oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciencesoncotomsk-140Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESЭКСПРЕССИЯ МИКРОРНК В ОПУХОЛЕВОЙ ТКАНИ У БОЛЬНЫХ РАКОМ ГОРТАНИEXPRESSION MICRORNA IN LARYNX CANCERНикитинаЕ. Г.NikitinaE. G.

Никитина Екатерина Геннадьевна - младший научный сотрудник лаборатории онковирусологии Томского НИИ онкологии, младший научный сотрудник Национального исследовательского ТГУ.Телефон: 8 (3822) 512957. E-mail: ekatarinanikitina@gmail.com. SPIN-код автора в РИНЦ: 5350-0040

Nikitina Ekaterina Gennadievna - M.S., Junior Researcher of the Laboratory of Oncovirology, Tomsk Cancer Research Institute; Junior Researcher of Tomsk State University. Phone: +7 3822 51-29-57. E-mail: ekatarinanikitina@gmail.com

ekatarinanikitina@gmail.comЧеремисинаО. В.CheremisinaO. V.

Черемисина Ольга Владимировна, доктор медицинских наук, руководитель эндоскопического отделения.

Телефон: 8 (3822) 418091. E-mail: CheremisinaOV@oncology.tomsk.ru. SPIN-код в РИНЦ: 9579-2691

Cheremisina Olga Vladimirovna - MD., DSc, Professor, Head of the Endoscopy Department of Tomsk Cancer Research Institute. Phone: +7 3822 41-80-91. E-mail: CheremisinaOV@oncology.tomsk.ru

CheremisinaOV@oncology.tomsk.ruБычковВ. А.BychkovV. A.

Бычков Вячеслав Алексеевич, кандидат медицинских наук, старший научный сотрудник лаборатории онковирусологии. Телефон: 8 (3822) 512957. E-mail: va.bych@gmail.com. SPIN-код автора в РИНЦ: 6174-4896

Bychkov Viacheslav Alekseevich - MD., PhD., Senior Researcher of the Laboratory of Oncovirology, Tomsk Cancer Research Institute; Junior Researcher of Tomsk State University. Phone: +7 3822 51-29-57. E-mail: va.bych@gmail.com

va.bych@gmail.comКульбакинД. Е.KulbakinD. E.

Кульбакин Денис Евгеньевич, кандидат медицинских наук, младший научный сотрудник отделения опухолей головы и шеи.Телефон: (3822)418062. E-mail: kulbakin_d@mail.ru. SPIN-код автора в РИНЦ: 3898-9456

Kulbakin Denis Evgenievic - MD., PhD., Junior Researcher of the Head and Neck Department, Tomsk Cancer Research Institute. Phone: +7 3822 41-80-62. E-mail: kulbakin_d@mail.ru

kulbakin_d@mail.ruЧойнзоновЕ. Л.ChoinzonovE. L.

Чойнзонов Евгений Лхамацыренович - академик РАН, доктор медицинских наук, директор.Телефон: (3822)511039. E-mail: nii@oncology.tomsk.ru. SPIN-код автора в РИНЦ: 2240-8730

Choynzonov Evgeny Lhamatsirenovich - MD., Academician of RAN, Professor, Director of Tomsk Cancer Research Institute Phone: +7 3822 51-10-39. E-mail: nii@oncology.tomsk.ru

nii@oncology.tomsk.ruСтегнийВ. Н.StegniyV. N.

Стегний Владимир Николаевич - доктор биологических наук, профессор, руководитель кафедры цитологии и генетики Биологического института. Телефон: 8 (3822) 529752. E-mail: stegniy@ref.tsu.ru. SPIN-код автора в РИНЦ: 5588-5450

Stegniy Vladimir Nikolaevich - MD., DSc, Professor, Head of the Cytology and Genetics Department of Biology Institute of Tomsk State University. Phone: +7 3822 52-97-52. E-mail: stegniy@ref.tsu.ru

stegniy@ref.tsu.ruЛитвяковН. В.LitviakovN. V.

Литвяков Николай Васильевич - доктор биологических наук, заведующий лабораторией онковирусологии Томского НИИ онкологии, старший научный сотрудник. Национального исследовательского ТГУ. Телефон: (3822) 514607. E-mail: nvlitv72@yandex.ru. SPIN-код автора в РИНЦ: 2546-0181

Litviakov Nikolay Vasilievich - MD., DSc, Head of the Laboratory of Oncovirology, Tomsk Cancer Research Institute; Senior Researcher of Tomsk State University. Phone: +7 3822 51-46-07. E-mail: nvlitv72@yandex.ru

nvlitv72@yandex.ruТомский НИИ онкологии, Томск; Национальный исследовательский Томский государственный университет, ТомскРоссияTomsk Cancer Research Institute, Tomsk; Tomsk State University, TomskRussian FederationТомский НИИ онкологии, ТомскРоссияTomsk Cancer Research Institute, TomskRussian FederationНациональный исследовательский Томский государственный университет, ТомскРоссияTomsk State University, TomskRussian Federation201518022016124652Copyright © Никитина Е.Г., Черемисина О.В., Бычков В.А., Кульбакин Д.Е., Чойнзонов Е.Л., Стегний В.Н., Литвяков Н.В., 20162016Никитина Е.Г., Черемисина О.В., Бычков В.А., Кульбакин Д.Е., Чойнзонов Е.Л., Стегний В.Н., Литвяков Н.В.Nikitina E.G., Cheremisina O.V., Bychkov V.A., Kulbakin D.E., Choinzonov E.L., Stegniy V.N., Litviakov N.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/140

Изучен аберрантный паттерн экспрессии микроРНК-18а, -21, -155, -200а, -200с, -205, -221, -494 в опухолевой ткани плоскоклеточной карциномы гортани относительно прилежащей нормальной ткани у 46 пациентов. Установлено, что клинико-морфологические параметры не оказывают влияния на экспрессию анализируемых микроРНК. Показана гиперэкспрессия онкогенных микроРНК-21, -155, -205 и гипоэкспрессия онкосупрессорной микроРНК-200а в опухолевой ткани относительно прилежащей неизмененной ткани. Представленные результаты позволяют предполагать существенную роль этих микроРНК в канцерогенезе опухолей гортани.

MicroRNA are nonprotein-coding small ribonucleic acids controlling gene expression at post-transcriptional level. MicroRNA technically could controll 2/3 of human genome. At the present study abnormal expression of microRNA-18а, -21, -155, -200а, -200с, -205, -221, -494 in malignant tissue of squamous cell larynx carcinoma of 46 patients were studied. There was no statistically significant correlation between microRNA expression and pathological characteristics. Our data showed that oncogenic microRNA-21, -155, -205 were overexpressed as well as oncosypression microRNA-200a were underexpressed in larynx cancer compared to adjacent normal epithelium.

рак гортанимикрорнКэкспрессия micrornalarynx cancermicrornaexpressionReferencesAdam L., Zhong M., Choi W., Qi W., Nicoloso M., Arora A., Calin G., Wang H., Siefker-Radtke A., McConkey D. miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy // Clin. Cancer Res. 2009. Vol. 15 (16). P. 5060–5072. doi: 10.1158/1078-0432.CCR-08-2245.Adam L., Zhong M., Choi W., Qi W., Nicoloso M., Arora A., Calin G., Wang H., Siefker-Radtke A., McConkey D. miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy // Clin. Cancer Res. 2009. Vol. 15 (16). P. 5060–5072. doi: 10.1158/1078-0432.CCR-08-2245.Ambros V. The functions of animal microRNAs // Nature. 2004. Vol. 431. (7006). P. 350–355.Ambros V. The functions of animal microRNAs // Nature. 2004. Vol. 431. (7006). P. 350–355.Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function // Cell. 2004. Vol. 116 (2). P. 281–297.Bartel D.P. MicroRNAs: genomics, biogenesis, mechanism, and function // Cell. 2004. Vol. 116 (2). P. 281–297.Bracken C.P., Gregory P.A., Kolesnikoff N., Bert A.G., Wang J., Shannon M.F., Goodall G.J. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesen chymal transition // Cancer Res. 2008. Vol. 68, № 19. P. 7846–7854. doi: 10.1158/0008-5472.CAN-08-1942.Bracken C.P., Gregory P.A., Kolesnikoff N., Bert A.G., Wang J., Shannon M.F., Goodall G.J. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition // Cancer Res. 2008. Vol. 68. № 19. P. 7846–7854. doi: 10.1158/0008-5472.CAN-08-1942.Cao P., Zhou L., Zhang J., Zheng F., Wang H., Ma D., Tian J. Comprehensive expression profiling of microRNAs in laryngeal squamous cell carcinoma // Head Neck. 2013. Vol. 35 (5). P. 720–728. doi: 10.1002/hed.23011.Cao P., Zhou L., Zhang J., Zheng F., Wang H., Ma D., Tian J. Comprehensive expression profiling of microRNAs in laryngeal squamous cell carcinoma // Head Neck. 2013. Vol. 35 (5). P. 720–728. doi: 10.1002/hed.23011.Chang S.S., Jiang W.W., Smith I., Poeta L.M., Begum S., Glazer C., Shan S., Westra W., Sidransky D., Califano J.A. MicroRNA alterations in head and neck squamous cell carcinoma // Intern. J. Cancer. 2008. Vol. 123 (12). P. 2791–2797. doi: 10.1002/ijc.23831.Chang S.S., Jiang W.W., Smith I., Poeta L.M., Begum S., Glazer C., Shan S., Westra W., Sidransky D., Califano J.A. MicroRNA alterations in head and neck squamous cell carcinoma // Intern. J. Cancer. 2008. Vol. 123 (12). P. 2791–2797. doi: 10.1002/ijc.23831.Chen Z., Ma T., Huang C., Hu T., Li J. The Pivotal Role of microR- NA-155 in the Control of Cancer // Journal of Cellular Physiology. 2014. Vol. 229 (5). P. 545–550. doi: 10.1002/jcp.24492.Chen Z., Ma T., Huang C., Hu T., Li J. The Pivotal Role of microR- NA-155 in the Control of Cancer // Journal of Cellular Physiology. 2014. Vol. 229 (5). P. 545–550. doi: 10.1002/jcp.24492.Chu E.A., Kim Y.J. Laryngeal cancer: diagnosis and preoperative work-up // Otolaryngol. Clin. North Am. 2008. Vol. 41 (4). P. 673–695. doi: 10.1016/j.otc.2008.01.016.Chu E.A., Kim Y.J. Laryngeal cancer: diagnosis and preoperative work-up // Otolaryngol. Clin. North Am. 2008. Vol. 41 (4). P. 673–695. doi: 10.1016/j.otc.2008.01.016.Cochrane D.R., Howe E.N., Spoelstra N.S., Richer J.K. Loss of miR-200c: a marker of aggressiveness and chemoresistance in female reproductive cancers // J. Oncol. 2009. Vol. 2010: 821717. doi: 10.1155/2010/821717.Cochrane D.R., Howe E.N., Spoelstra N.S., Richer J.K. Loss of miR-200c: a marker of aggressiveness and chemoresistance in female reproductive cancers // J. Oncol. 2009. Vol. 2010: 821717. doi: 10.1155/2010/821717.Concepcion C.P., Bonetti C., Ventura A. The miR-17-92 family of microRNA clusters in development and disease // Cancer J. 2012. Vol. 18 3). P. 262–267. doi: 10.1097/PPO.0b013e318258b60a.Concepcion C.P., Bonetti C., Ventura A. The miR-17-92 family of microRNA clusters in development and disease // Cancer J. 2012. Vol. 18 (3). P. 262–267. doi: 10.1097/PPO.0b013e318258b60a.Di Martino M.T., Gullà A., Cantafio M.E.G., Lionetti M., Leone E., Amodio N., Guzzi P.H., Foresta U., Conforti F., Cannataro M. In vitro and in vivo anti-tumor activity of miR-221/222 inhibitors in multiple myeloma // Oncotarget. 2013. Vol. 4 (2). P. 242–255.Di Martino M.T., Gullà A., Cantafio M.E.G., Lionetti M., Leone E., Amodio N., Guzzi P.H., Foresta U., Conforti F., Cannataro M. In vitro and in vivo anti-tumor activity of miR-221/222 inhibitors in multiple myeloma // Oncotarget. 2013. Vol. 4 (2). P. 242–255.Esquela-Kerscher A., Slack F.J. Oncomirs – microRNAs with a role in cancer // Nature Rev. Cancer. 2006. Vol. 6 (4). P. 259–269. 13. Feng X., Wang Z., Fillmore R., Xi Y. MiR-200, a new star miRNA in human cancer // Cancer lett. 2014. Vol. 344 (2). P. 166–173. doi: 10.1016/j.canlet.2013.11.004.Esquela-Kerscher A., Slack F.J. Oncomirs – microRNAs with a role in cancer // Nature Rev. Cancer. 2006. Vol. 6 (4). P. 259–269.Gurtan A.M., Sharp P.A. The role of miRNAs in regulating gene expression networks // J. Mol. Biol. 2013. Vol. 425 (19). P. 3582–3600. doi: 10.1016/j.jmb.2013.03.007.Feng X., Wang Z., Fillmore R., Xi Y. MiR-200, a new star miRNA in human cancer // Cancer lett. 2014. Vol. 344 (2). P. 166–173. doi: 10.1016/j.canlet.2013.11.004.Hong L., Han Y., Zhang Y., Zhang H., Zhao Q., Wu K., Fan D. MicroRNA-21: a therapeutic target for reversing drug resistance in cancer // Expert Opin. Ther. Targets. 2013. Vol. 17 (9) P. 1073–1080. doi: 10.1517/14728222.2013.819853.Gurtan A.M., Sharp P.A. The role of miRNAs in regulating gene expression networks // J. Mol. Biol. 2013. Vol. 425 (19). P. 3582–3600. doi: 10.1016/j.jmb.2013.03.007.Hui A.B., Lenarduzzi M., Krushel T., Waldron L., Pintilie M., Shi W., Perez-Ordonez B., Jurisica I., O’Sullivan B., Waldron J. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas // Clin. Cancer Res. 2010. Vol. 16 (4). P. 1129–1139. doi: 10.1158/1078-0432.CCR-09-2166.Hong L., Han Y., Zhang Y., Zhang H., Zhao Q., Wu K., Fan D. MicroRNA-21: a therapeutic target for reversing drug resistance in cancer // Expert Opin. Ther. Targets. 2013. Vol. 17 (9) P. 1073–1080. doi: 10.1517/14728222.2013.819853.Iorio M.V., Croce C.M. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review // EMBO Mol. Med. 2012. Vol. 4 (3). P. 143–159. doi: 10.1002/emmm.201100209.Hui A.B., Lenarduzzi M., Krushel T., Waldron L., Pintilie M., Shi W., Perez-Ordonez B., Jurisica I., O’Sullivan B., Waldron J. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas // Clin. Cancer Res. 2010. Vol. 16 (4). P. 1129–1139. doi: 10.1158/1078-0432.CCR-09-2166.Iyevleva A.G., Kuligina E.S., Mitiushkina N.V., Togo A.V., Miki Y., Imyanitov E.N. High level of miR-21, miR-10b, and miR-31 expression in bilateral vs. unilateral breast carcinomas // Breast Cancer Res. Treat. 2012. Vol. 131 (3). P. 1049–1059. doi: 10.1007/s10549-011-1845-z.Iorio M.V., Croce C.M. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review // EMBO Mol. Med. 2012. Vol. 4 (3). P. 143–159. doi: 10.1002/emmm.201100209.Korpal M., Lee E.S., Hu G., Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2 // J. Biol. Chem. 2008. Vol. 283 (22). P. 14910–14914. doi: 10.1074/jbc.C800074200.Iyevleva A.G., Kuligina E.S., Mitiushkina N.V., Togo A.V., Miki Y., Imyanitov E.N. High level of miR-21, miR-10b, and miR-31 expression in bilateral vs. unilateral breast carcinomas // Breast Cancer Res. Treat. 2012. Vol. 131 (3). P. 1049–1059. doi: 10.1007/s10549-011-1845-z.Krichevsky A.M., Gabriely G. miR-21: a small multi-faceted RNA // J. Cell. Mol. Med. 2009. Vol. 13 (1). P. 39–53. doi: 10.1111/j.1582-4934.2008.00556.x.Korpal M., Lee E.S., Hu G., Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2 // J. Biol. Chem. 2008. Vol. 283 (22). P. 14910–14914. doi: 10.1074/jbc.C800074200. .Löffler D., Brocke-Heidrich K., Pfeifer G., Stocsits C., Hackermüller J., Kretzschmar A.K., Burger R., Gramatzki M., Blumert C., Bauer K., Cvijic H., Ullmann A.K., Stadler P.F., Horn F. Interleukin-6–dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer // Blood. 2007. Vol. 110 (4). P. 1330–1333.Krichevsky A.M., Gabriely G. miR-21: a small multi-faceted RNA // J. Cell. Mol. Med. 2009. Vol. 13 (1). P. 39–53. doi: 10.1111/j.1582-4934.2008.00556.x.Mongroo P.S., Rustgi A.K. The role of the miR-200 family in epithelial-mesenchymal transition // Cancer Biol. Ther. 2010. Vol. 10 (3). P. 219–222.Löffler D., Brocke-Heidrich K., Pfeifer G., Stocsits C., Hackermüller J., Kretzschmar A.K., Burger R., Gramatzki M., Blumert C., Bauer K., Cvijic H., Ullmann A.K., Stadler P.F., Horn F. Interleukin-6 –dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer // Blood. 2007. Vol. 110 (4). P. 1330–1333.Nikitina E., Urazova L., Stegny V. MicroRNAs and human cancer // Exp. Oncol. 2012. Vol. 34 (1). P. 2–8.Löffler D., Brocke-Heidrich K., Pfeifer G., Stocsits C., Hackermüller J., Kretzschmar A.K., Burger R., Gramatzki M., Blumert C., Bauer K., Cvijic H., Ullmann A.K., Stadler P.F., Horn F. Interleukin-6 –dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer // Blood. 2007. Vol. 110 (4). P. 1330–1333.O’Donnell K.A., Wentzel E.A., Zeller K.I., Dang C.V., Mendell J.T. c-Myc-regulated microRNAs modulate E2F1 expression // Nature. 2005. Vol. 435 (7043). P. 839–843.Mongroo P.S., Rustgi A.K. The role of the miR-200 family in epithelial-mesenchymal transition // Cancer Biol. Ther. 2010. Vol. 10 (3). P. 219–222.Park S.-M., Gaur A.B., Lengyel E., Peter M.E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2 // Genes Dev. 2008. Vol. 22. (7). P.894–907. doi: 10.1101/gad.1640608.Mongroo P.S., Rustgi A.K. The role of the miR-200 family in epithelial-mesenchymal transition // Cancer Biol. Ther. 2010. Vol. 10 (3). P. 219–222.Peltier H.J., Latham G.J. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues // RNA. 2008. Vol. 14 (5). P. 844–852. doi: 10.1261/rna.939908.Nikitina E., Urazova L., Stegny V. MicroRNAs and human cancer // Exp. Oncol. 2012. Vol. 34 (1). P. 2–8.Pfaffl M.W. A new mathematical model for relative quantification in real-time RT–PCR // Nucleic Acids Res. 2001. Vol. 29 (9). P. e45-e45.Nikitina E., Urazova L., Stegny V. MicroRNAs and human cancer // Exp. Oncol. 2012. Vol. 34 (1). P. 2–8.Qin A.-Y., Zhang X.-W., Liu L., Yu J.-P., Li H., Wang S.-Z.E., Ren X.-B., Cao S. MiR-205 in cancer: An angel or a devil? // Eur. J. Cell Biol. 2013. Vol. 92. (2). P. 54–60.O’Donnell K.A., Wentzel E.A., Zeller K.I., Dang C.V., Mendell J.T. c-Myc-regulated microRNAs modulate E2F1 expression // Nature. 2005. Vol. 435 (7043). P. 839–843.Ren J., Zhu D., Liu M., Sun Y., Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma // Eur. J. Cancer. 2010. Vol. 46 (18). P. 3409–3416. doi: 10.1016/j.ejca.2010.07.047.O’Donnell K.A., Wentzel E.A., Zeller K.I., Dang C.V., Mendell J.T. c-Myc-regulated microRNAs modulate E2F1 expression // Nature. 2005. Vol. 435 (7043). P. 839–843.Tian L., Zhang J., Ge J., Xiao H., Lu J., Fu S., Liu M., Sun Y. MicroRNA-205 suppresses proliferation and promotes apoptosis in laryngeal squamous cell carcinoma // Med. Oncol. 2014. Vol. 31 (1). P. 785. doi: 10.1007/s12032-013-0785-3.Park S.-M., Gaur A.B., Lengyel E., Peter M.E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2 // Genes Dev. 2008. Vol. 22. (7). P.894–907. doi: 10.1101/gad.1640608.Zamore P.D., Haley B. Ribo-gnome: the big world of small RNAs // Science. 2005. Vol. 309 (5740). P. 1519–1524.Park S.-M., Gaur A.B., Lengyel E., Peter M.E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2 // Genes Dev. 2008. Vol. 22. (7). P.894–907. doi: 10.1101/gad.1640608.Zhou J.-J., Zheng S., Sun L.-F., Zheng L. MicroRNA regulation network in colorectal cancer metastasis // World J. Biol. Chem. 2014. Vol. 5 (3). P. 301. doi: 10.4331/wjbc.v5.i3.301.Peltier H.J., Latham G.J. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues // RNA. 2008. Vol. 14 (5). P. 844–852. doi: 10.1261/rna.939908.Peltier H.J., Latham G.J. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues // RNA. 2008. Vol. 14 (5). P. 844–852. doi: 10.1261/rna.939908.Peltier H.J., Latham G.J. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues // RNA. 2008. Vol. 14 (5). P. 844–852. doi: 10.1261/rna.939908.Pfaffl M.W. A new mathematical model for relative quantification in real-time RT–PCR // Nucleic Acids Res. 2001. Vol. 29 (9). P. e45-e45.Pfaffl M.W. A new mathematical model for relative quantification in real-time RT–PCR // Nucleic Acids Res. 2001. Vol. 29 (9). P. e45-e45.Pfaffl M.W. A new mathematical model for relative quantification in real-time RT–PCR // Nucleic Acids Res. 2001. Vol. 29 (9). P. e45-e45.Pfaffl M.W. A new mathematical model for relative quantification in real-time RT–PCR // Nucleic Acids Res. 2001. Vol. 29 (9). P. e45-e45.Qin A.-Y., Zhang X.-W., Liu L., Yu J.-P., Li H., Wang S.-Z.E., Ren X.-B., Cao S. MiR-205 in cancer: An angel or a devil? // Eur. J. Cell Biol. 2013. Vol. 92. (2). P. 54–60. 29. Ren J., Zhu D., Liu M., Sun Y., Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma // Eur. J. Cancer. 2010. Vol. 46 (18). P. 3409–3416. doi: 10.1016/j.ejca.2010.07.047.Qin A.-Y., Zhang X.-W., Liu L., Yu J.-P., Li H., Wang S.-Z.E., Ren X.-B., Cao S. MiR-205 in cancer: An angel or a devil? // Eur. J. Cell Biol. 2013. Vol. 92. (2). P. 54–60. 29. Ren J., Zhu D., Liu M., Sun Y., Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma // Eur. J. Cancer. 2010. Vol. 46 (18). P. 3409–3416. doi: 10.1016/j.ejca.2010.07.047.Qin A.-Y., Zhang X.-W., Liu L., Yu J.-P., Li H., Wang S.-Z.E., Ren X.-B., Cao S. MiR-205 in cancer: An angel or a devil? // Eur. J. Cell Biol. 2013. Vol. 92. (2). P. 54–60. 29. Ren J., Zhu D., Liu M., Sun Y., Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma // Eur. J. Cancer. 2010. Vol. 46 (18). P. 3409–3416. doi: 10.1016/j.ejca.2010.07.047.Qin A.-Y., Zhang X.-W., Liu L., Yu J.-P., Li H., Wang S.-Z.E., Ren X.-B., Cao S. MiR-205 in cancer: An angel or a devil? // Eur. J. Cell Biol. 2013. Vol. 92. (2). P. 54–60. 29. Ren J., Zhu D., Liu M., Sun Y., Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma // Eur. J. Cancer. 2010. Vol. 46 (18). P. 3409–3416. doi: 10.1016/j.ejca.2010.07.047.Tian L., Zhang J., Ge J., Xiao H., Lu J., Fu S., Liu M., Sun Y. MicroRNA-205 suppresses proliferation and promotes apoptosis in laryngeal squamous cell carcinoma // Med. Oncol. 2014. Vol. 31 (1). P. 785. doi: 10.1007/s12032-013-0785-3.Tian L., Zhang J., Ge J., Xiao H., Lu J., Fu S., Liu M., Sun Y. MicroRNA-205 suppresses proliferation and promotes apoptosis in laryngeal squamous cell carcinoma // Med. Oncol. 2014. Vol. 31 (1). P. 785. doi: 10.1007/s12032-013-0785-3.Tian L., Zhang J., Ge J., Xiao H., Lu J., Fu S., Liu M., Sun Y. MicroRNA-205 suppresses proliferation and promotes apoptosis in laryngeal squamous cell carcinoma // Med. Oncol. 2014. Vol. 31 (1). P. 785. doi: 10.1007/s12032-013-0785-3.Tian L., Zhang J., Ge J., Xiao H., Lu J., Fu S., Liu M., Sun Y. MicroRNA-205 suppresses proliferation and promotes apoptosis in laryngeal squamous cell carcinoma // Med. Oncol. 2014. Vol. 31 (1). P. 785. doi: 10.1007/s12032-013-0785-3.Zamore P.D., Haley B. Ribo-gnome: the big world of small RNAs // Science. 2005. Vol. 309 (5740). P. 1519–1524.Zamore P.D., Haley B. Ribo-gnome: the big world of small RNAs // Science. 2005. Vol. 309 (5740). P. 1519–1524.Zamore P.D., Haley B. Ribo-gnome: the big world of small RNAs // Science. 2005. Vol. 309 (5740). P. 1519–1524.Zamore P.D., Haley B. Ribo-gnome: the big world of small RNAs // Science. 2005. Vol. 309 (5740). P. 1519–1524.Zhou J.-J., Zheng S., Sun L.-F., Zheng L. MicroRNA regulation network in colorectal cancer metastasis // World J. Biol. Chem. 2014. Vol. 5 (3). P. 301. doi: 10.4331/wjbc.v5.i3.301.Zhou J.-J., Zheng S., Sun L.-F., Zheng L. MicroRNA regulation network in colorectal cancer metastasis // World J. Biol. Chem. 2014. Vol. 5 (3). P. 301. doi: 10.4331/wjbc.v5.i3.301.Zhou J.-J., Zheng S., Sun L.-F., Zheng L. MicroRNA regulation network in colorectal cancer metastasis // World J. Biol. Chem. 2014. Vol. 5 (3). P. 301. doi: 10.4331/wjbc.v5.i3.301.Zhou J.-J., Zheng S., Sun L.-F., Zheng L. MicroRNA regulation network in colorectal cancer metastasis // World J. Biol. Chem. 2014. Vol. 5 (3). P. 301. doi: 10.4331/wjbc.v5.i3.301.

The authors declare that there are no conflicts of interest present.