular apoptosis. The bioinformatics analysis of the miR-663 target prediction, revealed a strong binding affinity to a 3′ UTR region of Apoptosis Antagonizing Transcription Factor (AATF) mRNA. To demonstrate the binding of miR-663 to AATF mRNA, the putative miR-663 target site within the 3′-UTR region of AATF was cloned in luciferase vector and transfected to HEK293T cells. Luminescence data showed the downregulation of luciferase activity in cells that had the full length target region of the putative binding site, confirming that AATF is one of the targets for miR-663. This prompted us to further evaluate its role in a cancer cell line (MCF-7) to determine miR-663s’ apoptotic function. The overexpression of miR-663 led to a significant increase in apoptosis of MCF-7 cells. Taken together, miR-663 may function as an ‘apoptomiR’ by inhibiting the anti-apoptotic gene AATF to induce apoptosis. These findings could have therapeutic implications for epithelial cell targeting in cancer therapy.

Keywords

Porphyromonas gingivalis MicroRNAs Primary oral epithelial cells Cell death ApoptomiRs 

Notes

Acknowledgements

This work was supported in part by National Institutes of Health Grant (R01DE024160). BMR is a recipient of Rabinowitz award for research excellence and thanks the Rabinowitz family for their generous support.

Supplementary material

10495_2018_1513_MOESM1_ESM.docx (128 kb)
Supplementary material 1 (DOCX 128 KB)

References

  1. 1.
    Benakanakere M, Kinane DF (2012) Innate cellular responses to the periodontal biofilm. Front Oral Biol 15:41–55.  https://doi.org/10.1159/000329670 Google Scholar
  2. 2.
    Kinane DF, Galicia JC, Gorr SU, Stathopoulou PG, Benakanakere M (2008) P. gingivalis interactions with epithelial cells. Front Biosci 13:966–984Google Scholar
  3. 3.
    Kinane JA, Benakanakere MR, Zhao J, Hosur KB, Kinane DF (2012) Porphyromonas gingivalis influences actin degradation within epithelial cells during invasion and apoptosis. Cell Microbiol 14(7):1085–1096.  https://doi.org/10.1111/j.1462-5822.2012.01780.x Google Scholar
  4. 4.
    Stathopoulou PG, Benakanakere MR, Galicia JC, Kinane DF (2009) The host cytokine response to Porphyromonas gingivalis is modified by gingipains. Oral Microbiol Immunol 24(1):11–17.  https://doi.org/10.1111/j.1399-302X.2008.00467.x Google Scholar
  5. 5.
    Stathopoulou PG, Galicia JC, Benakanakere MR, Garcia CA, Potempa J, Kinane DF (2009) Porphyromonas gingivalis induce apoptosis in human gingival epithelial cells through a gingipain-dependent mechanism. BMC Microbiol 9:107.  https://doi.org/10.1186/1471-2180-9-107 Google Scholar
  6. 6.
    Kiraz Y, Adan A, Kartal Yandim M, Baran Y (2016) Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biol 37(7):8471–8486.  https://doi.org/10.1007/s13277-016-5035-9 Google Scholar
  7. 7.
    Koulouri O, Lappin DF, Radvar M, Kinane DF (1999) Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridisation and immunohistochemistry. J Clin Periodontol 26(8):552–559Google Scholar
  8. 8.
    Tonetti MS, Cortellini D, Lang NP (1998) In situ detection of apoptosis at sites of chronic bacterially induced inflammation in human gingiva. Infect Immun 66(11):5190–5195Google Scholar
  9. 9.
    Brozovic S, Sahoo R, Barve S, Shiba H, Uriarte S, Blumberg RS, Kinane DF (2006) Porphyromonas gingivalis enhances FasL expression via up-regulation of NFkappaB-mediated gene transcription and induces apoptotic cell death in human gingival epithelial cells. Microbiology 152(Pt 3):797–806.  https://doi.org/10.1099/mic.0.28472-0 Google Scholar
  10. 10.
    Galicia JC, Benakanakere MR, Stathopoulou PG, Kinane DF (2009) Neutrophils rescue gingival epithelial cells from bacterial-induced apoptosis. J Leukoc Biol 86(1):181–186.  https://doi.org/10.1189/jlb.0109003 Google Scholar
  11. 11.
    Imatani T, Kato T, Okuda K, Yamashita Y (2004) Histatin 5 inhibits apoptosis in human gingival fibroblasts induced by Porphyromonas gingivalis cell-surface polysaccharide. Eur J Med Res 9(11):528–532Google Scholar
  12. 12.
    Urnowey S, Ansai T, Bitko V, Nakayama K, Takehara T, Barik S (2006) Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling. BMC Microbiol 6:26Google Scholar
  13. 13.
    Kobayashi-Sakamoto M, Hirose K, Nishikata M, Isogai E, Chiba I (2006) Osteoprotegerin protects endothelial cells against apoptotic cell death induced by Porphyromonas gingivalis cysteine proteinases. FEMS Microbiol Lett 264(2):238–245Google Scholar
  14. 14.
    Roth GA, Ankersmit HJ, Brown VB, Papapanou PN, Schmidt AM, Lalla E (2007) Porphyromonas gingivalis infection and cell death in human aortic endothelial cells. FEMS Microbiol Lett 272(1):106–113Google Scholar
  15. 15.
    Sheets SM, Potempa J, Travis J, Casiano CA, Fletcher HM (2005) Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule cleavage and apoptosis in endothelial cells. Infect Immun 73(3):1543–1552Google Scholar
  16. 16.
    Sheets SM, Potempa J, Travis J, Fletcher HM, Casiano CA (2006) Gingipains from Porphyromonas gingivalis W83 synergistically disrupt endothelial cell adhesion and can induce caspase-independent apoptosis. Infect Immun 74(10):5667–5678Google Scholar
  17. 17.
    Geatch DR, Harris JI, Heasman PA, Taylor JJ (1999) In vitro studies of lymphocyte apoptosis induced by the periodontal pathogen Porphyromonas gingivalis. J Periodontal Res 34(2):70–78Google Scholar
  18. 18.
    Vecchione A, Croce CM (2010) Apoptomirs: small molecules have gained the license to kill. Endocr Relat Cancer 17(1):F37–F50.  https://doi.org/10.1677/erc-09-0163 Google Scholar
  19. 19.
    Burin SM, Berzoti-Coelho MG, Cominal JG, Ambrosio L, Torqueti MR, Sampaio SV, de Castro FA (2016) The L-amino acid oxidase from Calloselasma rhodostoma snake venom modulates apoptomiRs expression in Bcr-Abl-positive cell lines. Toxicon 120:9–14.  https://doi.org/10.1016/j.toxicon.2016.07.008 Google Scholar
  20. 20.
    Sharma S, Patnaik PK, Aronov S, Kulshreshtha R (2016) ApoptomiRs of breast cancer: basics to clinics. Front Genet 7:175.  https://doi.org/10.3389/fgene.2016.00175 Google Scholar
  21. 21.
    Wald AI, Hoskins EE, Wells SI, Ferris RL, Khan SA (2011) Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head Neck 33(4):504–512.  https://doi.org/10.1002/hed.21475 Google Scholar
  22. 22.
    Benakanakere MR, Li Q, Eskan MA, Singh AV, Zhao J, Galicia JC, Stathopoulou P, Knudsen TB, Kinane DF (2009) Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes. J Biol Chem 284(34):23107–23115.  https://doi.org/10.1074/jbc.M109.013862 Google Scholar
  23. 23.
    Chen Y, Fu LL, Wen X, Liu B, Huang J, Wang JH, Wei YQ (2014) Oncogenic and tumor suppressive roles of microRNAs in apoptosis and autophagy. Apoptosis 19(8):1177–1189.  https://doi.org/10.1007/s10495-014-0999-7 Google Scholar
  24. 24.
    Nakano H, Miyazawa T, Kinoshita K, Yamada Y, Yoshida T (2010) Functional screening identifies a microRNA, miR-491 that induces apoptosis by targeting Bcl-X(L) in colorectal cancer cells. Int J Cancer 127(5):1072–1080.  https://doi.org/10.1002/ijc.25143 Google Scholar
  25. 25.
    Chen Q, Xu J, Li L, Li H, Mao S, Zhang F, Zen K, Zhang CY, Zhang Q (2014) MicroRNA-23a/b and microRNA-27a/b suppress Apaf-1 protein and alleviate hypoxia-induced neuronal apoptosis. Cell Death Dis 5:e1132.  https://doi.org/10.1038/cddis.2014.92 Google Scholar
  26. 26.
    Lin YC, Lin JF, Tsai TF, Chou KY, Chen HE, Hwang TI (2016) Tumor suppressor miRNA-204-5p promotes apoptosis by targeting BCL2 in prostate cancer cells. Asian J Surg.  https://doi.org/10.1016/j.asjsur.2016.07.001 Google Scholar
  27. 27.
    Lin Z, Zhao J, Wang X, Zhu X, Gong L (2016) Overexpression of microRNA-497 suppresses cell proliferation and induces apoptosis through targeting paired box 2 in human ovarian cancer. Oncol Rep 36(4):2101–2107.  https://doi.org/10.3892/or.2016.5012 Google Scholar
  28. 28.
    Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102(39):13944–13949.  https://doi.org/10.1073/pnas.0506654102 Google Scholar
  29. 29.
    Garofalo M, Quintavalle C, Di Leva G, Zanca C, Romano G, Taccioli C, Liu CG, Croce CM, Condorelli G (2008) MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene 27(27):3845–3855.  https://doi.org/10.1038/onc.2008.6 Google Scholar
  30. 30.
    Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26(5):745–752.  https://doi.org/10.1016/j.molcel.2007.05.010 Google Scholar
  31. 31.
    He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, Jackson AL, Linsley PS, Chen C, Lowe SW, Cleary MA, Hannon GJ (2007) A microRNA component of the p53 tumour suppressor network. Nature 447(7148):1130–1134.  https://doi.org/10.1038/nature05939 Google Scholar
  32. 32.
    Petrocca F, Visone R, Onelli MR, Shah MH, Nicoloso MS, de Martino I, Iliopoulos D, Pilozzi E, Liu CG, Negrini M, Cavazzini L, Volinia S, Alder H, Ruco LP, Baldassarre G, Croce CM, Vecchione A (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13(3):272–286.  https://doi.org/10.1016/j.ccr.2008.02.013 Google Scholar
  33. 33.
    Zhao J, Benakanakere MR, Hosur KB, Galicia JC, Martin M, Kinane DF (2010) Mammalian target of rapamycin (mTOR) regulates TLR3 induced cytokines in human oral keratinocytes. Mol Immunol 48(1–3):294–304.  https://doi.org/10.1016/j.molimm.2010.07.014 Google Scholar
  34. 34.
    Benakanakere M, Abdolhosseini M, Hosur K, Finoti LS, Kinane DF (2015) TLR2 promoter hypermethylation creates innate immune dysbiosis. J Dent Res 94(1):183–191.  https://doi.org/10.1177/0022034514557545 Google Scholar
  35. 35.
    Benakanakere MR, Zhao J, Galicia JC, Martin M, Kinane DF (2010) Sphingosine kinase-1 is required for toll mediated beta-defensin 2 induction in human oral keratinocytes. PLoS ONE 5(7):e11512.  https://doi.org/10.1371/journal.pone.0011512 Google Scholar
  36. 36.
    Eskan MA, Benakanakere MR, Rose BG, Zhang P, Zhao J, Stathopoulou P, Fujioka D, Kinane DF (2008) Interleukin-1beta modulates proinflammatory cytokine production in human epithelial cells. Infect Immun 76(5):2080–2089.  https://doi.org/10.1128/IAI.01428-07 Google Scholar
  37. 37.
    Stathopoulou PG, Benakanakere MR, Galicia JC, Kinane DF (2010) Epithelial cell pro-inflammatory cytokine response differs across dental plaque bacterial species. J Clin Periodontol 37(1):24–29.  https://doi.org/10.1111/j.1600-051X.2009.01505.x Google Scholar
  38. 38.
    Eskan MA, Rose BG, Benakanakere MR, Zeng Q, Fujioka D, Martin MH, Lee MJ, Kinane DF (2008) TLR4 and S1P receptors cooperate to enhance inflammatory cytokine production in human gingival epithelial cells. Eur J Immunol 38(4):1138–1147.  https://doi.org/10.1002/eji.200737898 Google Scholar
  39. 39.
    Eskan MA, Rose BG, Benakanakere MR, Lee MJ, Kinane DF (2008) Sphingosine 1-phosphate 1 and TLR4 mediate IFN-beta expression in human gingival epithelial cells. J Immunol 180(3):1818–1825Google Scholar
  40. 40.
    Kinane DF, Shiba H, Stathopoulou PG, Zhao H, Lappin DF, Singh A, Eskan MA, Beckers S, Waigel S, Alpert B, Knudsen TB (2006) Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399ile are hypo-responsive to Porphyromonas gingivalis. Genes Immun 7(3):190–200.  https://doi.org/10.1038/sj.gene.6364282 Google Scholar
  41. 41.
    Eisen MB, Spellman PT, Brown PO, Botstein D (1998) Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA 95(25):14863–14868Google Scholar
  42. 42.
    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(4):402–408.  https://doi.org/10.1006/meth.2001.1262S1046-2023(01)91262-9 Google Scholar
  43. 43.
    Yi C, Wang Q, Wang L, Huang Y, Li L, Liu L, Zhou X, Xie G, Kang T, Wang H, Zeng M, Ma J, Zeng Y, Yun JP (2012) MiR-663, a microRNA targeting p21(WAF1/CIP1), promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma. Oncogene 31(41):4421–4433.  https://doi.org/10.1038/onc.2011.629 Google Scholar
  44. 44.
    Zang W, Wang Y, Wang T, Du Y, Chen X, Li M, Zhao G (2015) miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer. Mol Cancer 14:37.  https://doi.org/10.1186/s12943-015-0315-3 Google Scholar
  45. 45.
    Zhang Y, Xu X, Zhang M, Wang X, Bai X, Li H, Kan L, Zhou Y, Niu H, He P (2016) MicroRNA-663a is downregulated in non-small cell lung cancer and inhibits proliferation and invasion by targeting JunD. BMC Cancer 16:315.  https://doi.org/10.1186/s12885-016-2350-x Google Scholar
  46. 46.
    Liu J, Drescher KM, Chen X-M (2009) MicroRNAs and epithelial immunity. Int Rev Immunol 28(3–4):139–154.  https://doi.org/10.1080/08830180902943058 doiGoogle Scholar
  47. 47.
    Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39(Database issue):D152–D157.  https://doi.org/10.1093/nar/gkq1027 Google Scholar
  48. 48.
    Munker R, Calin GA (2011) MicroRNA profiling in cancer. Clin Sci 121(4):141–158.  https://doi.org/10.1042/CS20110005 Google Scholar
  49. 49.
    Babar IA, Cheng CJ, Booth CJ, Liang X, Weidhaas JB, Saltzman WM, Slack FJ (2012) Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci USA 109(26):E1695–E1704.  https://doi.org/10.1073/pnas.1201516109 Google Scholar
  50. 50.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269.  https://doi.org/10.1038/nrc1840 Google Scholar
  51. 51.
    Medina PP, Nolde M, Slack FJ (2010) OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467(7311):86–90.  https://doi.org/10.1038/nature09284 Google Scholar
  52. 52.
    Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C, Svoronos A, Braddock DT, Glazer PM, Engelman DM, Saltzman WM, Slack FJ (2015) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 518(7537):107–110.  https://doi.org/10.1038/nature13905 Google Scholar
  53. 53.
    Jian P, Li ZW, Fang TY, Jian W, Zhuan Z, Mei LX, Yan WS, Jian N (2011) Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663. J Hematol Oncol 4:20.  https://doi.org/10.1186/1756-8722-4-20 Google Scholar
  54. 54.
    Ni CW, Qiu H, Jo H (2011) MicroRNA-663 upregulated by oscillatory shear stress plays a role in inflammatory response of endothelial cells. Am J Physiol Heart Circ Physiol 300(5):H1762–H1769.  https://doi.org/10.1152/ajpheart.00829.2010 Google Scholar
  55. 55.
    Hu H, Li S, Cui X, Lv X, Jiao Y, Yu F, Yao H, Song E, Chen Y, Wang M, Lin L (2013) The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2). J Biol Chem 288(16):10973–10985.  https://doi.org/10.1074/jbc.M112.434340 Google Scholar
  56. 56.
    Pan J, Hu H, Zhou Z, Sun L, Peng L, Yu L, Sun L, Liu J, Yang Z, Ran Y (2010) Tumor-suppressive mir-663 gene induces mitotic catastrophe growth arrest in human gastric cancer cells. Oncol Rep 24(1):105–112Google Scholar
  57. 57.
    Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, Ferracin M, Delmas D, Latruffe N, Croce CM (2010) Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis 31(9):1561–1566.  https://doi.org/10.1093/carcin/bgq143 Google Scholar
  58. 58.
    Pisani C, Onori A, Gabanella F, Delle Monache F, Borreca A, Ammassari-Teule M, Fanciulli M, Di Certo MG, Passananti C, Corbi N (2016) eEF1Bgamma binds the Che-1 and TP53 gene promoters and their transcripts. J Exp Clin Cancer Res 35(1):146.  https://doi.org/10.1186/s13046-016-0424-x Google Scholar
  59. 59.
    Bruno T, Iezzi S, Fanciulli M (2016) Che-1/AATF: a critical cofactor for both wild-type- and mutant-p53 proteins. Front Oncol 6:34.  https://doi.org/10.3389/fonc.2016.00034 Google Scholar
  60. 60.
    Passananti C, Fanciulli M (2007) The anti-apoptotic factor Che-1/AATF links transcriptional regulation, cell cycle control, and DNA damage response. Cell Div 2:21.  https://doi.org/10.1186/1747-1028-2-21 Google Scholar
  61. 61.
    Jackson JG, Lozano G (2012) Che-ating death: CHE1/AATF protects from p53-mediated apoptosis. EMBO J 31(20):3951–3953.  https://doi.org/10.1038/emboj.2012.258 Google Scholar
  62. 62.
    Iezzi S, Fanciulli M (2015) Discovering Che-1/AATF: a new attractive target for cancer therapy. Front Genet 6:141.  https://doi.org/10.3389/fgene.2015.00141 Google Scholar
  63. 63.
    Folgiero V, Sorino C, Locatelli F, Fanciulli M (2018) A new baby in the c-Myc-directed transcriptional machinery: Che-1/AATF. Cell Cycle 17(11):1286–1290.  https://doi.org/10.1080/15384101.2018.1480227 Google Scholar
  64. 64.
    Folgiero V, Sorino C, Pallocca M, De Nicola F, Goeman F, Bertaina V, Strocchio L, Romania P, Pitisci A, Iezzi S, Catena V, Bruno T, Strimpakos G, Passananti C, Mattei E, Blandino G, Locatelli F, Fanciulli M (2018) Che-1 is targeted by c-Myc to sustain proliferation in pre-B-cell acute lymphoblastic leukemia. EMBO Rep.  https://doi.org/10.15252/embr.201744871 Google Scholar
  65. 65.
    Di Certo MG, Corbi N, Bruno T, Iezzi S, De Nicola F, Desantis A, Ciotti MT, Mattei E, Floridi A, Fanciulli M, Passananti C (2007) NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. J Cell Sci 120(Pt 11):1852–1858.  https://doi.org/10.1242/jcs.03454 Google Scholar
  66. 66.
    Guo Q, Xie J (2004) AATF inhibits aberrant production of amyloid beta peptide 1–42 by interacting directly with Par-4. J Biol Chem 279(6):4596–4603.  https://doi.org/10.1074/jbc.M309811200 Google Scholar
  67. 67.
    Xie J, Guo Q (2004) AATF protects neural cells against oxidative damage induced by amyloid beta-peptide. Neurobiol Dis 16(1):150–157.  https://doi.org/10.1016/j.nbd.2004.02.003 Google Scholar
  68. 68.
    Ferraris SE, Isoniemi K, Torvaldson E, Anckar J, Westermarck J, Eriksson JE (2012) Nucleolar AATF regulates c-Jun-mediated apoptosis. Mol Biol Cell 23(21):4323–4332.  https://doi.org/10.1091/mbc.E12-05-0419 Google Scholar
  69. 69.
    Bruno T, Valerio M, Casadei L, De Nicola F, Goeman F, Pallocca M, Catena V, Iezzi S, Sorino C, Desantis A, Manetti C, Blandino G, Floridi A, Fanciulli M (2017) Che-1 sustains hypoxic response of colorectal cancer cells by affecting Hif-1alpha stabilization. J Exp Clin Cancer Res 36(1):32.  https://doi.org/10.1186/s13046-017-0497-1 Google Scholar
  70. 70.
    Bruno T, De Angelis R, De Nicola F, Barbato C, Di Padova M, Corbi N, Libri V, Benassi B, Mattei E, Chersi A, Soddu S, Floridi A, Passananti C, Fanciulli M (2002) Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb. Cancer Cell 2(5):387–399Google Scholar
  71. 71.
    Bruno T, De Nicola F, Iezzi S, Lecis D, D’Angelo C, Di Padova M, Corbi N, Dimiziani L, Zannini L, Jekimovs C, Scarsella M, Porrello A, Chersi A, Crescenzi M, Leonetti C, Khanna KK, Soddu S, Floridi A, Passananti C, Delia D, Fanciulli M (2006) Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer Cell 10(6):473–486.  https://doi.org/10.1016/j.ccr.2006.10.012 Google Scholar
  72. 72.
    Ishigaki S, Fonseca SG, Oslowski CM, Jurczyk A, Shearstone JR, Zhu LJ, Permutt MA, Greiner DL, Bortell R, Urano F (2010) AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional regulation of AKT1. Cell Death Differ 17(5):774–786.  https://doi.org/10.1038/cdd.2009.175 Google Scholar
  73. 73.
    Kumar DP, Santhekadur PK, Seneshaw M, Mirshahi F, Tuculescu CU, Sanyal AJ (2018) A novel regulatory role of apoptosis antagonizing transcription factor in the pathogenesis of NAFLD and HCC. Hepatology.  https://doi.org/10.1002/hep.30346 Google Scholar
  74. 74.
    Welcker D, Jain M, Khurshid S, Jokic M, Hohne M, Schmitt A, Frommolt P, Niessen CM, Spiro J, Persigehl T, Wittersheim M, Buttner R, Fanciulli M, Schermer B, Reinhardt HC, Benzing T, Hopker K (2018) AATF suppresses apoptosis, promotes proliferation and is critical for Kras-driven lung cancer. Oncogene 37(11):1503–1518.  https://doi.org/10.1038/s41388-017-0054-6 Google Scholar
  75. 75.
    Sharma S, Kaul D, Arora M, Malik D (2015) Oncogenic nature of a novel mutant AATF and its interactome existing within human cancer cells. Cell Biol Int 39(3):326–333.  https://doi.org/10.1002/cbin.10379 Google Scholar
  76. 76.
    Sharma M (2013) Apoptosis-antagonizing transcription factor (AATF) gene silencing: role in induction of apoptosis and down-regulation of estrogen receptor in breast cancer cells. Biotechnol Lett 35(10):1561–1570.  https://doi.org/10.1007/s10529-013-1257-8 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • M. R. Benakanakere
    • 1
    Email author
  • J. Zhao
    • 2
    • 3
  • L. Finoti
    • 1
  • R. Schattner
    • 1
  • M. Odabas-Yigit
    • 1
  • D. F. Kinane
    • 4
  1. 1.Department of Periodontics, School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Pathology, School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PathologyWayne State University School of MedicineDetroitUSA
  4. 4.Division of Periodontology, School of Dental MedicineUniversity of Geneva Faculty of MedicineGenevaSwitzerland

Personalised recommendations