Intragenic MicroRNAs Binding Sites in MRNAs of Genes Involved in Carcinogenesis

MiRNAs participate in gene regulation of translation. Some studies have investigated the interactions between genes and intragenic miRNAs. It is important to study the miRNA binding sites of genes involved in carcinogenesis. RNAHybrid 2.1 and ERNAhybrid programmes were used to compute the hybridization free energy of miRNA binding sites. Of these 54 mRNAs, 22.6%, 37.7%, and 39.7% of miRNA binding sites were present in the 5'UTRs, CDSs, and 3'UTRs, respectively. The density of the binding sites for miRNAs in the 5'UTR ranged from 1.6 to 43.2 times and from 1.8 to 8.0 times greater than in the CDS and 3'UTR, respectively. Three types of miRNA interactions with mRNAs have been revealed: 5'- dominant canonical, 3'-compensatory, and complementary binding sites. MiRNAs regulate gene expression, and information on the interactions between miRNAs and mRNAs could be useful in molecular medicine. We recommend that newly described sites undergo validation by experimental investigation.
{"references":["V. Ambros, \"microRNAs: tiny regulators with great potential\", Cell, vol.\n7, no. 107, pp. 823-6. 2001.","V. N. Kim, J. Han, M.C. Siomi, \"Biogenesis of small RNAs in animals\",\nNat Rev Mol Cell Biol, no. 10, pp. 126-139. 2009.","Y. K. Kim, V. N. Kim \"Processing of intronic microRNAs\", Embo J, no.\n26, pp. 775-783. 2007.","A. Rodriguez, S. Griffiths-Jones, J. L. Ashurst, A. Bradley, \"Identification\nof mammalian microRNA host genes and transcription units\" Genome\nRes, no. 14, pp. 1902-1910. 2004.","V. Maselli, D. Di Bernardo, S. Banfi, \"CoGemiR: A comparative\ngenomics microRNA database\", BMC Genomics, no. 9, pp. 457. 2008.","B. N. Davis, A. Hata, \"Regulation of MicroRNA Biogenesis: A miRiad of\nmechanisms\", Cell Commun. Signal, no. 10, pp. 7:18. 2009.","M. Selbach, B. Schwanhausser, N. Thierfelder, Z. Fang, R. Khanin, N.\nRajewsky, \"Widespread changes in protein synthesis induced by\nmicroRNAs\", Nature, no. 455, pp. 58-63. 2008.","B. Zhang, X. Pan, G. P. Cobb, T.A. Anderson, \"microRNAs as oncogenes\nand tumor suppressors\", Dev Biol, no. 302, pp. 1-12. 2007.","L. Zhang, J. Huang, N. Yang, \"microRNAs exhibit high frequency\ngenomic alterations in human cancer\", Proc Natl Acad Sci USA, no. 103,\npp. 9136-41. 2006.\n[10] X. Zhou, C. Marian, K. H. Makambi, O. Kosti, B. V. Kallakury, C. A.\nLoffredo, Y. L. Zheng, \"MicroRNA-9 as Potential Biomarker for Breast\nCancer Local Recurrence and Tumor Estrogen Receptor Status\", PLoS\nOne,; vol. 6, no. 7, pp. E39011. 2012.\n[11] C. Wang, X. Zheng, C. Shen, Y. Shi, \"MicroRNA-203 suppresses cell\nproliferation and migration by targeting BIRC5 and LASP1 in human\ntriple-negative breast cancer cells\", J Exp Clin Cancer Res, vol. 1, no.\n31, pp. 58. 2012.\n[12] M. Raychaudhuri, T. Schuster, T. Buchner, K. Malinowsky, H. Bronger,\nU. Schwarz-Boeger, H. Höfler, S. Avril, \"Intratumoral Heterogeneity of\nMicroRNA Expression in Breast Cancer\", J Mol Diagn, vol. 4, no. 14,\npp. 376-84. 2012.\n[13] R. Liu, J. Liao , M. Yang , J. Sheng , H. Yang, Y. Wang, E. Pan, W.\nGuo, Y. Pu, S. J. Kim, L. Yin, \"The cluster of miR-143 and miR-145\naffects the risk for esophageal squamous cell carcinoma through coregulating\nfascin homolog 1\", PLoS One, vol. 3, no. 7, pp. e33987. 2012.\n[14] S. C. Li, Y. L. Liao, M. R. Ho, K. W. Tsai, C. H. Lai, W. C. Lin,\n\"miRNA arm selection and isomiR distribution in gastric cancer\", BMC\nGenomics, vol 13, pp. S13. 2012.\n[15] J. Zhang, Z. Xiao, D. Lai, J. Sun, C. He, Z. Chu, H. Ye, S. Chen, J.\nWang, \"miR-21, miR-17 and miR-19a induced by phosphatase of\nregenerating liver-3 promote the proliferation and metastasis of colon\ncancer\", Br J Cancer, vol. 2, no. 107, pp. 352-9. 2012.\n[16] A. J. Schetter, H. Okayama, C. C. Harris, \"The Role of MicroRNAs in\nColorectal Cancer\", Cancer J, vol. 3, no. 18, pp. 244-52. 2012.\n[17] L. H. Yang, Z. Dong, Z. H. Gong, \"Extracellular miRNA: a novel\nmolecular biomarker for lung cancer\", Yi Chuan, vol. 6, no. 34, pp. 651-\n8. 2012.\n[18] R. Kumarswamy, I. Volkmann, T. Thum, \"Regulation and function of\nmiRNA-21 in health and disease\", RNA Biology, vol. 5, no. 8, pp. 706-\n13. 2011.\n[19] E. Meiri, W. C. Mueller, S. Rosenwald, M. Zepeniuk, E. Klinke, T.B.\nEdmonston, \"A Second-Generation MicroRNA-Based Assay for\nDiagnosing Tumor Tissue Origin\", Oncologist, vol. 6, no. 17, pp. 801-\n12. 2012.\n[20] M. G. Schrauder, R. Strick, R. Schulz-Wendtland, P. L. Strissel, L.\nKahmann, C. R. Loehberg, \"Circulating micro-RNAs as potential bloodbased\nmarkers for early stage breast cancer detection\", PLoS One, vol. 1,\nno. 7, pp. e29770. 2012.\n[21] S. Barik, \"An intronic microRNA silences genes that are functionally\nantagonistic to its host gene\", Nucleic Acids Res, no. 36, pp. 5232-5241.\n2008.\n[22] C. Delay, F. Calon, P. Matthews, S. Hébert, \"Alzheimer-specific\nvariants in the 3'UTR of amyloid precursor protein affect microRNA\nfunction\", Molecular neurodegeneration, no. 6, pp. 70. 2011.\n[23] M. V. Iorio, C. M. Croce, \"MicroRNAs in cancer: small molecules with\na huge impact\", J. Clin. Oncol., no. 27, pp. 5848-5856. 2009.\n[24] M. Isik, H. Korswagen, E. Berezikov, \"Expression patterns of intronic\nmicroRNAs in Caenorhabditis elegans\", Silence, no. 1, pp. 1758-907X.\n2010.\n[25] J. Kruger, M. Rehmsmeier, \"RNAhybrid: microRNA target prediction\neasy, fast and flexible\", Nucleic Acids Res, no. 34, pp. W451-454.\n2006.\n[26] J. Satoh, H. Tabunoki, \"Comprehensive analysis of human microRNA\ntarget networks\", BioData Mining, no. 4, pp. 17. 2011.\n[27] A. Duursma, M. Kedde, M. Schrier, C. Sage, R. Agami, \"miR-148\ntargets human DNMT3b protein coding region\", RNA, no. 14, pp. 872-\n877. 2008.\n[28] I. Elcheva, F. Goswami, K. Noubissi, V. Spiegelman, \"CRD-BP protects\nthe coding region of βTrCP1 mRNA from miR-183-mediated\ndegradation\", Mol. Cell, no. 35, pp. 240-246. 2009.\n[29] S. Kulkarni, R. Savan, Y. Qi, \"Differential microRNA regulation of\nHLA-C expression and its association with HIV control\", Nature, no.\n472, pp. 495-499. 2011.\n[30] F. Moretti, R. Thermann, M. Hentze, \"Mechanism of translational\nregulation by miR-2 from sites in the 5' untranslated region or the open\nreading frame\", RNA, no. 16, pp. 2493-2502. 2010.\n[31] N. P. Tsai, Y. L. Lin, L. N. Wei, \"MicroRNA mir-346 targets the 5'UTR\nof RIP140 mRNA and up-regulates its protein expression\", Biochem. J.,\nno. 424, pp. 411-418. 2009.\n[32] I. Lee, S. S. Ajay, J. I. Yook, H. S. Kim, S. H. Hong, N. H. Kim, S. M.\nDhanasekaran, A. M. Chinnaiyan, B. D. Athey, \"New class of\nmicroRNA targets containing simultaneous 5ÔÇ▓-UTR and 3 ÔÇ▓-UTR\ninteraction sites\", Genome Res, vol. 7, no. 19, pp. 1175-1183. 2009.\n[33] A. Issabekova, O. Berillo, M. Regnier, A. T. Ivashchenko, \"Interactions\nof intergenic microRNAs with mRNAs of genes involved in\ncarcinogenesis\", Biomedical Informatics, vol. 11, no. 8, pp. 513-518.\n2012.\n[34] D. Betel, A. Koppal, P. Agius, C. Sander, C. L. Betel, \"Comprehensive\nmodeling of microRNA targets predicts functional non-conserved and\nnon-canonical sites\", Genome Biology, no. 11, pp. R90. 2010.\n[35] S. Ji, G. Ye, J. Zhang, L. Wang, T. Wang, Z. Wang, T. Zhang, G.\nWang, Z. Guo, Y. Luo, J. Cai, J.Y. Yang, \"miR-574-5p negatively\nregulates Qki6/7 to impact β-catenin/Wnt signalling and the\ndevelopment of colorectal cancer\", Gut. 10.1136/gutjnl-2011-301083.\n2012\n[36] K. M. Foss, C. Sima, D. Ugolini, M. Neri, K. E. Allen, G. J. Weiss,\n\"miR-1254 and miR-574-5p: serum-based microRNA biomarkers for\nearly-stage non-small cell lung cancer\", J Thorac Oncol, vol. 3, no. 6,\npp. 482-8. 2011.\n[37] W. Wang, L. J. Zhao, Y. X. Tan, H. Ren, Z. T. Qi, \"MiR-138 induces\ncell cycle arrest by targeting cyclin D3\", Carcinogenesis, vol. 5, no. 33,\npp. 1113-20. 2012.\n[38] T. H. Kim, Y. K. Kim, Y. Kwon, J. H. Heo, H. Kang, G. Kim, H. J. An,\n\"Deregulation of miR-519a, 153, and 485-5p and its clinicopathological\nrelevance in ovarian epithelial tumours\", Histopathology, vol. 5, no. 57,\npp. 734-43. 2010.\n[39] A. Torres, K. Torres, A. Pesci, M. Ceccaroni, T. Paszkowski, P.\nCassandrini, G. Zamboni, R. Maciejewski, \"Deregulation of miR-100,\nmiR-99a and miR-199b in tissues and plasma coexists with increased\nexpression of mTOR kinase in endometrioid endometrial carcinoma\",\nBMC Cancer, vol. 1, no. 12, pp. 369. 2012."]}