Document Type : Original Article

Authors

Department of Biotechnology, PSG College of Technology, Coimbatore-641004, Tamil Nadu, India

Abstract

Background: The transcription factor twist-related protein 1 (TWIST1) plays a major role in the prognosis of breast cancer. Our present study aimed to identify the network of TWIST1 with related oncogenes and their associated miRNAs.
Method: This in silico study included the differential expression analysis of genes and miRNA associated with breast carcinoma. The breast cancer patients’ data were retrieved from the Gene Expression Omnibus database and the differential expression analysis was done using GEO2R. Transfac analysis was performed to determine the binding sites of TWIST1. We predicted the target genes of MicroRNA-96 (miR-96) using miRBase. An integrated network was generated among TWIST1 and target genes of miR-96 through Gene MANIA. Survival analysis was carried out for TWIST1 using UALCAN. Experimental methods, including gene expression analysis, were performed in the MDA-MB-231 cell line for validating in silico findings.
Results: miR-96, the second differentially expressed miRNA among the top 250 miRNAs, was found to have eight binding sites for TWIST1. TWIST1 was observed to be significantly correlated with patient prognosis. ACTN4, BCL2, and FRMD4A were upregulated and CAMTA1, DAB2IP, and E- Cadherin were downregulated in the expression studies carried out in the MDA-MB-231 breast cancer cell line.
Conclusion: A network between TWIST1 and target genes of miR-96 was analyzed. Hence, targeting the genes linked with miR-96 could work toward an efficient therapeutic option for breast cancer metastasis.

Keywords

How to cite this article:

Manoharan JP, Karunakaran KN, Dasarathan G, Vidyalakshmi S. Probing into the network of transcription factor twist-related protein 1 (TWIST1) in breast cancer metastasis. Middle East J Cancer. 2023;14(1):49-60. doi: 10.30476/ mejc.2022.90289.1569.

  1. Lin A, Rugo HS. The role of trastuzumab in early stage breast cancer: current data and treatment recommendations. Curr Treat Options Oncol. 2007;8(1): 47-60. doi: 10.1007/s11864-007-0008-2.
  2. McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer -epidemiology, risk factors, and genetics. BMJ. 2000;321(7261):624-8. doi: 10.1136/bmj.321.7261.624.
  3. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783-92. doi: 10.1056/NEJM200 103153441101.
  4. Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005;353(16):1734-6. doi: 10.1056/NEJMe058196.
  5. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666-76. doi: 10.1056/ NEJMoa072113.
  6. Leary AF, Sirohi B, Johnston SR. Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer. Breast Cancer Res. 2007;9(5):112. doi: 10.1186/bcr1763.
  7. Lambert M, Jambon S, Depauw S, David-Cordonnier MH. Targeting transcription factors for cancer treatment. Molecules. 2018;23(6):1479. doi: 10.3390/molecules23061479.
  8. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117(7):927-39. doi: 10.1016/j. cell.2004.06.006.
  9. Wang X, Ling MT, Guan XY, Tsao SW, Cheung HW, Lee DT, et al. Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells. Oncogene. 2004;23(2):474-82. doi: 10.1038/sj.onc. 1207128.
  10. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102-14. doi: 10.1038/nrg2290.
  11. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-97. doi: 10.1016/s0092-8674(04)00045-5.
  12. Cheng AM, Byrom MW, Shelton J, Ford LP. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res. 2005;33(4):1290-7. doi: 10.1093/ nar/gki200.
  13. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682-8. doi: 10.1038/nature06174. Erratum in: Nature. 2008;455 (7210):256.
  14. Yu X, Lin J, Zack DJ, Mendell JT, Qian J. Analysis of regulatory network topology reveals functionally distinct classes of microRNAs. Nucleic Acids Res. 2008;36(20):6494-503. doi: 10.1093/nar/gkn712.
  15. Fendler A, Jung M, Stephan C, Erbersdobler A, Jung K, Yousef GM. The antiapoptotic function of miR-96 in prostate cancer by inhibition of FOXO1. PLoS One. 2013;8(11):e80807. doi: 10.1371/journal.pone. 0080807.
  16. Liang H, Li WH. MicroRNA regulation of human protein protein interaction network. RNA. 2007;13(9):1402-8. doi: 10.1261/rna.634607.
  17. Lin CC, Chen YJ, Chen CY, Oyang YJ, Juan HF, Huang HC. Crosstalk between transcription factors and microRNAs in human protein interaction network. BMC Syst Biol. 2012;6:18. doi: 10.1186/1752-0509- 6-18.
  18. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013;41(Database issue): D991-5. doi: 10.1093/nar/gks1193.
  19. Fan Y, Siklenka K, Arora SK, Ribeiro P, Kimmins S, Xia J. miRNet - dissecting miRNA-target interactions and functional associations through network-based visual analysis. Nucleic Acids Res. 2016;44(W1): W135-41. doi: 10.1093/nar/gkw288.
  20. Huang HY, Lin YC, Li J, Huang KY, Shrestha S, Hong HC, et al. miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. Nucleic Acids Res. 2020;48(D1):D148-D154. doi: 10.1093/nar/gkz896.
  21. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(Web Server issue):W214-20. doi: 10.1093/nar/gkq537.
  22. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649-58. doi: 10.1016/j.neo. 2017.05.002.
  23. Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439-46. doi: 10.1007/s10549-016- 4013-7.
  24. Gilbert JR, Vance JM. Isolation of genomic DNA from mammalian cells. Curr Protoc Hum Genet. 2001; Appendix 3:Appendix 3B. doi: 10.1002/04711 42905.hga03bs19.
  25. Callagy GM, Pharoah PD, Pinder SE, Hsu FD, Nielsen TO, Ragaz J, et al. BCL-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res. 2006;12(8):2468- 75. doi: 10.1158/1078-0432.CCR-05-2719. Erratum in: Clin Cancer Res. 2006;12(16):5002.
  26. Xie W, Sun F, Chen L, Cao X. miR-96 promotes breast cancer metastasis by suppressing MTSS1. Oncol Lett. 2018;15(3):3464-71. doi: 10.3892/ol.2018.7728.
  27. Anderson O, Guttilla Reed IK. Regulation of cell growth and migration by miR-96 and miR-183 in a breast cancer model of epithelial-mesenchymal transition. PLoS One. 2020; 15(5): e0233187. doi: 10.1371/journal.pone.0233187.
  28. Lin Y, Liu AY, Fan C, Zheng H, Li Y, Zhang C, et al. MicroRNA-33b inhibits breast cancer metastasis by targeting HMGA2, SALL4 and TWIST1. Sci Rep. 2015;5:9995. doi: 10.1038/srep09995.
  29. Yeh TC, Huang TT, Yeh TS, Chen YR, Hsu KW, Yin PH, et al. miR-151-3p targets TWIST1 to repress migration of human breast cancer cells. PLoS One. 2016;11(12):e0168171. doi: 10.1371/journal.pone. 0168171.
  30. Hsu KS, Kao HY. Alpha-actinin 4 and tumorigenesis of breast cancer. Vitam Horm. 2013;93:323-51. doi: 10.1016/B978-0-12-416673-8.00005-8.
  31. Callagy GM, Webber MJ, Pharoah PD, Caldas C. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer. BMC Cancer. 2008;8:153. doi: 10.1186/1471-2407-8-153.
  32. Goldie SJ, Mulder KW, Tan DW, Lyons SK, Sims AH, Watt FM. FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis. Cancer Res. 2012;72(13):3424-36. doi: 10.1158/0008- 5472.CAN-12-0423.
  33. Katoh M, Katoh M. Identification and characterization of FLJ10737 and CAMTA1 genes on the commonly deleted region of neuroblastoma at human chromosome 1p36.31-p36.23. Int J Oncol. 2003;23(4):1219-24.
  34. Liu L, Xu C, Hsieh JT, Gong J, Xie D. DAB2IP in cancer. Oncotarget. 2016;7(4):3766-76. doi: 10.18632/ oncotarget.6501.
  35. Oda H, Tsukita S, Takeichi M. Dynamic behavior of the cadherin-based cell-cell adhesion system during Drosophila gastrulation. Dev Biol. 1998;203(2):435- 50. doi: 10.1006/dbio.1998.9047.
  36. Xu Y, Qin L, Sun T, Wu H, He T, Yang Z, et al. TWIST1 promotes breast cancer invasion and metastasis by silencing Foxa1 expression. Oncogene. 2017;36(8): 1157-66. doi: 10.1038/onc.2016.286.
  37. Xu Y, Lee DK, Feng Z, Xu Y, Bu W, Li Y, et al. Breast tumor cell-specific knockout of TWIST1 inhibits cancer cell plasticity, dissemination, and lung metastasis in mice. Proc Natl Acad Sci U S A. 2017;114(43):11494- 9. doi: 10.1073/pnas.1618091114.