Характеристики взаимодействия miRNA C 5’UTR, CDS, 3’UTR mRNA кандидатных генов субтипов рака молочной железы
DOI:
https://doi.org/10.26577/eb-2018-2-1326Аннотация
Различные субтипы рака молочной железы отличаются набором кандидатных генов, участвующих в развитии этого заболевания. Экспрессия многих генов регулируется связыванием их mRNA с miRNA, поэтому требуется выявить, какие кандидатные гены онкогенеза и в какой степени могут взаимодействовать с miRNA. Цель настоящей работы заключалась в установлении характеристик взаимодействия известных 3701 miRNA с mRNA 92 кандидатных генов субтипов рака молочной железы. Из 25 кандидатных генов субтипа her2 мишенями miRNA являлись 19 генов. Сайты связывания 67 miRNA располагались в 5’UTR, CDS, 3’UTR и средняя свободная энергия связывания (DG) miRNA с mRNA равнялась -120,2 ± -7,6 kJ/mole, -123,6 ± -9,8 kJ/ mole, -110,4 ± -9,8 kJ/mole, соответственно. Для диагностики субтипа her2 рекомендованы 31 ассоциация miRNA с mRNA, имеющие свободную энергию взаимодействия более -120 kJ/mole. Из 47 кандидатных генов субтипа triple-negative мишенями miRNA являлись 33 гена. Сайты связывания 90 miRNA располагались в 5’UTR, CDS, 3’UTR и средняя величина DG связывания miRNA с mRNA равнялась -123,5 ± -7,0 kJ/mole, -114,1 ± –7,9 kJ/mole, -106,9 ± –4,9 kJ/mole, соответственно. Для диагностики субтипа triple-negative рекомендованы 36 ассоциаций miR- NA с mRNA. Из 20 кандидатных генов субтипов luminal A и B мишенями miRNA являлись 14 генов. Сайты связывания 86 miRNA располагались в 5’UTR, CDS, 3’UTR и средняя величина DG связывания miRNA с mRNA равнялась -121.2 ± -9,5 kJ/mole, 120,4 ± -7,8 kJ/mole, -118,9 ± -8,1 kJ/mole, соответственно. Для диагностики субтипов luminal A и B рекомендованы 51 ассоциация miRNA с mRNA. В mRNA многих генов выявлены участки, содержащие два и более сайтов связывания miRNA с наложением их нуклеотидных последовательностей, что в несколько раз уменьшает долю сайтов связывания в составе нуклеотидов в 5’UTR, CDS и 3’UTR. На основе полученных результатов рекомендуются группы ассоциаций miRNA и mRNA кандидатных генов для разработки методов диагностики субтипов рака молочной железы.
Ключевые слова: miRNA, mRNA, субтипы рака молочной железы, гены-мишени.
Библиографические ссылки
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Peurala H., Greco D., Heikkinen T., Kaur S., Bartkova �., �amshidi M., Aittomäki K., Heikkilä P., Bartek �., Blomqvist C., Bützow R., Nevanlinna H. MiR-34a expression has an effect for lower risk of metastasis and associates with expression patterns predicting clinical outcome in breast cancer �� P�oS �ne. – 2011. – Vol. 6, No. 11. – P. e26122. doi:10.1371�journal.pone.0026122. Ray A., Ray B.K. Induction of Ras by SAF-1�MAZ through a feed-forward loop promotes angiogenesis in breast cancer �� Can-
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Wang C., Zheng X., Shen C., Shi �. MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and �ASP1 in human triple-negative breast cancer cells �� � Exp Clin Cancer Res. – 2012. – Vol. 31. – P. 58. doi: 10.1186�1756-9966-31-58.
References
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Banin Hirata B.K., �da �.M., �osi Guembarovski R., Ariza C.B., de �liveira C.E., Watanabe M.A. (2014) Molecular markers for breast cancer: prediction on tumor behavior. Dis Markers, vol. 2014, pp. 513158. doi: 10.1155�2014�513158.
Barba M., Vici P., Pizzuti �., Di �auro �., Sergi D., Di Benedetto A., Ercolani C., Sperati F., Terrenato I., Botti C., Mentuccia
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Biomed Research International, vol. 2014, pp. e11.
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Kool E.T. (2001) Hydrogen bonding, base stacking, and steric effects in DNA replication. Annual Review of Biophysics and Biomolecular Structure, vol.30, pp. 1–22.
�eccia F., Del Vecchio �., Mariotti E., Di Noto R., Morel A.P., Puisieux A., Salvatore F., Ansieau S. (2014) ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells. Mol Cancer., vol. 13, pp. 213. doi: 10.1186�1476-4598-13-213.
�eontis N.B., Stombaugh �., Westhof E. (2002) The non-Watson- Crick base pairs and their associated isostericity matrices.
Nucleic Acids Research, vol. 30, no. 16, pp. 3497–3531.
�ondin E., �ohera P., Telonisa A.G., Quanna K., et al. (2015) Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. PNAS USA., vol. 112, no. 10, pp. 1106-1115.
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Pastrello C., Polesel �., Della Puppa �., Viel A., Maestro R. (2010) Association between hsa-mir-146a genotype and tumor age- of-onset in BRCA1�BRCA2-negative familial breast and ovarian cancer patients. Carcinogenesis, vol. 31, no. 12, pp. 2124-6. doi: 10.1093�carcin�bgq184.
Peurala H., Greco D., Heikkinen T., Kaur S., Bartkova �., �amshidi M., Aittomäki K., Heikkilä P., Bartek �., Blomqvist C., Büt- zow R., Nevanlinna H. (2011) MiR-34a expression has an effect for lower risk of metastasis and associates with expression patterns predicting clinical outcome in breast cancer. P�oS �ne, vol. 6, no. 11, pp. e26122. doi:10.1371�journal.pone.0026122.
Ray A., Ray B.K. (2015) Induction of Ras by SAF-1�MAZ through a feed-forward loop promotes angiogenesis in breast cancer.
Cancer Med, vol. 4, no. 2, pp. 224-34. doi: 10.1002�cam4.362.
Wang C., Zheng X., Shen C., Shi �. (2012) MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and �ASP1 in human triple-negative breast cancer cells. � Exp Clin Cancer Res., vol. 31, pp. 58. doi: 10.1186�1756-9966-31-58.
Banin Hirata B.K., �da �.M., �osi Guembarovski R., Ariza C.B., de �liveira C.E., Watanabe M.A. Molecular markers for breast cancer: prediction on tumor behavior �� Dis Markers. – 2014. – Vol. 2014. – P. 513158. doi: 10.1155�2014�513158.
Barba M., Vici P., Pizzuti �., Di �auro �., Sergi D., Di Benedetto A., Ercolani C., Sperati F., Terrenato I., Botti C., Mentuccia �., Iezzi �., Gamucci T., Natoli C., Vitale I., Mottolese M., De Maria R., Maugeri-Saccà M. Body mass index modifies the relationship between γ-H2AX, a DNA damage biomarker, and pathological complete response in triple-negative breast cancer �� BMC Cancer. – 2017. – Vol. 17, No. 1. – P. 101. doi: 10.1186�s12885-016-3045-z.
Burstein M.D., Tsimelzon A., Poage G.M., Covington K.R., Contreras A., Fuqua S.A., Savage M.I., �sborne C.K., Hilsenbeck S.G., Chang �.C., Mills G.B., �au C.C., Brown P.H. Comprehensive genomic analysis identifies novel subtypes and targets of triple- negative breast cancer �� Clin Cancer Res. – 2015. – Vol. 21, No. 7. – P. 1688-98. doi: 10.1158�1078-0432.CCR-14-0432.
Chakraborty C., Chin K.�., Das S. miRNA-regulated cancer stem cells: understanding the property and the role of miRNA in carcinogenesis �� Tumour Biol. – 2016. – Vol. 37, No. 10. – P. 13039-13048. PMID: 27468722
Chaudhary S., Krishna B.M., Mishra S.K. A novel F�XA1�ESR1 interacting pathway: A study of �ncomine breast cancer mi- croarrays �� �ncol �ett. – 2017. – Vol. 14, No. 2. – P. 1247-1264. doi: 10.3892�ol.2017.6329.
Chistiakov D.A., �rekhov A.N., Bobryshev �.V. MicroRNA regulation of macrophages in human pathologies �� � Mol Cell Cardiol. – 2016. – Vol. 94. – P. 107-121. doi: 10.1016�j.yjmcc.2016.03.015
Cicatiello �., Mutarelli M., Grober �.M., Paris �., Ferraro �., Ravo M., Tarallo R., �uo S., Schroth G.P., Seifert M., Zinser C., Chiusano M.�., Traini A., De Bortoli M., Weisz A. Estrogen receptor alpha controls a gene network in luminal-like breast cancer cells comprising multiple transcription factors and microRNAs �� Am � Pathol. – 2010. – Vol. 176, No. 5. – P. 2113-30. doi: 10.2353� ajpath.2010.090837.
Donepudi M.S., Kondapalli K., Amos S.�., Venkanteshan P. Breast cancer statistics and markers �� � Cancer Res Ther. – 2014. – Vol. 10, No. 3. – P. 506-11. doi: 10.4103�0973-1482.137927.
Fasching P.A., �oibl S., Hu C., Hart S.N., Shimelis H., Moore R., Schem C., Tesch H., Untch M., Hilfrich �., Rezai M., Gerber B., Costa S.D., Blohmer �.U., Fehm T., Huober �., �iedtke C., Weinshilboum R.M., Wang �., Ingle �.N., Müller V., Nekljudova V., Weber K.E., Rack B., Rübner M., von Minckwitz G., Couch F.�. BRCA1�2 Mutations and Bevacizumab in the Neoadjuvant Treat- ment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study �� � Clin �ncol. – 2018. – P. �C�2017772285. doi: 10.1200��C�.2017.77.2285.
Feldinger K., Generali D., Kramer-Marek G., Gijsen M., Ng T.B., Wong �.H., Strina C., Cappelletti M., Andreis D., �i �.�., Bridges E., Turley H., �eek R., Roxanis I., Capala �., Murphy G., Harris A.�., Kong A. ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer �� �ncotarget. – 2014. – Vol. 5, No. 16. – P. 6633-46.
Hamam R., Ali A.M., Alsaleh K.A., Kassem M., Alfayez M., Aldahmash A., Alajez N.M. microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection �� Sci Rep. – 2016. – Vol. 6. – P. 25997. doi:10.1038�srep25997.
Healy N.A., Heneghan H.M., Miller N., �sborne C.K., Schiff R., Kerin M.�. Systemic mirnas as potential biomarkers for ma- lignancy �� Int � Cancer. – 2012. – Vol. 131, No. 10. – P. 2215-22. doi: 10.1002�ijc.27642.
Howe E.N., Cochrane D.R., Richer �.K. Targets of miR-200c mediate suppression of cell motility and anoikis resistance �� Breast Cancer Res. – 2011. – Vol. 13, No. 2. – P. R45. doi:10.1186�bcr2867.
Hsieh T.H., Hsu C.�., Tsai C.F., �ong C.�., Chai C.�., Hou M.F., �ee �.N., Wu D.C., Wang S.C., Tsai E.M. miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis �� �ncotarget. – 2015. – Vol. 6, No. 1. – P. 494-509. PMID: 25504437
Ivashchenko A., Berillo �., Pyrkova A., Niyazova R., Atambayeva Sh. The properties of binding sites of miR-619-5p, miR- 5095, miR-5096 and miR-5585-3p in the mRNAs of human genes �� Biomed Research International. – 2014. – Vol. 2014. – P. e8.
Ivashchenko A., Berillo �., Pyrkova A., Niyazova R. Binding Sites of miR-1273 Family on the mRNA of Target Genes �� Biomed Research International. – 2014. – Vol. 2014. – P. e11.
Ivashchenko A.T., Pyrkova A.�., Niyazova R.�., Alybayeva A., Baskakov K. Prediction of miRNA binding sites in mRNA �� Bioinformation. – 2016. – Vol. 12, No. 4. – P. 237-240.
�in �., Wessely �., Marcusson E.G., Ivan C., Calin G.A., Alahari S.K. Prooncogenic factors miR-23b and miR-27b are regu- lated by Her2�Neu, EGF, and TNF-α in breast cancer �� Cancer Res. – 2013. – Vol. 73, No. 9. – P. 2884-96. doi: 10.1158�0008-5472. CAN-12-2162.
�in �., Zhao M., Xie Q., Zhang H., Wang Q., Ma Q. MicroRNA-338-3p functions as tumor suppressor in breast cancer by target- ing S�X4 �� Int � �ncol. – 2015. – Vol. 47, No. 4. – P. 1594-602. doi: 10.3892�ijo.2015.3114.
�ohnson �., Thijssen B., McDermott U., Garnett M., Wessels �.F., Bernards R. Targeting the RB-E2F pathway in breast cancer
�� �ncogene. – 2016. – Vol. 35, No. 37. – P. 4829-35. doi: 10.1038�onc.2016.32.
Kool E.T. Hydrogen bonding, base stacking, and steric effects in DNA replication �� Annual Review of Biophysics and Biomo- lecular Structure. – 2001. – Vol.30. – P. 1–22.
�eccia F., Del Vecchio �., Mariotti E., Di Noto R., Morel A.P., Puisieux A., Salvatore F., Ansieau S. ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells �� Mol Cancer. – 2014. – Vol. 13. – P. 213. doi: 10.1186�1476-4598-13-213.
�eontis N.B., Stombaugh �., Westhof E. The non-Watson- Crick base pairs and their associated isostericity matrices �� Nucleic Acids Research. – 2002. – Vol. 30, No. 16. – P. 3497–3531.
�ondin E., �ohera P., Telonisa A.G., Quanna K., et al. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs �� PNAS USA. – 2015. – Vol. 112, No. 10. – P. 1106-1115.
Madoux F., Dreymuller D., Pettiloud �.P., Santos R., Becker-Pauly C., �udwig A., Fields G.B., Bannister T., Spicer T.P., Cudic M., Scampavia �.D., Minond D. Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite-binding glycosylated substrate �� Sci Rep. – 2016. – Vol. 6, No. 1, P. 11. doi: 10.1038�s41598-016-0013-4.
Pastrello C., Polesel �., Della Puppa �., Viel A., Maestro R. Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1�BRCA2-negative familial breast and ovarian cancer patients �� Carcinogenesis. – 2010. – Vol. 31, No. 12. – P. 2124-6. doi: 10.1093�carcin�bgq184.
Peurala H., Greco D., Heikkinen T., Kaur S., Bartkova �., �amshidi M., Aittomäki K., Heikkilä P., Bartek �., Blomqvist C., Bützow R., Nevanlinna H. MiR-34a expression has an effect for lower risk of metastasis and associates with expression patterns predicting clinical outcome in breast cancer �� P�oS �ne. – 2011. – Vol. 6, No. 11. – P. e26122. doi:10.1371�journal.pone.0026122. Ray A., Ray B.K. Induction of Ras by SAF-1�MAZ through a feed-forward loop promotes angiogenesis in breast cancer �� Can-
cer Med. – 2015. – Vol. 4, No. 2. – P. 224-34. doi: 10.1002�cam4.362.
Wang C., Zheng X., Shen C., Shi �. MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and �ASP1 in human triple-negative breast cancer cells �� � Exp Clin Cancer Res. – 2012. – Vol. 31. – P. 58. doi: 10.1186�1756-9966-31-58.
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Feldinger K., Generali D., Kramer-Marek G., Gijsen M., Ng T.B., Wong �.H., Strina C., Cappelletti M., Andreis D., �i �.�., Bridges E., Turley H., �eek R., Roxanis I., Capala �., Murphy G., Harris A.�., Kong A. (2014) ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer. �ncotarget, vol. 5, no. 16, pp. 6633-46.
Hamam R., Ali A.M., Alsaleh K.A., Kassem M., Alfayez M., Aldahmash A., Alajez N.M. (2016) microRNA expression profiling on individual breast cancer patients identifies novel panel of circulating microRNA for early detection. Sci Rep., vol. 6, pp. 25997. doi:10.1038�srep25997.
Healy N.A., Heneghan H.M., Miller N., �sborne C.K., Schiff R., Kerin M.�. (2012) Systemic mirnas as potential biomarkers for malignancy. Int � Cancer, vol. 131, no. 10, pp. 2215-22. doi: 10.1002�ijc.27642.
Howe E.N., Cochrane D.R., Richer �.K. (2011) Targets of miR-200c mediate suppression of cell motility and anoikis resistance.
Breast Cancer Res., vol. 13, no. 2, pp. R45. doi:10.1186�bcr2867.
Hsieh T.H., Hsu C.�., Tsai C.F., �ong C.�., Chai C.�., Hou M.F., �ee �.N., Wu D.C., Wang S.C., Tsai E.M. (2015) miR-125a- 5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis. �ncotarget, vol. 6, no. 1, pp. 494-509. PMID: 25504437
Ivashchenko A., Berillo �., Pyrkova A., Niyazova R., Atambayeva Sh. (2014) The properties of binding sites of miR-619-5p, miR-5095, miR-5096 and miR-5585-3p in the mRNAs of human genes. Biomed Research International, vol. 2014, pp. e8.
Ivashchenko A., Berillo �., Pyrkova A., Niyazova R. (2014) Binding Sites of miR-1273 Family on the mRNA of Target Genes.
Biomed Research International, vol. 2014, pp. e11.
Ivashchenko A.T., Pyrkova A.�., Niyazova R.�., Alybayeva A., Baskakov K. (2016) Prediction of miRNA binding sites in mRNA. Bioinformation, vol. 12, no. 4, pp. 237-240.
�in �., Wessely �., Marcusson E.G., Ivan C., Calin G.A., Alahari S.K. (2013) Prooncogenic factors miR-23b and miR-27b are regulated by Her2�Neu, EGF, and TNF-α in breast cancer. Cancer Res., vol. 73, no. 9, pp. 2884-96. doi: 10.1158�0008-5472.CAN- 12-2162.
�in �., Zhao M., Xie Q., Zhang H., Wang Q., Ma Q. (2015) MicroRNA-338-3p functions as tumor suppressor in breast cancer by targeting S�X4. Int � �ncol., vol. 47, no. 4, pp. 1594-602. doi: 10.3892�ijo.2015.3114.
�ohnson �., Thijssen B., McDermott U., Garnett M., Wessels �.F., Bernards R. (2016) Targeting the RB-E2F pathway in breast cancer, �ncogene, vol. 35, no. 37, pp. 4829-35. doi: 10.1038�onc.2016.32.
Kool E.T. (2001) Hydrogen bonding, base stacking, and steric effects in DNA replication. Annual Review of Biophysics and Biomolecular Structure, vol.30, pp. 1–22.
�eccia F., Del Vecchio �., Mariotti E., Di Noto R., Morel A.P., Puisieux A., Salvatore F., Ansieau S. (2014) ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells. Mol Cancer., vol. 13, pp. 213. doi: 10.1186�1476-4598-13-213.
�eontis N.B., Stombaugh �., Westhof E. (2002) The non-Watson- Crick base pairs and their associated isostericity matrices.
Nucleic Acids Research, vol. 30, no. 16, pp. 3497–3531.
�ondin E., �ohera P., Telonisa A.G., Quanna K., et al. (2015) Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. PNAS USA., vol. 112, no. 10, pp. 1106-1115.
Madoux F., Dreymuller D., Pettiloud �.P., Santos R., Becker-Pauly C., �udwig A., Fields G.B., Bannister T., Spicer T.P., Cudic M., Scampavia �.D., Minond D. (2016) Discovery of an enzyme and substrate selective inhibitor of ADAM10 using an exosite- binding glycosylated substrate. Sci Rep., vol. 6, no. 1, pp. 11. doi: 10.1038�s41598-016-0013-4.
Pastrello C., Polesel �., Della Puppa �., Viel A., Maestro R. (2010) Association between hsa-mir-146a genotype and tumor age- of-onset in BRCA1�BRCA2-negative familial breast and ovarian cancer patients. Carcinogenesis, vol. 31, no. 12, pp. 2124-6. doi: 10.1093�carcin�bgq184.
Peurala H., Greco D., Heikkinen T., Kaur S., Bartkova �., �amshidi M., Aittomäki K., Heikkilä P., Bartek �., Blomqvist C., Büt- zow R., Nevanlinna H. (2011) MiR-34a expression has an effect for lower risk of metastasis and associates with expression patterns predicting clinical outcome in breast cancer. P�oS �ne, vol. 6, no. 11, pp. e26122. doi:10.1371�journal.pone.0026122.
Ray A., Ray B.K. (2015) Induction of Ras by SAF-1�MAZ through a feed-forward loop promotes angiogenesis in breast cancer.
Cancer Med, vol. 4, no. 2, pp. 224-34. doi: 10.1002�cam4.362.
Wang C., Zheng X., Shen C., Shi �. (2012) MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and �ASP1 in human triple-negative breast cancer cells. � Exp Clin Cancer Res., vol. 31, pp. 58. doi: 10.1186�1756-9966-31-58.
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Как цитировать
Aisina, D., Niyazova, R., Atambayeva, S., Imyanitov, E., & Ivashchenko, A. (2018). Характеристики взаимодействия miRNA C 5’UTR, CDS, 3’UTR mRNA кандидатных генов субтипов рака молочной железы. Вестник КазНУ. Серия биологическая, 75(2), 30–48. https://doi.org/10.26577/eb-2018-2-1326
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МОЛЕКУЛЯРНАЯ БИОЛОГИЯ И ГЕНЕТИКА
