WRAP53 Polymorphism, rs2287498: A Case Study in Northwest of Iran?

Document Type: Original Article

Authors

1 Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran

2 Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran and Department of Molecular Biology and Cancer Research, Azarbaijan Shahid Madani University, Tabriz, Iran

Abstract

Background: Non-coding RNAs apply regulations on expression or function of a gene. A class of non-coding RNAs, natural antisense transcripts, might overlap with their flanking genes and emerge a new complexity upon regulation. WRAP53, is a natural antisense transcript overlapped in a head-to-head manner on the opposite strand of TP53. It has 3 transcripts of which WRAP53β produces a protein and is needed for RNP biogenesis. Single nucleotide polymorphisms in this gene are associated with cancer susceptibility.
Methods: In this study, we investigated the impact of WRAP53 Ex2+19 C>T polymorphism (rs2287498) in breast cancer susceptibility in Iranian-Azeri women, by tetra-primer amplification-refractory mutation system-polymerase chain reaction (tetra-ARMS PCR) method, in 222 patients women with breast cancer. We analyzed our data using javastat statistics package (http://statpages.org/ctab2x2.html) online software for allele and genotype frequencies and SPSS v.24 for evaluating rs2287498 association with clinicopathological features. Also, in silico experiments were carried out for predicting the second RNA structure with mfold v3.6, and for prediction of amino acid substitution effect with online software polyphen2.
Results: Our results show a statistical significance of tumor size with the risk of breast cancer (p-value=0.036) but no significant genotype frequencies of rs2297498 and clinicopathological features with breast cancer susceptibility. in silico analysis estimated no significant changes in RNA or protein for this polymorphism.
Conclusion: In conclusion, these findings suggest no relationship between rs2287498 and breast cancer susceptibility except with tumor size which confers a possible implication as a prognostic marker in relation to the size of the tumor.

Keywords


  1. Grossi E, Sánchez Y, Huarte M. Expanding the p53 regulatory network: LncRNAs take up the challenge. Biochim Biophys Acta 2016; 1859(1):200-8.
  2. Latgé G, Poulet C, Bours V, Josse C, Jerusalem G. Natural antisense transcripts: molecular mechanisms and implications in breast cancers. Int J Mol Sci 2018; 19(1):E123.
  3. Ning Q, Li Y, Wang Z, Zhou S, Sun Hc, Yu G. The evolution and expression pattern of human overlapping lncrna and protein-coding gene pairs. Scientific Reports 2017; 7:42775.
  4. Khorkova O, Myers AJ, Hsiao J, Wahlestedt C. Natural antisense transcripts. Human Molecular Genetics 2014; 23(R1):R54-63.
  5. Saldaña-Meyer R, Recillas-Targa F. Transcriptional and epigenetic regulation of the p53 tumor suppressor gene. Epigenetics 2011; 6(9):1068-77.
  6. Polson A, Reisman D. The bidirectional p53-Wrap53 beta promoter is controlled by common cis- and trans-regulatory elements. Gene 2014; 538(1):138-49.
  7. Pouladi N, Kouhsari SM, Feizi MH, Gavgani RR, Azarfam P. Overlapping region of p53/wrap53 transcripts: mutational analysis and sequence similarity with microRNA-4732-5p. Asian Pac J Cancer Prev 2013; 14(6):3503-7.
  8. Henriksson S, Farnebo M. On the road with WRAP53 beta: guardian of Cajal bodies and genome integrity. Front Genet 2015; 6:91.
  9. Mahmoudi S, Henriksson S, Corcoran M, Méndez-Vidal C, Wiman KG, Farnebo M. Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage. Mol Cell 2009; 33(4):462-71.
  10. Enwerem II, Velma V, Broome HJ, Kuna M, Begum RA, Hebert MD. Coilin association with Box C/D scaRNA suggests a direct role for the Cajal body marker protein in scaRNP biogenesis. Biol Open 2014; 3(4):240-9.
  11. Tomlinson RL, Li J, Culp BR, Terns RM, Terns MP. A Cajal body-independent pathway for telomerase trafficking in mice. Exp Cell Res 2010; 316(17):2797-809.
  12. Richard P, Darzacq X, Bertrand E, Jády BE, Verheggen C, Kiss T. A common sequence motif determines the Cajal body‐specific localization of box H/ACA scaRNAs. EMBO J 2003; 22(16):4283-93.
  13. Tycowski KT, Shu MD, Kukoyi A, Steitz JA. A conserved WD40 protein binds the cajal body localization signal of scaRNP particles. Mol Cell 2009; 34(1):47-57.
  14. Stern JL, Zyner KG, Pickett HA, Cohen SB, Bryan TM. Telomerase recruitment requires both TCAB1 and Cajal bodies independently. Mol Cell Biol 2012; 32(13):2384-95.
  15. Yuan JM, Li XD, Liu ZY, Hou GQ, Kang JH, Huang DY, et al. Cisplatin induces apoptosis via upregulating Wrap53 in U-2OS osteosarcoma cells. Asian Pac J Cancer Prev 2011; 12(12):3465-9.
  16. Hedström E, Pederiva C, Farnebo J, Nodin B, Jirström K, Brennan DJ, et al. Downregulation of the cancer susceptibility protein WRAP53β in epithelial ovarian cancer leads to defective DNA repair and poor clinical outcome. Cell Death and Disease 2015; 6(10):e1892.
  17. Rassoolzadeh H, Böhm S, Hedström E, Gad H, Helleday T, Henriksson S, et al. Overexpression of the scaffold WD40 protein WRAP53β enhances the repair of and cell survival from DNA double-strand breaks. Cell Death Dis 2016; 7:e2267.
  18. Henriksson S, Rassoolzadeh H, Hedström E, Coucoravas C, Julner A, Goldstein M, et al. The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair. Genes Dev 2014; 28(24):2726-38.
  19. Wang K, Ge Y, Ni C, Cui B, Du J, Zhang B, et al. Epstein-Barr virus-induced up-regulation of TCAB1 is involved in the DNA damage response in nasopharyngeal carcinoma. Sci Rep 2017; 7(1):3218.
  20. Sun Y, Cao L, Sheng X, Chen J, Zhou Y, Yang C, et al. WDR79 promotes the proliferation of non-small cell lung cancer cells via USP7-mediated regulation of the Mdm2-p53 pathway. Cell Death Dis 2017; 8(4):e2743.
  21. Yuan XS, Cao LX, Hu YJ, Bao FC, Wang ZT, Cao JL, et al. Clinical, cellular, and bioinformatic analyses reveal involvement of WRAP53 overexpression in carcinogenesis of lung adenocarcinoma. Tumour Biol 2017; 39(3):1010428317694309.
  22. Rao X, Huang D, Sui X, Liu G, Song X, Xie J, et al. Overexpression of WRAP53 is associated with development and progression of esophageal squamous cell carcinoma. PLoS One 2014; 9(3):e91670.
  23. Sun CK, Luo XB, Gou YP, Hu L, Wang K, Li C, et al. TCAB1: a potential target for diagnosis and therapy of head and neck carcinomas. Mol Cancer 2014; 13:180.
  24. Zhong F, Savage SA, Shkreli M, Giri N, Jessop L, Myers T, et al. Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita. Genes Dev 2011; 25(1):11-6.
  25. Rosner B. Fundamentals of Biostatistics 2006 [ 6th Ed:[Available from: https://statpages.info/ctab2x2.html.
  26. Vang VO. Significance of WRAP53 in breast cancer: mutation analyses and gene expression studies [dissertation]. Oslo: Akershus University College; 2012.
  27. Sedaie Bonab A, Pouladi N, Hosseinpourfeizi MA, Ravanbakhsh Gavgani R, Dehghan R, Azarfam P, et al. Single-strand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population. Med Oncol 2014; 31(9):168.
  28. Silwal-Pandit L, Russnes H, Borgen E, Skarpeteig V, Moen Vollan HK, Schlichting E, et al. The Sub-Cellular Localization of WRAP53 Has Prognostic Impact in Breast Cancer. PLoS One 2015; 10(10):e0139965.
  29. Lv Y, Jia C, Jiang A, Zhang H, Wang Y, Liu F, et al. Analysis of association between MGMT and p53 gene single nucleotide polymorphisms and laryngeal cancer. Anticancer Res 2017; 37(8): 4399-403.
  30. Huang C, Liu W, Ji GX, Gu AH, Qu JH, Song L, et al. Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population. Asian J Androl 2012; 14(5):691-4.
  31. Mędrek K, Magnowski P, Masojć B, Chudecka-Głaz A, Torbe B, Menkiszak J, et al. Association of common WRAP 53 variant with ovarian cancer risk in the Polish population. Mol Biol Rep 2013; 40(3):2145-7.
  32. Garcia-Closas M, Kristensen V, Langerød A, Qi Y, Yeager M, Burdett L, et al. Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer. Int J Cancer 2007; 121(11):2532-8.