Skip to main content

Advertisement

SpringerLink
Log in

The function of brother of the regulator of imprinted sites in cancer development

  • Review Article
  • Published:
Cancer Gene Therapy Submit manuscript

Abstract

As Douglas Hanahan and Robert Weinberg compiled, there are nine hallmarks of cancer that are conducive to cancer cell development and survival. Previous studies showed that brother of the regulator of imprinted sites (BORIS) might promote cancer progression through these aspects. The competition between BORIS and CCCTC-binding factor (CTCF), which is crucial in the formation of chromatin loops, affects the normal function of CTCF and leads to neoplasia and deformity. In addition, BORIS belongs to the cancer-testis antigen families, which are potential targets in cancer diagnosis and treatment. Herein, we discuss the function and mechanisms of BORIS, especially in cancer development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: The role of BORIS in cancer initiation and progression.
Fig. 2: The role of BORIS in spermatogenesis and embryo development.

Similar content being viewed by others

References

  1. Loukinov DI, Pugacheva E, Vatolin S, Pack SD, Moon H, Chernukhin I, et al. BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proc Natl Acad Sci USA. 2002;99:6806–11.

    Article  CAS  Google Scholar 

  2. Pugacheva EM, Suzuki T, Pack SD, Kosaka-Suzuki N, Yoon J, Vostrov AA, et al. The structural complexity of the human BORIS gene in gametogenesis and cancer. PLoS ONE. 2010;5:e13872.

    Article  Google Scholar 

  3. Freitas M, Malheiros S, Stávale JN, Biassi TP, Zamunér FT, de Souza Begnami M, et al. Expression of cancer/testis antigens is correlated with improved survival in glioblastoma. Oncotarget. 2013;4:636–46.

    Article  Google Scholar 

  4. Martin-Kleiner I. BORIS in human cancers - a review. Eur J Cancer. 2012;48:929–35.

    Article  CAS  Google Scholar 

  5. Klenova EM, Morse HC 3rd, Ohlsson R, Lobanenkov VV. The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin Cancer Biol. 2002;12:399–414.

    Article  CAS  Google Scholar 

  6. López-Romero R, Rodríguez-Esquivel M, Romero-Morelos P, García-Avilés JE, Serafín-Castillo A, Huerta-Padilla VM, et al. The expression of transcription factor BORIS and its association with the estrogen receptor beta (ER-β) in cervical carcinogenesis. Int J Clin Exp Pathol. 2019;12:3208–21.

    Google Scholar 

  7. Bui VM, Mettling C, Jou J, Sun HS. Genomic amplification of chromosome 20q13.33 is the early biomarker for the development of sporadic colorectal carcinoma. BMC Med Genomics. 2020;13:149.

    Article  CAS  Google Scholar 

  8. Shi H, Bevier M, Johansson R, Grzybowska E, Chen B, Eyfjörd JE, et al. Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome. Breast Cancer Res Treat. 2011;130:905–16.

    Article  CAS  Google Scholar 

  9. Tabach Y, Kogan-Sakin I, Buganim Y, Solomon H, Goldfinger N, Hovland R, et al. Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer. PLoS ONE. 2011;6:e14632.

    Article  CAS  Google Scholar 

  10. Rowley MJ, Corces VG. Organizational principles of 3D genome architecture. Nat Rev Genet. 2018;19:789–800.

    Article  CAS  Google Scholar 

  11. Lai AY, Fatemi M, Dhasarathy A, Malone C, Sobol SE, Geigerman C, et al. DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in B cell lymphomas. J Exp Med. 2010;207:1939–50.

    Article  CAS  Google Scholar 

  12. Witcher M, Emerson BM. Epigenetic silencing of the p16(INK4a) tumor suppressor is associated with loss of CTCF binding and a chromatin boundary. Mol Cell. 2009;34:271–84.

    Article  CAS  Google Scholar 

  13. Miyata K, Imai Y, Hori S, Nishio M, Loo TM, Okada R, et al. Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer. Proc Natl Acad Sci USA. 2021;118:e2025647118.

  14. Oreskovic E, Wheeler EC, Mengwasser KE, Fujimura E, Martin TD, Tothova Z, et al. Genetic analysis of cancer drivers reveals cohesin and CTCF as suppressors of PD-L1. Proc Natl Acad Sci USA. 2022;119:e2120540119.

  15. Hore TA, Deakin JE, Marshall, Graves JA. The evolution of epigenetic regulators CTCF and BORIS/CTCFL in amniotes. PLoS Genet. 2008;4:e1000169.

    Article  Google Scholar 

  16. Nishana M, Ha C, Rodriguez-Hernaez J, Ranjbaran A, Chio E, Nora EP, et al. Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation. Genome Biol. 2020;21:108.

    Article  CAS  Google Scholar 

  17. Pugacheva EM, Rivero-Hinojosa S, Espinoza CA, Méndez-Catalá CF, Kang S, Suzuki T, et al. Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions. Genome Biol. 2015;16:161.

    Article  Google Scholar 

  18. Rivero-Hinojosa S, Kang S, Lobanenkov VV, Zentner GE. Testis-specific transcriptional regulators selectively occupy BORIS-bound CTCF target regions in mouse male germ cells. Sci Rep. 2017;7:41279.

    Article  CAS  Google Scholar 

  19. Bergmaier P, Weth O, Dienstbach S, Boettger T, Galjart N, Mernberger M, et al. Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference. Nucleic Acids Res. 2018;46:7097–107.

    Article  CAS  Google Scholar 

  20. Lobanenkov VV, Zentner GE. Discovering a binary CTCF code with a little help from BORIS. Nucleus. 2018;9:33–41.

    Article  CAS  Google Scholar 

  21. Sleutels F, Soochit W, Bartkuhn M, Heath H, Dienstbach S, Bergmaier P, et al. The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner. Epigenetics Chromatin. 2012;5:8.

    Article  Google Scholar 

  22. Nora EP, Caccianini L, Fudenberg G, So K, Kameswaran V, Nagle A, et al. Molecular basis of CTCF binding polarity in genome folding. Nat Commun. 2020;11:5612.

    Article  CAS  Google Scholar 

  23. Pugacheva EM, Kubo N, Loukinov D, Tajmul M, Kang S, Kovalchuk AL, et al. CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention. Proc Natl Acad Sci USA. 2020;117:2020–31.

    Article  CAS  Google Scholar 

  24. Rivero-Hinojosa S, Pugacheva EM, Kang S, Méndez-Catalá CF, Kovalchuk AL, Strunnikov AV, et al. The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis. Nat Commun. 2021;12:3846.

    Article  CAS  Google Scholar 

  25. Balani S, Nguyen LV, Eaves CJ. Modeling the process of human tumorigenesis. Nat Commun. 2017;8:15422.

    Article  CAS  Google Scholar 

  26. Rao GK, Makani VKK, Mendonza JJ, Edathara PM, Patel N, Ramakrishna M, et al. Downregulation of BORIS/CTCFL leads to ROS-dependent cellular senescence and drug sensitivity in MYCN-amplified neuroblastoma. FEBS J. 2021;289:2915–34.

  27. Alberti L, Losi L, Leyvraz S, Benhattar J. Different effects of BORIS/CTCFL on stemness gene expression, sphere formation and cell survival in epithelial cancer stem cells. PLoS ONE. 2015;10:e0132977.

    Article  Google Scholar 

  28. Garikapati KR, Patel N, Makani VKK, Cilamkoti P, Bhadra U, Bhadra MP. Down-regulation of BORIS/CTCFL efficiently regulates cancer stemness and metastasis in MYCN amplified neuroblastoma cell line by modulating Wnt/β-catenin signaling pathway. Biochem Biophys Res Commun. 2017;484:93–9.

    Article  CAS  Google Scholar 

  29. Soltanian S, Dehghani H. BORIS: a key regulator of cancer stemness. Cancer Cell Int. 2018;18:154.

    Article  CAS  Google Scholar 

  30. Salgado-Albarrán M, Späth J, González-Barrios R, Baumbach J, Soto-Reyes E. CTCFL regulates the PI3K-Akt pathway and it is a target for personalized ovarian cancer therapy. NPJ Syst Biol Appl. 2022;8:5.

    Article  Google Scholar 

  31. Rahman M, Deleyrolle L, Vedam-Mai V, Azari H, Abd-El-Barr M, Reynolds BA. The cancer stem cell hypothesis: failures and pitfalls. Neurosurgery. 2011;68:531–45.

    Article  Google Scholar 

  32. Vicente-Duenas C, Romero-Camarero I, Cobaleda C, Sanchez-Garcia I. Function of oncogenes in cancer development: a changing paradigm. EMBO J. 2013;32:1502–13.

    Article  CAS  Google Scholar 

  33. Monk M, Hitchins M, Hawes S. Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development. Mol Hum Reprod. 2008;14:347–55.

    Article  CAS  Google Scholar 

  34. Yao H, Shao Q, Shao Y. Transcription factor CTCFL promotes cell proliferation, migration, and invasion in gastric cancer via activating DPPA2. Comput Math Methods Med. 2021;2021:9097931.

    Article  Google Scholar 

  35. Gretarsson KH, Hackett JA. Dppa2 and Dppa4 counteract de novo methylation to establish a permissive epigenome for development. Nat Struct Mol Biol. 2020;27:706–16.

    Article  CAS  Google Scholar 

  36. Alberti L, Renaud S, Losi L, Leyvraz S, Benhattar J. High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells. PLoS ONE. 2014;9:e109921.

    Article  Google Scholar 

  37. Liu Q, Chen K, Liu Z, Huang Y, Zhao R, Wei L, et al. BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells. Cancer Lett. 2017;403:165–74.

    Article  CAS  Google Scholar 

  38. Sun L, Huang L, Nguyen P, Bisht KS, Bar-Sela G, Ho AS, et al. DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer Res. 2008;68:2726–35.

    Article  CAS  Google Scholar 

  39. Nguyen P, Bar-Sela G, Sun L, Bisht KS, Cui H, Kohn E, et al. BAT3 and SET1A form a complex with CTCFL/BORIS to modulate H3K4 histone dimethylation and gene expression. Mol Cell Biol. 2008;28:6720–9.

    Article  CAS  Google Scholar 

  40. Zampieri M, Ciccarone F, Palermo R, Cialfi S, Passananti C, Chiaretti S, et al. The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells. Biochim Biophys Acta. 2014;1839:813–25.

    Article  CAS  Google Scholar 

  41. Pugacheva EM, Teplyakov E, Wu Q, Li J, Chen C, Meng C, et al. The cancer-associated CTCFL/BORIS protein targets multiple classes of genomic repeats, with a distinct binding and functional preference for humanoid-specific SVA transposable elements. Epigenetics Chromatin. 2016;9:35.

    Article  Google Scholar 

  42. Yoon SL, Kim DC, Cho SH, Lee SY, Chu IS, Heo J, et al. Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS. BMB Rep. 2010;43:698–703.

    Article  CAS  Google Scholar 

  43. Yoon SL, Roh YG, Lee SH, Kim SH, Kim MC, Kim SJ, et al. Analysis of promoter methylation and polymorphic minisatellites of BORIS and lack of association with gastric cancer. DNA Cell Biol. 2011;30:691–8.

    Article  CAS  Google Scholar 

  44. Yoon SL, Roh YG, Chu IS, Heo J, Kim SI, Chang H, et al. A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility. Exp Mol Med. 2016;48:e246.

    Article  CAS  Google Scholar 

  45. Kim TN, Kim WT, Jeong MS, Mun MH, Kim MH, Lee JZ, et al. Short rare minisatellite variant of BORIS-MS2 is related to bladder cancer susceptibility. Genes Genomics. 2019;41:249–56.

    Article  CAS  Google Scholar 

  46. Ramel C. Mini- and microsatellites. Environ Health Perspect. 1997;105:781–9.

    CAS  Google Scholar 

  47. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  Google Scholar 

  48. He J, Huang Y, Liu Z, Zhao R, Liu Q, Wei L, et al. Hypomethylation of BORIS is a promising prognostic biomarker in hepatocellular carcinoma. Gene. 2017;629:29–34.

    Article  CAS  Google Scholar 

  49. Gong M, Yan C, Jiang Y, Meng H, Feng M, Cheng W. Genome-wide bioinformatics analysis reveals CTCFL is upregulated in high-grade epithelial ovarian cancer. Oncol Lett. 2019;18:4030–9.

    CAS  Google Scholar 

  50. Makani VKK, Mendonza JJ, Edathara PM, Yerramsetty S, Pal Bhadra M. BORIS/CTCFL expression activates the TGFβ signaling cascade and induces Drp1 mediated mitochondrial fission in neuroblastoma. Free Radic Biol Med. 2021;176:62–72.

    Article  Google Scholar 

  51. Xiao K, Wang Y, Zhou L, Wang J, Wang Y, Tong, et al. Construction of ceRNA network to identify the lncRNA and mRNA related to non-small cell lung cancer. PLoS ONE. 2021;16:e0259091.

    Article  CAS  Google Scholar 

  52. Fiorentino FP, Macaluso M, Miranda F, Montanari M, Russo A, Bagella L, et al. CTCF and BORIS regulate Rb2/p130 gene transcription: a novel mechanism and a new paradigm for understanding the biology of lung cancer. Mol Cancer Res. 2011;9:225–33.

    Article  CAS  Google Scholar 

  53. Zhang Y, Fang M, Song Y, Ren J, Fang J, Wang X. Brother of regulator of imprinted sites (BORIS) suppresses apoptosis in colorectal cancer. Sci Rep. 2017;7:40786.

    Article  CAS  Google Scholar 

  54. Fang M, Song Y, Ren J, Yuan H, Fang J, Yan D, et al. Atractyloside mimics BORIS knockdown to induce DNA damage in colorectal cancer cells. Int J Clin Exp Pathol. 2018;11:3286–93.

    Google Scholar 

  55. Zhang Y, Song Y, Li C, Ren J, Fang M, Fang J, et al. Brother of regulator of imprinted sites inhibits cisplatin-induced DNA damage in non-small cell lung cancer. Oncol Lett. 2020;20:251.

    Article  Google Scholar 

  56. Renaud S, Loukinov D, Alberti L, Vostrov A, Kwon YW, Bosman FT, et al. BORIS/CTCFL-mediated transcriptional regulation of the hTERT telomerase gene in testicular and ovarian tumor cells. Nucleic Acids Res. 2011;39:862–73.

    Article  CAS  Google Scholar 

  57. Zhao R, Chen K, Zhou J, He J, Liu J, Guan P, et al. The prognostic role of BORIS and SOCS3 in human hepatocellular carcinoma. Medicine. 2017;96:e6420.

    Article  CAS  Google Scholar 

  58. He JY, Liu QY, Wei L, Liu ZJ, Huang Y, Yu XQ, et al. [BORIS regulates SOCS3 expression through epigenetic mechanisms in human hepatocellular carcinoma cells]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2018;49:1–7.

    Google Scholar 

  59. Hillman JC, Pugacheva EM, Barger CJ, Sribenja S, Rosario S, Albahrani M, et al. BORIS expression in ovarian cancer precursor cells alters the CTCF cistrome and enhances invasiveness through GALNT14. Mol Cancer Res. 2019;17:2051–62.

    Article  CAS  Google Scholar 

  60. Janssen SM, Moscona R, Elchebly M, Papadakis AI, Redpath M, Wang H, et al. BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cells. Cell Death Discov. 2020;6:1.

    Article  CAS  Google Scholar 

  61. Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30.

    Article  CAS  Google Scholar 

  62. Warburg O. On the origin of cancer cells. Science. 1956;123:309–14.

    Article  CAS  Google Scholar 

  63. Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016;41:211–8.

    Article  CAS  Google Scholar 

  64. Zahra K, Dey T, Ashish, Mishra SP, Pandey U. Pyruvate kinase M2 and cancer: the role of PKM2 in promoting tumorigenesis. Front Oncol. 2020;10:159.

    Article  Google Scholar 

  65. Méndez-Lucas A, Li X, Hu J, Che L, Song X, Jia J, et al. Glucose catabolism in liver tumors induced by c-MYC can be sustained by various PKM1/PKM2 ratios and pyruvate kinase activities. Cancer Res. 2017;77:4355–64.

    Article  Google Scholar 

  66. Singh S, Narayanan SP, Biswas K, Gupta A, Ahuja N, Yadav S, et al. Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect. Proc Natl Acad Sci USA. 2017;114:11440–5.

    Article  CAS  Google Scholar 

  67. Yadav S, Bhagat SD, Gupta A, Samaiya A, Srivastava A, Shukla S. Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer. BMC Cancer. 2019;19:1031.

    Article  Google Scholar 

  68. Debruyne DN, Dries R, Sengupta S, Seruggia D, Gao Y, Sharma B, et al. BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells. Nature. 2019;572:676–80.

    Article  CAS  Google Scholar 

  69. Resistance to ALK inhibitors in neuroblastoma is regulated by BORIS. Cancer Discov. 2019;9:1335.

  70. Herzig Y, Nevo S, Bornstein C, Brezis MR, Ben-Hur S, Shkedy A, et al. Transcriptional programs that control expression of the autoimmune regulator gene Aire. Nat Immunol. 2017;18:161–72.

    Article  CAS  Google Scholar 

  71. Hines WC, Bazarov AV, Mukhopadhyay R, Yaswen P. BORIS (CTCFL) is not expressed in most human breast cell lines and high grade breast carcinomas. PLoS ONE. 2010;5:e9738.

    Article  Google Scholar 

  72. Soltanian S, Dehghani H, Matin MM, Bahrami AR. Expression analysis of BORIS during pluripotent, differentiated, cancerous, and non-cancerous cell states. Acta Biochim Biophys Sin. 2014;46:647–58.

    Article  CAS  Google Scholar 

  73. Vanderstraeten A, Tuyaerts S, Everaert T, Van Bree R, Verbist G, Luyten C, et al. In vitro assessment of the expression and T cell immunogenicity of the tumor-associated antigens BORIS, MUC1, hTERT, MAGE-A3 and Sp17 in uterine cancer. Int J Mol Sci. 2016;17:1525.

  74. El-Sharkawy NM, Radwan WM, Essa ES, Kandeel EZ, Abd El-Fattah EK, Kandil SH, et al. Increased expression of brother of the regulator of imprinted sites in peripheral blood neutrophils is associated with both benign and malignant breast lesions. Cytom Part B Clin Cytom. 2017;92:355–60.

    Article  CAS  Google Scholar 

  75. Woloszynska-Read A, Zhang W, Yu J, Link PA, Mhawech-Fauceglia P, Collamat G, et al. Coordinated cancer germline antigen promoter and global DNA hypomethylation in ovarian cancer: association with the BORIS/CTCF expression ratio and advanced stage. Clin Cancer Res. 2011;17:2170–80.

    Article  CAS  Google Scholar 

  76. Okabayashi K, Fujita T, Miyazaki J, Okada T, Iwata T, Hirao N, et al. Cancer-testis antigen BORIS is a novel prognostic marker for patients with esophageal cancer. Cancer Sci. 2012;103:1617–24.

    Article  CAS  Google Scholar 

  77. Hoivik EA, Kusonmano K, Halle MK, Berg A, Wik E, Werner HM, et al. Hypomethylation of the CTCFL/BORIS promoter and aberrant expression during endometrial cancer progression suggests a role as an Epi-driver gene. Oncotarget. 2014;5:1052–61.

    Article  Google Scholar 

  78. Cheema Z, Hari-Gupta Y, Kita GX, Farrar D, Seddon I, Corr J, et al. Expression of the cancer-testis antigen BORIS correlates with prostate cancer. Prostate. 2014;74:164–76.

    Article  CAS  Google Scholar 

  79. Velázquez-Hernández N, Reyes-Romero MA, Barragán-Hernández M, Guerrero-Romero F, Rodríguez-Moran M, Aguilar-Durán M, et al. BORIS and CTCF are overexpressed in squamous intraepithelial lesions and cervical cancer. Genet Mol Res. 2015;14:6094–100.

    Article  Google Scholar 

  80. Vatolin S, Abdullaev Z, Pack SD, Flanagan PT, Custer M, Loukinov DI, et al. Conditional expression of the CTCF-paralogous transcriptional factor BORIS in normal cells results in demethylation and derepression of MAGE-A1 and reactivation of other cancer-testis genes. Cancer Res. 2005;65:7751–62.

    Article  CAS  Google Scholar 

  81. Smith IM, Glazer CA, Mithani SK, Ochs MF, Sun W, Bhan S, et al. Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer. PLoS ONE. 2009;4:e4961.

    Article  Google Scholar 

  82. Bhan S, Negi SS, Shao C, Glazer CA, Chuang A, Gaykalova DA, et al. BORIS binding to the promoters of cancer testis antigens, MAGEA2, MAGEA3, and MAGEA4, is associated with their transcriptional activation in lung cancer. Clin Cancer Res. 2011;17:4267–76.

    Article  CAS  Google Scholar 

  83. Zhao J, Wang Y, Liang Q, Xu Y, Sang J. MAGEA1 inhibits the expression of BORIS via increased promoter methylation. J Cell Sci. 2019;132:jcs218628.

  84. Schwarzenbach H, Eichelser C, Steinbach B, Tadewaldt J, Pantel K, Lobanenkov V, et al. Differential regulation of MAGE-A1 promoter activity by BORIS and Sp1, both interacting with the TATA binding protein. BMC Cancer. 2014;14:796.

    Article  Google Scholar 

  85. Kang Y, Hong JA, Chen GA, Nguyen DM, Schrump DS. Dynamic transcriptional regulatory complexes including BORIS, CTCF and Sp1 modulate NY-ESO-1 expression in lung cancer cells. Oncogene. 2007;26:4394–403.

    Article  CAS  Google Scholar 

  86. Hong JA, Kang Y, Abdullaev Z, Flanagan PT, Pack SD, Fischette MR, et al. Reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter coincides with derepression of this cancer-testis gene in lung cancer cells. Cancer Res. 2005;65:7763–74.

    Article  CAS  Google Scholar 

  87. Kosaka-Suzuki N, Suzuki T, Pugacheva EM, Vostrov AA, Morse HC 3rd, Loukinov D, et al. Transcription factor BORIS (Brother of the Regulator of Imprinted Sites) directly induces expression of a cancer-testis antigen, TSP50, through regulated binding of BORIS to the promoter. J Biol Chem. 2011;286:27378–88.

    Article  CAS  Google Scholar 

  88. Makovski A, Yaffe E, Shpungin S, Nir U. Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells. J Biol Chem. 2012;287:6100–12.

    Article  CAS  Google Scholar 

  89. Jones TA, Ogunkolade BW, Szary J, Aarum J, Mumin MA, Patel S, et al. Widespread expression of BORIS/CTCFL in normal and cancer cells. PLoS ONE. 2011;6:e22399.

    Article  CAS  Google Scholar 

  90. Renaud S, Pugacheva EM, Delgado MD, Braunschweig R, Abdullaev Z, Loukinov D, et al. Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors. Nucleic Acids Res. 2007;35:7372–88.

    Article  CAS  Google Scholar 

  91. Heller CG, Clermont Y. Spermatogenesis in man: an estimate of its duration. Science. 1963;140:184–6.

    Article  CAS  Google Scholar 

  92. Heller CH, Clermont Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res. 1964;20:545–75.

    CAS  Google Scholar 

  93. Misell LM, Holochwost D, Boban D, Santi N, Shefi S, Hellerstein MK, et al. A stable isotope-mass spectrometric method for measuring human spermatogenesis kinetics in vivo. J Urol. 2006;175:242–6.

    Article  CAS  Google Scholar 

  94. Neto FT, Bach PV, Najari BB, Li PS, Goldstein M. Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol. 2016;59:10–26.

    Article  Google Scholar 

  95. Wu X, Lu M, Yun D, Gao S, Chen S, Hu L, et al. Single-cell ATAC-Seq reveals cell type-specific transcriptional regulation and unique chromatin accessibility in human spermatogenesis. Hum Mol Genet. 2022;31:321–33.

    Article  CAS  Google Scholar 

  96. Suzuki T, Kosaka-Suzuki N, Pack S, Shin DM, Yoon J, Abdullaev Z, et al. Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS. Mol Cell Biol. 2010;30:2473–84.

    Article  CAS  Google Scholar 

  97. Rosa-Garrido M, Ceballos L, Alonso-Lecue P, Abraira C, Delgado MD, Gandarillas A. A cell cycle role for the epigenetic factor CTCF-L/BORIS. PLoS ONE. 2012;7:e39371.

    Article  CAS  Google Scholar 

  98. Nguyen P, Cui H, Bisht KS, Sun L, Patel K, Lee RS, et al. CTCFL/BORIS is a methylation-independent DNA-binding protein that preferentially binds to the paternal H19 differentially methylated region. Cancer Res. 2008;68:5546–51.

    Article  CAS  Google Scholar 

  99. Jelinic P, Stehle JC, Shaw P. The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation. PLoS Biol. 2006;4:e355.

    Article  Google Scholar 

  100. Poplinski A, Tüttelmann F, Kanber D, Horsthemke B, Gromoll J. Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2/H19 ICR1. Int J Androl. 2010;33:642–9.

    CAS  Google Scholar 

  101. Sati L, Zeiss C, Yekkala K, Demir R, McGrath J. Expression of the CTCFL gene during mouse embryogenesis causes growth retardation, postnatal lethality, and dysregulation of the transforming growth factor β pathway. Mol Cell Biol. 2015;35:3436–45.

    Article  CAS  Google Scholar 

  102. de Necochea-Campion R, Ghochikyan A, Josephs SF, Zacharias S, Woods E, Karimi-Busheri F, et al. Expression of the epigenetic factor BORIS (CTCFL) in the human genome. J Transl Med. 2011;9:213.

    Article  Google Scholar 

  103. Zambrano-Galván G, Reyes-Romero M, Bologna-Molina R, Almeda-Ojeda OE, Lemus-Rojero O. CTCFL (BORIS) mRNA expression in a peripheral giant cell granuloma of the oral cavity. Case Rep. Dent. 2014;2014:792615.

    Google Scholar 

  104. Schick B, Wemmert S, Willnecker V, Dlugaiczyk J, Nicolai P, Siwiec H, et al. Genome-wide copy number profiling using a 100K SNP array reveals novel disease-related genes BORIS and TSHZ1 in juvenile angiofibroma. Int J Oncol. 2011;39:1143–51.

    CAS  Google Scholar 

  105. Schultz B, Yao X, Deng Y, Waner M, Spock C, Tom L, et al. A common polymorphism within the IGF2 imprinting control region is associated with parent of origin specific effects in infantile hemangiomas. PLoS ONE. 2015;10:e0113168.

    Article  Google Scholar 

  106. D’Angelo R, Marini V, Rinaldi C, Origone P, Dorcaratto A, Avolio M, et al. Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation. Brain Pathol. 2011;21:215–24.

    Article  Google Scholar 

  107. Sati L, Soygur B, Goksu E, Bassorgun CI, McGrath J. CTCFL expression is associated with cerebral vascular abnormalities. Tissue Cell. 2021;72:101528.

    Article  CAS  Google Scholar 

  108. Hernandez-Gonzalez I, Tenorio-Castano J, Ochoa-Parra N, Gallego N, Pérez-Olivares C, Lago-Docampo M, et al. Novel genetic and molecular pathways in pulmonary arterial hypertension associated with connective tissue disease. Cells. 2021;10:1488.

  109. Novak Kujundžić R, Grbeša I, Ivkić M, Krušlin B, Konjevoda P, Gall Trošelj K. Possible prognostic value of BORIS transcript variants ratio in laryngeal squamous cell carcinomas - a pilot study. Pathol Oncol Res. 2014;20:687–95.

    Article  Google Scholar 

  110. Joosse SA, Müller V, Steinbach B, Pantel K, Schwarzenbach H. Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases. Br J Cancer. 2014;111:909–17.

    Article  CAS  Google Scholar 

  111. Li X, Ning L, Zhang Q, Ge Y, Liu C, Bi S, et al. Expression profile of ACTL8, CTCFL, OIP5 and XAGE3 in glioma and their prognostic significance: a retrospective clinical study. Am J Transl Res. 2020;12:7782–96.

    CAS  Google Scholar 

  112. Chen K, Huang W, Huang B, Wei Y, Li B, Ge Y, et al. BORIS, brother of the regulator of imprinted sites, is aberrantly expressed in hepatocellular carcinoma. Genet Test Mol Biomark. 2013;17:160–5.

    Article  CAS  Google Scholar 

  113. Salgado-Albarrán M, González-Barrios R, Guerra-Calderas L, Alcaraz N, Estefanía Sánchez-Correa T, Castro-Hernández C, et al. The epigenetic factor BORIS (CTCFL) controls the androgen receptor regulatory network in ovarian cancer. Oncogenesis. 2019;8:41.

    Article  Google Scholar 

  114. Asano T, Hirohashi Y, Torigoe T, Mariya T, Horibe R, Kuroda T, et al. Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy. Oncotarget. 2016;7:11223–37.

    Article  Google Scholar 

  115. Horibe R, Hirohashi Y, Asano T, Mariya T, Suzuki T, Takaya A, et al. Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is a novel target of lung cancer stem-like cell immunotherapy. PLoS ONE. 2017;12:e0171460.

    Article  Google Scholar 

  116. D’Arcy V, Abdullaev ZK, Pore N, Docquier F, Torrano V, Chernukhin I, et al. The potential of BORIS detected in the leukocytes of breast cancer patients as an early marker of tumorigenesis. Clin Cancer Res. 2006;12:5978–86.

    Article  Google Scholar 

  117. Mkrtichyan M, Ghochikyan A, Davtyan H, Movsesyan N, Loukinov D, Lobanenkov V, et al. Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. Cell Immunol. 2011;270:188–97.

    Article  CAS  Google Scholar 

  118. Loukinov D, Ghochikyan A, Mkrtichyan M, Ichim TE, Lobanenkov VV, Cribbs DH, et al. Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. J Cell Biochem. 2006;98:1037–43.

    Article  CAS  Google Scholar 

  119. Ghochikyan A, Mkrtichyan M, Loukinov D, Mamikonyan G, Pack SD, Movsesyan N, et al. Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer-testis antigen, brother of the regulator of imprinted sites. J Immunol. 2007;178:566–73.

    Article  CAS  Google Scholar 

  120. Mkrtichyan M, Ghochikyan A, Loukinov D, Davtyan H, Ichim TE, Cribbs DH, et al. DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolonsignificantly inhibits tumor growth and prolongs the survival of mice. Gene Ther. 2008;15:61–4.

    Article  CAS  Google Scholar 

  121. Dougherty CJ, Ichim TE, Liu L, Reznik G, Min WP, Ghochikyan A, et al. Selective apoptosis of breast cancer cells by siRNA targeting of BORIS. Biochem Biophys Res Commun. 2008;370:109–12.

    Article  CAS  Google Scholar 

  122. Mahdevar E, Safavi A, Abiri A, Kefayat A, Hejazi SH, Miresmaeili SM, et al. Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches. J Biomol Struct Dyn. 2022;40:6363–80.

  123. Mahdevar E, Kefayat A, Safavi A, Behnia A, Hejazi SH, Javid A, et al. Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer-testis antigen target in a murine mammary carcinoma model. Sci Rep. 2021;11:23121.

    Article  CAS  Google Scholar 

  124. Xu H, Fang M, Li C, Zuo B, Ren J, Zhang Y. BORIS-mediated generation of circular RNAs induces inflammation. Transl Oncol. 2022;18:101363.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 71673193) and the Key research and development project of the science and technology department of Sichuan Province (2021YFS0106).

Author information

Author notes

  1. These authors contributed equally: Siqi Zhou, Lian Li.

Authors and Affiliations

  1. Department of Liver Surgery, West China Hospital, Sichuan University Medical School, 37 Guo Xue Road, Chengdu, 610041, Sichuan Province, China

    Siqi Zhou, Lian Li, Ming Zhang & Bo Li

  2. Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, Sichuan Province, China

    Yang Qin

Authors
  1. Siqi Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SZ and LL drafted and revised the manuscript. MZ helped revise the manuscript. YQ and BL guided the whole work and approved the final version.

Corresponding authors

Correspondence to Yang Qin or Bo Li.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, S., Li, L., Zhang, M. et al. The function of brother of the regulator of imprinted sites in cancer development. Cancer Gene Ther 30, 236–244 (2023). https://doi.org/10.1038/s41417-022-00556-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-022-00556-0

  • Springer Nature America, Inc.

Search

Navigation