MiRNAs as Regulators of Tumour Suppressor Expression
Tumour suppressors are key participants in the
prevention of cancer. Regulation of their expression through
miRNAs is important for comprehensive translation inhibition of
tumour suppressors and elucidation of carcinogenesis mechanisms.
We studies the possibility of 1521 miRNAs to bind with 873 mRNAs
of human tumour suppressors using RNAHybrid 2.1 and ERNAhybrid
programmes. Only 978 miRNAs were found to be
translational regulators of 812 mRNAs, and 61 mRNAs did not have
any miRNA binding sites. Additionally, 45.9% of all miRNA binding
sites were located in coding sequences (CDSs), 33.8% were located
in 3' untranslated region (UTR), and 20.3% were located in the
5'UTR. MiRNAs binding with more than 50 target mRNAs and
mRNAs binding with several miRNAs were selected. Hsa-miR-5096
had 15 perfectly complementary binding sites with mRNAs of 14
tumour suppressors. These newly indentified miRNA binding sites
can be used in the development of medicines (anti-sense therapies)
for cancer treatment.
[1] A. Chow, C.L. Arteaga, S.E. Wang, "When tumor suppressor TGFβ
meets the HER2 (ERBB2) oncogene", J Mammary Gland Biol
Neoplasia, vol. 2, no. 16, pp. 81-8. 2011.
[2] A. Andersen, D.A. Jones, "APC and DNA Demethylation in Cell Fate
Specification and Intestinal Cancer", Adv Exp Med Biol, no. 754, pp.
167-77. 2013.
[3] M.A. Cortez, C. Bueso-Ramos, J. Ferdin, G. Lopez-Berestein, A.K.
Sood, G.A. Calin, "MicroRNAs in body fluids-the mix of hormones and
biomarkers", Nat Rev Clin Oncol, vol. 8, no. 8, pp. 467-77. 2011.
[4] M. Ul Hussain, "Micro-RNAs (miRNAs): genomic organisation,
biogenesis and mode of action", Cell Tissue Res, vol. 2, no. 349, pp.
405-13. 2012.
[5] Y.K. Kim, V.N. Kim, "Processing of intronic microRNAs", Embo J, no.
26, pp. 775-783. 2007.
[6] 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.
[7] A. Allegra, A. Alonci, S. Campo, G. Penna, A. Petrungaro, D. Gerace, C.
Musolino, "Circulating microRNAs: New biomarkers in diagnosis,
prognosis and treatment of cancer", Int J Oncol, 1647. 2012. doi:
10.3892/ijo.2012.1647.
[8] Y. Zhang, S. Takahashi, A. Tasaka, T. Yoshima, H. Ochi, K. Chayama,
"Involvement of microRNA-224 in cell proliferation, migration,
invasion and anti-apoptosis in hepatocellular carcinoma", J
Gastroenterol Hepatol, pp. 1440-1746. 2012. doi: 10.1111/j.1440-
1746.2012.07271.x.
[9] H. Cheng1, L. Zhang, D.E. Cogdell, H. Zheng, A.J. Schetter, M. Nykter,
C. Curtis. Harris, K. Chen, S.R. Hamilton, W. Zhang, "Circulating
Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon", Cancer
and Predicts Poor Prognosis, vol. 6, no. 3, pp. E17745. 2011.
[10] 10 D. Long, C.Y. Chan, Y. Ding, "Analysis of microRNA-target
interactions by a target structure based hybridization model", Pac Symp
Biocomput, pp. 64-74. 2008.
[11] D. Goldoni, J.M. Yarham, M.K. McGahon, A. O'Connor, J. Guduric-
Fuchs, K. Edgar, D.M. McDonald, D.A. Simpson, A. Collins, "A novel
dual-fluorescence strategy for functionally validating microRNA targets
in 3-prime untranslated regions: regulation of the inward rectifier
potassium channel Kir2.1 by miR-212", Biochem J. 2012.
[12] B.L. Brewster, F. Rossiello, J.D. French, S.L. Edwards, M. Wong, A.
Wronski, P. Whiley, N. Waddell, X. Chen, B. Bove, Kconfab, J.L.
Hopper, E.M. John, I. Andrulis, "Identification of fifteen novel germline
variants in the BRCA1 3'UTR reveals a variant in a breast cancer case
that introduces a functional miR-103 target site", Hum Mutat. 2012. doi:
10.1002/humu.22159.
[13] J. Satoh, H. Tabunoki, "Comprehensive analysis of human microRNA
target networks", BioData Mining, no. 4, pp. 17. 2011.
[14] X. Zhou, X. Duan, J. Qian, F. Li, "Abundant conserved microRNA
target sites in the 5'-untranslated region and coding sequence", Genetica,
vol. 2, no. 137, pp. 159-64. 2009.
[15] A. Issabekova, O. Berillo, M. Regnier, A. Ivashchenko, "Interactions of
intergenic microRNAs with mRNAs of genes involved in
carcinogenesis", Biomedical Informatics, vol. 11, no. 8, pp. 513-518.
2012.
[16] 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.
[17] 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.
[18] G. Tzimagiorgis, E.Z. Michailidou, A. Kritis, A.K. Markopoulos, S.
Kouidou, "Recovering circulating extracellular or cell-free RNA from
bodily fluids", Cancer Epidemiol, vol. 6, no. 35, pp. 580-9. 2011.
[19] J.A. Weber, D.H. Baxter, S. Zhang, D.Y. Huang, K.H. Huang, M.J. Lee,
D.J. Galas, K. Wang, "The microRNA spectrum in 12 body fluids", Clin
Chem, vol. 11, no. 56, pp. 1733-41. 2010.
[20] R. Albulescu, M. Neagu, L. Albulescu, C. Tanase, "Tissular and soluble
miRNAs for diagnostic and therapy improvement in digestive tract
cancers", Expert Rev Mol Diagn, vol. 1, no. 11, pp. 101-20. 2011.
[21] M.V. Iorio, C.M. Croce, "MicroRNA dysregulation in cancer:
diagnostics, monitoring and therapeutics. A comprehensive review",
EMBO Mol Med, vol. 3, no. 4, pp. 143-59. 2012.
[22] A. T. Ivashchenko, A. S. Issabekova, O. A. Berillo "Peculiarities of
miR-1279 binding sites in CDS of ðáðóðáN12, MSH6 and ZEB1
oncogenes of human and animal". unpublished.
[1] A. Chow, C.L. Arteaga, S.E. Wang, "When tumor suppressor TGFβ
meets the HER2 (ERBB2) oncogene", J Mammary Gland Biol
Neoplasia, vol. 2, no. 16, pp. 81-8. 2011.
[2] A. Andersen, D.A. Jones, "APC and DNA Demethylation in Cell Fate
Specification and Intestinal Cancer", Adv Exp Med Biol, no. 754, pp.
167-77. 2013.
[3] M.A. Cortez, C. Bueso-Ramos, J. Ferdin, G. Lopez-Berestein, A.K.
Sood, G.A. Calin, "MicroRNAs in body fluids-the mix of hormones and
biomarkers", Nat Rev Clin Oncol, vol. 8, no. 8, pp. 467-77. 2011.
[4] M. Ul Hussain, "Micro-RNAs (miRNAs): genomic organisation,
biogenesis and mode of action", Cell Tissue Res, vol. 2, no. 349, pp.
405-13. 2012.
[5] Y.K. Kim, V.N. Kim, "Processing of intronic microRNAs", Embo J, no.
26, pp. 775-783. 2007.
[6] 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.
[7] A. Allegra, A. Alonci, S. Campo, G. Penna, A. Petrungaro, D. Gerace, C.
Musolino, "Circulating microRNAs: New biomarkers in diagnosis,
prognosis and treatment of cancer", Int J Oncol, 1647. 2012. doi:
10.3892/ijo.2012.1647.
[8] Y. Zhang, S. Takahashi, A. Tasaka, T. Yoshima, H. Ochi, K. Chayama,
"Involvement of microRNA-224 in cell proliferation, migration,
invasion and anti-apoptosis in hepatocellular carcinoma", J
Gastroenterol Hepatol, pp. 1440-1746. 2012. doi: 10.1111/j.1440-
1746.2012.07271.x.
[9] H. Cheng1, L. Zhang, D.E. Cogdell, H. Zheng, A.J. Schetter, M. Nykter,
C. Curtis. Harris, K. Chen, S.R. Hamilton, W. Zhang, "Circulating
Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon", Cancer
and Predicts Poor Prognosis, vol. 6, no. 3, pp. E17745. 2011.
[10] 10 D. Long, C.Y. Chan, Y. Ding, "Analysis of microRNA-target
interactions by a target structure based hybridization model", Pac Symp
Biocomput, pp. 64-74. 2008.
[11] D. Goldoni, J.M. Yarham, M.K. McGahon, A. O'Connor, J. Guduric-
Fuchs, K. Edgar, D.M. McDonald, D.A. Simpson, A. Collins, "A novel
dual-fluorescence strategy for functionally validating microRNA targets
in 3-prime untranslated regions: regulation of the inward rectifier
potassium channel Kir2.1 by miR-212", Biochem J. 2012.
[12] B.L. Brewster, F. Rossiello, J.D. French, S.L. Edwards, M. Wong, A.
Wronski, P. Whiley, N. Waddell, X. Chen, B. Bove, Kconfab, J.L.
Hopper, E.M. John, I. Andrulis, "Identification of fifteen novel germline
variants in the BRCA1 3'UTR reveals a variant in a breast cancer case
that introduces a functional miR-103 target site", Hum Mutat. 2012. doi:
10.1002/humu.22159.
[13] J. Satoh, H. Tabunoki, "Comprehensive analysis of human microRNA
target networks", BioData Mining, no. 4, pp. 17. 2011.
[14] X. Zhou, X. Duan, J. Qian, F. Li, "Abundant conserved microRNA
target sites in the 5'-untranslated region and coding sequence", Genetica,
vol. 2, no. 137, pp. 159-64. 2009.
[15] A. Issabekova, O. Berillo, M. Regnier, A. Ivashchenko, "Interactions of
intergenic microRNAs with mRNAs of genes involved in
carcinogenesis", Biomedical Informatics, vol. 11, no. 8, pp. 513-518.
2012.
[16] 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.
[17] 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.
[18] G. Tzimagiorgis, E.Z. Michailidou, A. Kritis, A.K. Markopoulos, S.
Kouidou, "Recovering circulating extracellular or cell-free RNA from
bodily fluids", Cancer Epidemiol, vol. 6, no. 35, pp. 580-9. 2011.
[19] J.A. Weber, D.H. Baxter, S. Zhang, D.Y. Huang, K.H. Huang, M.J. Lee,
D.J. Galas, K. Wang, "The microRNA spectrum in 12 body fluids", Clin
Chem, vol. 11, no. 56, pp. 1733-41. 2010.
[20] R. Albulescu, M. Neagu, L. Albulescu, C. Tanase, "Tissular and soluble
miRNAs for diagnostic and therapy improvement in digestive tract
cancers", Expert Rev Mol Diagn, vol. 1, no. 11, pp. 101-20. 2011.
[21] M.V. Iorio, C.M. Croce, "MicroRNA dysregulation in cancer:
diagnostics, monitoring and therapeutics. A comprehensive review",
EMBO Mol Med, vol. 3, no. 4, pp. 143-59. 2012.
[22] A. T. Ivashchenko, A. S. Issabekova, O. A. Berillo "Peculiarities of
miR-1279 binding sites in CDS of ðáðóðáN12, MSH6 and ZEB1
oncogenes of human and animal". unpublished.
@article{"International Journal of Medical, Medicine and Health Sciences:53478", author = "Olga A. Berillo and Gaukhar K. Baidildinova and Аnatoliy Т. Ivashchenko", title = "MiRNAs as Regulators of Tumour Suppressor Expression", abstract = "Tumour suppressors are key participants in the
prevention of cancer. Regulation of their expression through
miRNAs is important for comprehensive translation inhibition of
tumour suppressors and elucidation of carcinogenesis mechanisms.
We studies the possibility of 1521 miRNAs to bind with 873 mRNAs
of human tumour suppressors using RNAHybrid 2.1 and ERNAhybrid
programmes. Only 978 miRNAs were found to be
translational regulators of 812 mRNAs, and 61 mRNAs did not have
any miRNA binding sites. Additionally, 45.9% of all miRNA binding
sites were located in coding sequences (CDSs), 33.8% were located
in 3' untranslated region (UTR), and 20.3% were located in the
5'UTR. MiRNAs binding with more than 50 target mRNAs and
mRNAs binding with several miRNAs were selected. Hsa-miR-5096
had 15 perfectly complementary binding sites with mRNAs of 14
tumour suppressors. These newly indentified miRNA binding sites
can be used in the development of medicines (anti-sense therapies)
for cancer treatment.", keywords = "Exonic miRNA, intergenic miRNA, intronic
miRNA, tumor suppressor.", volume = "7", number = "1", pages = "30-5", }