3D And 2D RNA Structure Prediction Of The BRCA2 Gene And Its Silencing RNA In The Breast Cancer

Ryan Wijaya  -  Department of Bioinformatics School of Life Sciences Indonesia International Institute for Life Sciences, Indonesia
Arli Aditya Parikesit*    -  Department of Bioinformatics School of Life Sciences Indonesia International Institute for Life Sciences, Indonesia
Rizky Nurdiansyah  -  Department of Bioinformatics School of Life Sciences Indonesia International Institute for Life Sciences, Indonesia

(*) Corresponding Author

Supp. File(s): common.other

Breast cancer is one of the most threatening diseases for women. It is found that BRCA2 gene plays a significant role in breast cancer, provided that mutations occurred. The objective of this study is to determine whether the bioinformatics approach could provide the gene networking, molecular simulation, and computational metabolomics information to shed the relation between BRCA2 gene mutation with breast cancer progression. The methods are utilizing molecular simulation tools to comprehend the biochemical interaction of BRCA2 gene with other oncogenic genes. Lastly, the molecular docking tool is devised to provide the molecular interactions information. It could be implied that the Computer-Aided Drug Design (CADD)-based in silico transcriptomics tools could provide the fine-grained information on the exact role of BRCA2 gene in the progression of breast cancer. The clinical impact of this study could only be measured after the wet laboratory experiment is conducted to validate the computational approach results

Supplement Files

Keywords : BRCA; Bioinformatics; Breast Cancer; Molecular Simulation; Gene Networking

  1. Anurogo, D., Parikesit, A.A., Ikrar, T., 2019. LncRNAs in CONDBITs Perspectives, From Genetics towards Theranostics. J. Sains Kesihat. Malaysia 17, 1–16. https://doi.org/10.17576/jskm-2019-1702-01
  2. Arifin, M.Z., Agustriawan, D., Parikesit, A.A.P., 2020. Molecular simulation oF MDM2 and E6AP proteins as P53 regulator in cervical cancer. Biointerface Res. Appl. Chem. 10, 5875–5879. https://doi.org/10.33263/BRIAC104.875879
  3. Bonofiglio, D., Giordano, C., De Amicis, F., Lanzino, M., Andò, S., 2016. Natural Products as Promising Antitumoral Agents in Breast Cancer: Mechanisms of Action and Molecular Targets. Mini-Reviews Med. Chem. 16, 596–604. https://doi.org/10.2174/1389557515666150709110959
  4. Burnett, J.C., Rossi, J.J., 2012. RNA-based therapeutics: current progress and future prospects. Chem. Biol. 19, 60–71. https://doi.org/10.1016/j.chembiol.2011.12.008
  5. Cherigo, L., Lopez, D., Martinez-Luis, S., 2015. Marine natural products as breast cancer resistance protein inhibitors. Mar. Drugs. https://doi.org/10.3390/md13042010
  6. Cleator, S., Heller, W., Coombes, R.C., 2007. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 8, 235–244. https://doi.org/10.1016/S1470-2045(07)70074-8
  7. Davis, B.K., 1998. The forces driving molecular evolution. Prog. Biophys. Mol. Biol. 69, 83–150. https://doi.org/10.1016/S0079-6107(97)00034-5
  8. Eigen, M., McCaskill, J., Schuster, P., 1988. Molecular quasi-species. J. Phys. Chem. 92, 6881–6891. https://doi.org/10.1021/j100335a010
  9. Flamm, C., Hofacker, I.L., Stadler, P.F., Wolfinger, T., Wolfinger, M.T., 2002. Barrier Trees of Degenerate Landscapes. Zeitschrift für Phys. Chemie 216, 155. https://doi.org/10.1524/zpch.2002.216.2.155
  10. Goncalves, R., Warner, W.A., Luo, J., Ellis, M.J., 2014. New concepts in breast cancer genomics and genetics. Breast Cancer Res. https://doi.org/10.1186/s13058-014-0460-4
  11. Gruber, A.R., Lorenz, R., Bernhart, S.H., Neuböck, R., Hofacker, I.L., 2008. The Vienna RNA websuite. Nucleic Acids Res. 36. https://doi.org/10.1093/nar/gkn188
  12. Hashem, Y., Auffinger, P., 2009. A short guide for molecular dynamics simulations of RNA systems. Methods 47, 187–197. https://doi.org/10.1016/j.ymeth.2008.09.020
  13. Hedau, S., Batra, M., Singh, U., Bharti, A., Ray, A., Das, B., 2015. Expression of BRCA1 and BRCA2 proteins and their correlation with clinical staging in breast cancer. J. Cancer Res. Ther. https://doi.org/10.4103/0973-1482.140985
  14. Kozakov, D., Hall, D.R., Xia, B., Porter, K.A., Padhorny, D., Yueh, C., Beglov, D., Vajda, S., 2017. The ClusPro web server for protein-protein docking. Nat. Protoc. https://doi.org/10.1038/nprot.2016.169
  15. Lorenz, R., Bernhart, S.H., Höner zu Siederdissen, C., Tafer, H., Flamm, C., Stadler, P.F., Hofacker, I.L., 2011. ViennaRNA Package 2.0. Algorithms Mol. Biol. 6, 26. https://doi.org/10.1186/1748-7188-6-26
  16. McDowell, S.E., Spacková, N., Sponer, J., Walter, N.G., 2007. Molecular dynamics simulations of RNA: an in silico single molecule approach. Biopolymers 85, 169–84. https://doi.org/10.1002/bip.20620
  17. Parikesit, A.A., 2018. The Construction of Two and Three Dimensional Molecular Models for the miR-31 and Its Silencer as the Triple Negative Breast Cancer Biomarkers. Online J. Biol. Sci. 18, 424–431. https://doi.org/10.3844/ojbsci.2018.424.431
  18. Parikesit, A.A., Agustriawan, D., Nurdiansyah, R., 2020. Protein Annotation of Breast-cancer-related Proteins with Machine-learning Tools. Makara J. Sci. 24, 6. https://doi.org/10.7454/mss.v24i1.12106
  19. Parikesit, A.A., Agustriawan, D., Nurdiansyah, R., 2018a. Telaah Sistematis Diagnosis dan Pengobatan Kanker Payudara Berbasis Transkriptomik, in: PROSIDING SEMINAR NASIONAL BIOLOGI 2018. FMIPA UNESA, Surabaya, pp. 438–443.
  20. Parikesit, A.A., Utomo, D.H., Karimah, N., 2018b. Determination of secondary and tertiary structures of cervical cancer lncRNA diagnostic and siRNA therapeutic biomarkers. Indones. J. Biotechnol. 23, 1. https://doi.org/10.22146/ijbiotech.28508
  21. Peshkin, B.N., Alabek, M.L., Isaacs, C., 2010. BRCA1/2 mutations and triple negative breast cancers. Breast Dis. 32, 25–33. https://doi.org/10.3233/BD-2010-0306
  22. Petrovic, N., Davidovic, R., Bajic, V., Obradovic, M., Isenovic, R.E., 2017. MicroRNA in breast cancer: The association with BRCA1/2. Cancer Biomarkers. https://doi.org/10.3233/CBM-160319
  23. Rother, M., Milanowska, K., Puton, T., Jeleniewicz, J., Rother, K., Bujnicki, J.M., 2011. ModeRNA server: an online tool for modeling RNA 3D structures. Bioinformatics 27, 2441–2442. https://doi.org/10.1093/bioinformatics/btr400
  24. Spicer, J., 2005. Technology evaluation: nimotuzumab, the Center of Molecular Immunology/YM BioSciences/Oncoscience. Curr. Opin. Mol. Ther. 7, 182–91.
  25. Šponer, J., Bussi, G., Krepl, M., Banáš, P., Bottaro, S., Cunha, R.A., Gil-Ley, A., Pinamonti, G., Poblete, S., Jurečka, P., Walter, N.G., Otyepka, M., 2018. RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview. Chem. Rev. 118, 4177–4338. https://doi.org/10.1021/acs.chemrev.7b00427
  26. Surveillance Epidemiology and End Results Program, 2019. Cancer Stat Facts: Female Breast Cancer. Natl. Cancer Inst. 1–10.
  27. Tafer, H., Ameres, S.L., Obernosterer, G., Gebeshuber, C.A., Schroeder, R., Martinez, J., Hofacker, I.L., 2008. The impact of target site accessibility on the design of effective siRNAs. Nat. Biotechnol. 26, 578–83. https://doi.org/10.1038/nbt1404
  28. TBI, 2016. Vienna RNA Package Web Version 2.0 [WWW Document]. URL http://rna.tbi.univie.ac.at/#intro
  29. Valeska, M.D., Adisurja, G.P., Bernard, S., Wijaya, R., Aldino, M., Parikesit, A.A., 2019. The Role of Bioinformatics in Personalized Medicine: Your Future Medical Treatment. Cermin Dunia Kedokt. 46, 785–788.
  30. Wheeler, N.J., Agbedanu, P.N., Kimber, M.J., Ribeiro, Paula, Day, T.A., Zamanian, M., Werf, M., Vlas, S., Brooker, S., Looman, C., Nagelkerke, N., Habbema, J., Engels, D., Murray, C., Vos, T., Lozano, R., Naghavi, M., Flaxman, A., Michaud, C., Wang, W., Wang, L., Liang, Y.-S., Gilbert, I., Chen, B., Wen, J.-F., Scimone, M., Kravarik, K., Lapan, S., Reddien, P, Zhang, J., Yuan, Z., Zheng, M., Sun, Y., Wang, Y., Yang, S., Evans, D., Owlarn, S., Romero, B.T., Chen, C., Aboobaker, A., Reddien, PW, Bermange, A., Murfitt, K., Jennings, J., Alvarado, A.S., Collins, J., Hou, X., Romanova, E., Lambrus, B., Miller, C., Saberi, A., Sweedler, J., Newmark, P, Gilleard, J., Robb, S., Ross, E., Sa, A., Abril, J., Cebri’a, F., Rodrıguez-Esteban, G., Horn, T., Fraguas, S., Calvo, B., Bartscherer, K., Sal’o, E., Galloni, M., Resch, A., Palakodeti, D., Lu, Y.-C., Horowitz, M., Graveley, B., Solana, J., Kao, D., Mihaylova, Y., Jaber-Hijazi, F., Malla, S., Wilson, R., Aboobaker, A., Nishimura, O., Hirao, Y., Tarui, H., Agata, K., Garcia-Fernandez, J., Ram, J., Mar-any, G., Mun, A., Kreshchenko, N., Pag’an, O., Deats, S., Baker, D., Montgomery, E., Wilk, G., Tenaglia, M., Semon, J., Ramakrishnan, L., Amatya, C., DeSaer, C., Dalhoff, Z., Eggerichs, M., Magoč, T., Salzberg, S., Grabherr, M., Haas, B., Yassour, M., Zerbino, D., Birney, E., Schulz, M., Zerbino, D., Vingron, M., Birney, E., Langmead, B., Trapnell, C., Pop, M., Salzberg, S., Li, B., Dewey, C., Li, W., Godzik, A., Conesa, A., G’otz, S., Garc’ıa-G’omez, J., Terol, J., Tal’on, M., Robles, M., Lechner, M., Findeiss, S., Steiner, L., Marz, M., Stadler, P., Prohaska, S., Logan-Klumpler, F., Silva, N., Boehme, U., Rogers, M., Velarde, G., McQuillan, J., Carver, T., Aslett, M., Olsen, C., Subramanian, S., Phan, I., Farris, C., Mitra, S., Ramasamy, G., Wang, H., Tivey, A., Jackson, A., Houston, R., Parkhill, J., Holden, M., Harb, O., Brunk, B., Myler, P., Roos, D., Carrington, M., Smith, D., Hertz-Fowler, C., Berriman, M., Krzywinski, M., Schein, J., Birol, I., Connors, J., Gascoyne, R., Horsman, D., Jones, S., Marra, M., Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., Madden, T., Pruitt, K., Brown, G., Hiatt, S., Thibaud-Nissen, F., Astashyn, A., Ermolaeva, O., Farrell, C., Hart, J., Landrum, M., McGarvey, K., Murphy, M., Rask-Andersen, M., Alm’en, M., Schïoth, H., Milligan, J., Jolly, E., Schneider, C., Rasband, W., Eliceiri, K., Noldus, L., Spink, A., Tegelenbosch, R., Koressaar, T., Remm, M., Rouhana, L., Weiss, J., Forsthoefel, D., Lee, H., King, R., Inoue, T., Shibata, N., Agata, K., Newmark, P, Kao, D., Felix, D., Aboobaker, A., Patocka, N., Ribeiro, P, Jones, P., Binns, D., Chang, H.-Y., Fraser, M., Li, W., McAnulla, C., McWilliam, H., Maslen, J., Mitchell, A., Nuka, G., Pesseat, S., Quinn, A., Sangrador-Vegas, A., Scheremetjew, M., Yong, S.-Y., Lopez, R., Hunter, S., Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., Tanabe, M., Hetrick, B., Han, M., Helgeson, L., Nolen, B., Nogi, T., Zhang, D., Chan, J., Marchant, J., Crowther, G., Shanmugam, D., Carmona, S., Doyle, M., Hertz-Fowler, C., Berriman, M., Nwaka, S., Wang, B., Collins, J., Newmark, PA, 2015. Functional analysis of Girardia tigrina transcriptome seeds pipeline for anthelmintic target discovery. Parasit. Vectors 8, 34. https://doi.org/10.1186/s13071-014-0622-3
  31. WHO, 2015. WHO | Breast cancer: prevention and control [WWW Document]. WHO. URL https://www.who.int/cancer/detection/breastcancer/en/
  32. Wolfinger, M.T., Svrcek-Seiler, W.A., Flamm, C., Hofacker, I.L., Stadler, P.F., 2004. Efficient computation of RNA folding dynamics. J. Phys. A. Math. Gen. 37, 4731–4741. https://doi.org/10.1088/0305-4470/37/17/005
  33. Wu, D., Rice, C.M., Wang, X., 2012. Cancer bioinformatics: A new approach to systems clinical medicine. BMC Bioinformatics. https://doi.org/10.1186/1471-2105-13-71
  34. Zaleska, K., 2015. MiRNA - Therapeutic tool in breast cancer? Where are we now? Reports Pract. Oncol. Radiother. https://doi.org/10.1016/j.rpor.2014.10.009

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WJC: Walisongo Journal of Chemistry
Published by the Department of Chemistry
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ISSN: 2549-385X (Print)
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