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.
[1] V. Ambros, "microRNAs: tiny regulators with great potential", Cell, vol.
7, no. 107, pp. 823-6. 2001.
[2] V. N. Kim, J. Han, M.C. Siomi, "Biogenesis of small RNAs in animals",
Nat Rev Mol Cell Biol, no. 10, pp. 126-139. 2009.
[3] Y. K. Kim, V. N. Kim "Processing of intronic microRNAs", Embo J, no.
26, pp. 775-783. 2007.
[4] A. Rodriguez, S. Griffiths-Jones, J. L. Ashurst, A. Bradley, "Identification
of mammalian microRNA host genes and transcription units" Genome
Res, no. 14, pp. 1902-1910. 2004.
[5] V. Maselli, D. Di Bernardo, S. Banfi, "CoGemiR: A comparative
genomics microRNA database", BMC Genomics, no. 9, pp. 457. 2008.
[6] B. N. Davis, A. Hata, "Regulation of MicroRNA Biogenesis: A miRiad of
mechanisms", Cell Commun. Signal, no. 10, pp. 7:18. 2009.
[7] M. Selbach, B. Schwanhausser, N. Thierfelder, Z. Fang, R. Khanin, N.
Rajewsky, "Widespread changes in protein synthesis induced by
microRNAs", Nature, no. 455, pp. 58-63. 2008.
[8] B. Zhang, X. Pan, G. P. Cobb, T.A. Anderson, "microRNAs as oncogenes
and tumor suppressors", Dev Biol, no. 302, pp. 1-12. 2007.
[9] L. Zhang, J. Huang, N. Yang, "microRNAs exhibit high frequency
genomic alterations in human cancer", Proc Natl Acad Sci USA, no. 103,
pp. 9136-41. 2006.
[10] X. Zhou, C. Marian, K. H. Makambi, O. Kosti, B. V. Kallakury, C. A.
Loffredo, Y. L. Zheng, "MicroRNA-9 as Potential Biomarker for Breast
Cancer Local Recurrence and Tumor Estrogen Receptor Status", PLoS
One,; vol. 6, no. 7, pp. E39011. 2012.
[11] C. Wang, X. Zheng, C. Shen, Y. Shi, "MicroRNA-203 suppresses cell
proliferation and migration by targeting BIRC5 and LASP1 in human
triple-negative breast cancer cells", J Exp Clin Cancer Res, vol. 1, no.
31, pp. 58. 2012.
[12] M. Raychaudhuri, T. Schuster, T. Buchner, K. Malinowsky, H. Bronger,
U. Schwarz-Boeger, H. Höfler, S. Avril, "Intratumoral Heterogeneity of
MicroRNA Expression in Breast Cancer", J Mol Diagn, vol. 4, no. 14,
pp. 376-84. 2012.
[13] R. Liu, J. Liao , M. Yang , J. Sheng , H. Yang, Y. Wang, E. Pan, W.
Guo, Y. Pu, S. J. Kim, L. Yin, "The cluster of miR-143 and miR-145
affects the risk for esophageal squamous cell carcinoma through coregulating
fascin homolog 1", PLoS One, vol. 3, no. 7, pp. e33987. 2012.
[14] S. C. Li, Y. L. Liao, M. R. Ho, K. W. Tsai, C. H. Lai, W. C. Lin,
"miRNA arm selection and isomiR distribution in gastric cancer", BMC
Genomics, vol 13, pp. S13. 2012.
[15] J. Zhang, Z. Xiao, D. Lai, J. Sun, C. He, Z. Chu, H. Ye, S. Chen, J.
Wang, "miR-21, miR-17 and miR-19a induced by phosphatase of
regenerating liver-3 promote the proliferation and metastasis of colon
cancer", Br J Cancer, vol. 2, no. 107, pp. 352-9. 2012.
[16] A. J. Schetter, H. Okayama, C. C. Harris, "The Role of MicroRNAs in
Colorectal Cancer", Cancer J, vol. 3, no. 18, pp. 244-52. 2012.
[17] L. H. Yang, Z. Dong, Z. H. Gong, "Extracellular miRNA: a novel
molecular biomarker for lung cancer", Yi Chuan, vol. 6, no. 34, pp. 651-
8. 2012.
[18] R. Kumarswamy, I. Volkmann, T. Thum, "Regulation and function of
miRNA-21 in health and disease", RNA Biology, vol. 5, no. 8, pp. 706-
13. 2011.
[19] E. Meiri, W. C. Mueller, S. Rosenwald, M. Zepeniuk, E. Klinke, T.B.
Edmonston, "A Second-Generation MicroRNA-Based Assay for
Diagnosing Tumor Tissue Origin", Oncologist, vol. 6, no. 17, pp. 801-
12. 2012.
[20] M. G. Schrauder, R. Strick, R. Schulz-Wendtland, P. L. Strissel, L.
Kahmann, C. R. Loehberg, "Circulating micro-RNAs as potential bloodbased
markers for early stage breast cancer detection", PLoS One, vol. 1,
no. 7, pp. e29770. 2012.
[21] S. Barik, "An intronic microRNA silences genes that are functionally
antagonistic to its host gene", Nucleic Acids Res, no. 36, pp. 5232-5241.
2008.
[22] C. Delay, F. Calon, P. Matthews, S. Hébert, "Alzheimer-specific
variants in the 3'UTR of amyloid precursor protein affect microRNA
function", Molecular neurodegeneration, no. 6, pp. 70. 2011.
[23] M. V. Iorio, C. M. Croce, "MicroRNAs in cancer: small molecules with
a huge impact", J. Clin. Oncol., no. 27, pp. 5848-5856. 2009.
[24] M. Isik, H. Korswagen, E. Berezikov, "Expression patterns of intronic
microRNAs in Caenorhabditis elegans", Silence, no. 1, pp. 1758-907X.
2010.
[25] J. Kruger, M. Rehmsmeier, "RNAhybrid: microRNA target prediction
easy, fast and flexible", Nucleic Acids Res, no. 34, pp. W451-454.
2006.
[26] J. Satoh, H. Tabunoki, "Comprehensive analysis of human microRNA
target networks", BioData Mining, no. 4, pp. 17. 2011.
[27] A. Duursma, M. Kedde, M. Schrier, C. Sage, R. Agami, "miR-148
targets human DNMT3b protein coding region", RNA, no. 14, pp. 872-
877. 2008.
[28] I. Elcheva, F. Goswami, K. Noubissi, V. Spiegelman, "CRD-BP protects
the coding region of βTrCP1 mRNA from miR-183-mediated
degradation", Mol. Cell, no. 35, pp. 240-246. 2009.
[29] S. Kulkarni, R. Savan, Y. Qi, "Differential microRNA regulation of
HLA-C expression and its association with HIV control", Nature, no.
472, pp. 495-499. 2011.
[30] F. Moretti, R. Thermann, M. Hentze, "Mechanism of translational
regulation by miR-2 from sites in the 5' untranslated region or the open
reading frame", RNA, no. 16, pp. 2493-2502. 2010.
[31] N. P. Tsai, Y. L. Lin, L. N. Wei, "MicroRNA mir-346 targets the 5'UTR
of RIP140 mRNA and up-regulates its protein expression", Biochem. J.,
no. 424, pp. 411-418. 2009.
[32] I. Lee, S. S. Ajay, J. I. Yook, H. S. Kim, S. H. Hong, N. H. Kim, S. M.
Dhanasekaran, A. M. Chinnaiyan, B. D. Athey, "New class of
microRNA targets containing simultaneous 5ÔÇ▓-UTR and 3 ÔÇ▓-UTR
interaction sites", Genome Res, vol. 7, no. 19, pp. 1175-1183. 2009.
[33] A. Issabekova, O. Berillo, M. Regnier, A. T. Ivashchenko, "Interactions
of intergenic microRNAs with mRNAs of genes involved in
carcinogenesis", Biomedical Informatics, vol. 11, no. 8, pp. 513-518.
2012.
[34] D. Betel, A. Koppal, P. Agius, C. Sander, C. L. Betel, "Comprehensive
modeling of microRNA targets predicts functional non-conserved and
non-canonical sites", Genome Biology, no. 11, pp. R90. 2010.
[35] S. Ji, G. Ye, J. Zhang, L. Wang, T. Wang, Z. Wang, T. Zhang, G.
Wang, Z. Guo, Y. Luo, J. Cai, J.Y. Yang, "miR-574-5p negatively
regulates Qki6/7 to impact β-catenin/Wnt signalling and the
development of colorectal cancer", Gut. 10.1136/gutjnl-2011-301083.
2012
[36] K. M. Foss, C. Sima, D. Ugolini, M. Neri, K. E. Allen, G. J. Weiss,
"miR-1254 and miR-574-5p: serum-based microRNA biomarkers for
early-stage non-small cell lung cancer", J Thorac Oncol, vol. 3, no. 6,
pp. 482-8. 2011.
[37] W. Wang, L. J. Zhao, Y. X. Tan, H. Ren, Z. T. Qi, "MiR-138 induces
cell cycle arrest by targeting cyclin D3", Carcinogenesis, vol. 5, no. 33,
pp. 1113-20. 2012.
[38] T. H. Kim, Y. K. Kim, Y. Kwon, J. H. Heo, H. Kang, G. Kim, H. J. An,
"Deregulation of miR-519a, 153, and 485-5p and its clinicopathological
relevance in ovarian epithelial tumours", Histopathology, vol. 5, no. 57,
pp. 734-43. 2010.
[39] A. Torres, K. Torres, A. Pesci, M. Ceccaroni, T. Paszkowski, P.
Cassandrini, G. Zamboni, R. Maciejewski, "Deregulation of miR-100,
miR-99a and miR-199b in tissues and plasma coexists with increased
expression of mTOR kinase in endometrioid endometrial carcinoma",
BMC Cancer, vol. 1, no. 12, pp. 369. 2012.
[1] V. Ambros, "microRNAs: tiny regulators with great potential", Cell, vol.
7, no. 107, pp. 823-6. 2001.
[2] V. N. Kim, J. Han, M.C. Siomi, "Biogenesis of small RNAs in animals",
Nat Rev Mol Cell Biol, no. 10, pp. 126-139. 2009.
[3] Y. K. Kim, V. N. Kim "Processing of intronic microRNAs", Embo J, no.
26, pp. 775-783. 2007.
[4] A. Rodriguez, S. Griffiths-Jones, J. L. Ashurst, A. Bradley, "Identification
of mammalian microRNA host genes and transcription units" Genome
Res, no. 14, pp. 1902-1910. 2004.
[5] V. Maselli, D. Di Bernardo, S. Banfi, "CoGemiR: A comparative
genomics microRNA database", BMC Genomics, no. 9, pp. 457. 2008.
[6] B. N. Davis, A. Hata, "Regulation of MicroRNA Biogenesis: A miRiad of
mechanisms", Cell Commun. Signal, no. 10, pp. 7:18. 2009.
[7] M. Selbach, B. Schwanhausser, N. Thierfelder, Z. Fang, R. Khanin, N.
Rajewsky, "Widespread changes in protein synthesis induced by
microRNAs", Nature, no. 455, pp. 58-63. 2008.
[8] B. Zhang, X. Pan, G. P. Cobb, T.A. Anderson, "microRNAs as oncogenes
and tumor suppressors", Dev Biol, no. 302, pp. 1-12. 2007.
[9] L. Zhang, J. Huang, N. Yang, "microRNAs exhibit high frequency
genomic alterations in human cancer", Proc Natl Acad Sci USA, no. 103,
pp. 9136-41. 2006.
[10] X. Zhou, C. Marian, K. H. Makambi, O. Kosti, B. V. Kallakury, C. A.
Loffredo, Y. L. Zheng, "MicroRNA-9 as Potential Biomarker for Breast
Cancer Local Recurrence and Tumor Estrogen Receptor Status", PLoS
One,; vol. 6, no. 7, pp. E39011. 2012.
[11] C. Wang, X. Zheng, C. Shen, Y. Shi, "MicroRNA-203 suppresses cell
proliferation and migration by targeting BIRC5 and LASP1 in human
triple-negative breast cancer cells", J Exp Clin Cancer Res, vol. 1, no.
31, pp. 58. 2012.
[12] M. Raychaudhuri, T. Schuster, T. Buchner, K. Malinowsky, H. Bronger,
U. Schwarz-Boeger, H. Höfler, S. Avril, "Intratumoral Heterogeneity of
MicroRNA Expression in Breast Cancer", J Mol Diagn, vol. 4, no. 14,
pp. 376-84. 2012.
[13] R. Liu, J. Liao , M. Yang , J. Sheng , H. Yang, Y. Wang, E. Pan, W.
Guo, Y. Pu, S. J. Kim, L. Yin, "The cluster of miR-143 and miR-145
affects the risk for esophageal squamous cell carcinoma through coregulating
fascin homolog 1", PLoS One, vol. 3, no. 7, pp. e33987. 2012.
[14] S. C. Li, Y. L. Liao, M. R. Ho, K. W. Tsai, C. H. Lai, W. C. Lin,
"miRNA arm selection and isomiR distribution in gastric cancer", BMC
Genomics, vol 13, pp. S13. 2012.
[15] J. Zhang, Z. Xiao, D. Lai, J. Sun, C. He, Z. Chu, H. Ye, S. Chen, J.
Wang, "miR-21, miR-17 and miR-19a induced by phosphatase of
regenerating liver-3 promote the proliferation and metastasis of colon
cancer", Br J Cancer, vol. 2, no. 107, pp. 352-9. 2012.
[16] A. J. Schetter, H. Okayama, C. C. Harris, "The Role of MicroRNAs in
Colorectal Cancer", Cancer J, vol. 3, no. 18, pp. 244-52. 2012.
[17] L. H. Yang, Z. Dong, Z. H. Gong, "Extracellular miRNA: a novel
molecular biomarker for lung cancer", Yi Chuan, vol. 6, no. 34, pp. 651-
8. 2012.
[18] R. Kumarswamy, I. Volkmann, T. Thum, "Regulation and function of
miRNA-21 in health and disease", RNA Biology, vol. 5, no. 8, pp. 706-
13. 2011.
[19] E. Meiri, W. C. Mueller, S. Rosenwald, M. Zepeniuk, E. Klinke, T.B.
Edmonston, "A Second-Generation MicroRNA-Based Assay for
Diagnosing Tumor Tissue Origin", Oncologist, vol. 6, no. 17, pp. 801-
12. 2012.
[20] M. G. Schrauder, R. Strick, R. Schulz-Wendtland, P. L. Strissel, L.
Kahmann, C. R. Loehberg, "Circulating micro-RNAs as potential bloodbased
markers for early stage breast cancer detection", PLoS One, vol. 1,
no. 7, pp. e29770. 2012.
[21] S. Barik, "An intronic microRNA silences genes that are functionally
antagonistic to its host gene", Nucleic Acids Res, no. 36, pp. 5232-5241.
2008.
[22] C. Delay, F. Calon, P. Matthews, S. Hébert, "Alzheimer-specific
variants in the 3'UTR of amyloid precursor protein affect microRNA
function", Molecular neurodegeneration, no. 6, pp. 70. 2011.
[23] M. V. Iorio, C. M. Croce, "MicroRNAs in cancer: small molecules with
a huge impact", J. Clin. Oncol., no. 27, pp. 5848-5856. 2009.
[24] M. Isik, H. Korswagen, E. Berezikov, "Expression patterns of intronic
microRNAs in Caenorhabditis elegans", Silence, no. 1, pp. 1758-907X.
2010.
[25] J. Kruger, M. Rehmsmeier, "RNAhybrid: microRNA target prediction
easy, fast and flexible", Nucleic Acids Res, no. 34, pp. W451-454.
2006.
[26] J. Satoh, H. Tabunoki, "Comprehensive analysis of human microRNA
target networks", BioData Mining, no. 4, pp. 17. 2011.
[27] A. Duursma, M. Kedde, M. Schrier, C. Sage, R. Agami, "miR-148
targets human DNMT3b protein coding region", RNA, no. 14, pp. 872-
877. 2008.
[28] I. Elcheva, F. Goswami, K. Noubissi, V. Spiegelman, "CRD-BP protects
the coding region of βTrCP1 mRNA from miR-183-mediated
degradation", Mol. Cell, no. 35, pp. 240-246. 2009.
[29] S. Kulkarni, R. Savan, Y. Qi, "Differential microRNA regulation of
HLA-C expression and its association with HIV control", Nature, no.
472, pp. 495-499. 2011.
[30] F. Moretti, R. Thermann, M. Hentze, "Mechanism of translational
regulation by miR-2 from sites in the 5' untranslated region or the open
reading frame", RNA, no. 16, pp. 2493-2502. 2010.
[31] N. P. Tsai, Y. L. Lin, L. N. Wei, "MicroRNA mir-346 targets the 5'UTR
of RIP140 mRNA and up-regulates its protein expression", Biochem. J.,
no. 424, pp. 411-418. 2009.
[32] I. Lee, S. S. Ajay, J. I. Yook, H. S. Kim, S. H. Hong, N. H. Kim, S. M.
Dhanasekaran, A. M. Chinnaiyan, B. D. Athey, "New class of
microRNA targets containing simultaneous 5ÔÇ▓-UTR and 3 ÔÇ▓-UTR
interaction sites", Genome Res, vol. 7, no. 19, pp. 1175-1183. 2009.
[33] A. Issabekova, O. Berillo, M. Regnier, A. T. Ivashchenko, "Interactions
of intergenic microRNAs with mRNAs of genes involved in
carcinogenesis", Biomedical Informatics, vol. 11, no. 8, pp. 513-518.
2012.
[34] D. Betel, A. Koppal, P. Agius, C. Sander, C. L. Betel, "Comprehensive
modeling of microRNA targets predicts functional non-conserved and
non-canonical sites", Genome Biology, no. 11, pp. R90. 2010.
[35] S. Ji, G. Ye, J. Zhang, L. Wang, T. Wang, Z. Wang, T. Zhang, G.
Wang, Z. Guo, Y. Luo, J. Cai, J.Y. Yang, "miR-574-5p negatively
regulates Qki6/7 to impact β-catenin/Wnt signalling and the
development of colorectal cancer", Gut. 10.1136/gutjnl-2011-301083.
2012
[36] K. M. Foss, C. Sima, D. Ugolini, M. Neri, K. E. Allen, G. J. Weiss,
"miR-1254 and miR-574-5p: serum-based microRNA biomarkers for
early-stage non-small cell lung cancer", J Thorac Oncol, vol. 3, no. 6,
pp. 482-8. 2011.
[37] W. Wang, L. J. Zhao, Y. X. Tan, H. Ren, Z. T. Qi, "MiR-138 induces
cell cycle arrest by targeting cyclin D3", Carcinogenesis, vol. 5, no. 33,
pp. 1113-20. 2012.
[38] T. H. Kim, Y. K. Kim, Y. Kwon, J. H. Heo, H. Kang, G. Kim, H. J. An,
"Deregulation of miR-519a, 153, and 485-5p and its clinicopathological
relevance in ovarian epithelial tumours", Histopathology, vol. 5, no. 57,
pp. 734-43. 2010.
[39] A. Torres, K. Torres, A. Pesci, M. Ceccaroni, T. Paszkowski, P.
Cassandrini, G. Zamboni, R. Maciejewski, "Deregulation of miR-100,
miR-99a and miR-199b in tissues and plasma coexists with increased
expression of mTOR kinase in endometrioid endometrial carcinoma",
BMC Cancer, vol. 1, no. 12, pp. 369. 2012.
@article{"International Journal of Biological, Life and Agricultural Sciences:63214", author = "Olga A. Berillo and Assel S. Issabekova and Anatoly T. Ivashchenko", title = "Intragenic MicroRNAs Binding Sites in MRNAs of Genes Involved in Carcinogenesis", abstract = "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.", keywords = "Exon, intron, miRNA, oncogene.", volume = "7", number = "1", pages = "68-6", }
