Differential diagnosis of cervical intraepithelial neoplasia of varying severity via quantitative assessment of anti-oncogenic microRNA expression
Objective. To estimate the possibility of differential diagnosis of the severity of cervical neoplasia, by quantitatively assessing the expression of the anti-oncogenic microRNAs, such as has-mir-143*-3p, has-mir-145*-3p, has-mir-199a-5p, and has-mir-122-5p, in the cervical epithelial scrapings.Karnaukhov V.N., Faizullin L.Z., Nazarova N.M., Mzarelua G.M., Bairamova G.R., Chernova V.F., Faizullin A.L., Kozachenko A.V., Trofimov D.Yu., Prilepskaya V.N., Sukhikh G.T.
Subjects and methods. The investigation enrolled 101 women aged 18 to 49 years (mean age, 32.7±0.5 years) who were divided into 4 groups: 1) 30 patients without cervical lesions; 2) 32 with low-grade squamous intraepithelial lesion (LSIL); 3) 26 with high-grade squamous intraepithelial lesions (HSIL); 4) 13 with cancer of cervix uteri CCU).
Clinical diagnosis was established by cytological and histological studies and extended colposcopy. Quantitative real-time PCR was used to test for human papillomavirus and to measure miRNA expression lesions.
Results. The synthesis of anti-oncogenic microRNAs, such as mir-143, mir-145, and mir-199, considerably reduced in the epithelium of the cervix uteri in its neoplastic lesions. At the same time, the expression of mir-143 and mir-145 was reduced in proportion to the severity of a lesion – the minimum expression level was observed in CCU. The expression rates of both separate microRNAs and the total expression rate of two (mir-143 and mir-145) or three (mir-143, mir-145, and mir-199) microRNAs in the cervical scrapings allowed differentiation of women with low-grade and high-grade intraepithelial hyperplasia and those with CCU.
Conclusion. This study permits the expression level of miRNAs, such as mir-143, mir-145, and mir-199, along with traditional methods, to be considered as an informative molecular marker to predict the extent of involvement of the cervical epithelium in neoplastic cervical diseases.
Keywords
cervical intraepithelial neoplasia
cervical cancer
liquid-based cytology
mir-143
mir-145
mir-199
mir-122
expression
Supplementary Materials
- Table 1. Characteristics of the studied microRNAs
- Table 2. The level of microRNA expression in the cervical epithelium is normal, with cervical neoplasia and cervical cancer
References
1. Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D. Global cancer statistics. CA Cancer J. Clin. 2011; 61(2): 69-90.
2. Davydov M.I., Aksel E.M., ed. Statistics of malignant neoplasms in Russia and the CIS countries in 2012. Moscow: Publishing group RONTS; 2014: 47. (in Russian)
3. Seoud M., Tjalma W.A., Ronsse V. Cervical adenocarcinoma: moving towards better prevention. Vaccine. 2011; 29(49): 9148-58.
4. Knoff J., Yang B., Hung C.F., Wu T.C. Cervical cancer: development of targeted therapies beyond molecular pathogenesis. Curr. Obstet. Gynecol. Rep. 2014; 3(1): 18-32.
5. Scheffner M., Werness B.A., Huibregtse J.M., Levine A.J., Howley P.M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990; 63(6): 1129-36.
6. Roman A., Munger K. The papillomavirus E7 proteins. Virology. 2013; 445(1-2): 138-68.
7. Stahlhut C., Slack F.J. MicroRNAs and the cancer phenotype: profiling, signatures and clinical implications. Genome Med. 2013; 5(12): 111.
8. Frixa T., Donzelli S., Blandino G. Oncogenic microRNAs: key players in malignant transformation. Cancers (Basel). 2015; 7(4): 2466-85.
9. Wang F., Li B., Xie X. The roles and clinical significance of microRNAs in cervical cancer. Histol. Histopathol. 2016; 31(2): 131-9.
10. Galamb Á., Benczik M., Zinner B., Vígh E., Baghy K., Jeney C. et al. Dysregulation of microRNA expression in human cervical preneoplastic and neoplastic lesions. Pathol. Oncol. Res. 2015; 21(3): 503-8.
11. Faizullin L.Z., Karnaukhov V.N., Mzarelua G.M., Chernova V.F. MicroRNA expression in cervical intraepithelial neoplasia and cancer of the cervix uteri. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2015; (9): 27-32. (in Russian)
12. Nassirpour R., Mehta P.P., Yin M.J. miR-122 regulates tumorigenesis in hepatocellular carcinoma by targeting AKT3. PLoS One. 2013; 8: e79655.
13. Ergün S., Ulasli M., Igci Y.Z., Igci M., Kırkbes S., Borazan E. et al. The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer. Mol. Biol. Rep. 2015; 42(2): 497-505.
14. Kent O.A., McCall M.N., Cornish T.C., Halushka M.K. Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res. 2014; 42(12): 7528-38.
15. Akao Y., Nakagawa Y., Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol. Rep. 2006; 16(4): 845-50.
16. Pekow J., Meckel K., Dougherty U., Butun F., Mustafi R., Lim J. et al. Tumor suppressors miRNA-143 and miR-145 and predicted target proteins API5, ERK5, KRAS, and IRS-1 are differentially expressed in proximal and distal colon. Am. J. Physiol. Gastrointest. Liver Physiol. 2015; 308(3): G179-87.
17. Sachdeva M., Mo Y.Y. MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1. Cancer Res. 2010; 70(1):378-87.
18. Filipowicz W., Grosshans H. The liver-specific microRNA miR-122: biology and therapeutic potential. Prog. Drug Res. 2011; 67: 221-38.
Received 31.08.2016
Accepted 02.09.2016
About the Authors
Karnaukhov Vitaliy Nikolaevich, Junior Researcher, Laboratory of Molecular Genetic Methods, Research Center of Obstetrics, Gynecology and Perinatology,Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79167106789. E-mail: v_karnauhov@oparina4.ru
Faizullin Leonid Zakievich, Cand. Sc. (Biology), Leading Researcher, Laboratory of Molecular Genetic Methods, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79167106789. E-mail: l_faizullin@oparina4.ru
Nazarova Niso Mirzoevna, doctor of medical sciences, leading researcher of the scientific and polyclinic department, Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381403. E-mail: n_nazarova@oparina4.ru
Mzarelua Guranda Merabovna, PhD student of the Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381403. E-mail: mzareluag@mail.ru
Bayramova Guldana Raufovna, doctor of medical sciences, head of the clinical work of the scientific and polyclinic department, Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +7909994700. E-mail: g_bairamova@oparina4.ru
Chernova Victoria Fedorovna, PhD student of the Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4
Fayzullin Alexey Leonidovich, a student of the 6th year, I.M. Sechenov First Moscow State Medical University, Center for Innovative Educational Programs„
Medicine of the Future”. E-mail: a.iiepcuk@gmail.com
Kozachenko Andrey Vladimirovich, leading research assistant of the gynecological department, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954387783. E-mail: a_kozachenko@oparina4.ru
Trofimov Dmitriy Yurievich, Doctor of Biological Sciences, Head of the Laboratory of Molecular Genetic Methods, Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79166144922. E-mail: d_trofimov@oparina4.ru
Prilepskaya Vera Nikolaevna, Doctor of Medical Sciences, Deputy Director for Science, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954386934
Sukhikh Gennady Tikhonovich, Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Director of the Research Center of Obstetrics,
Gynecology and Perinatology, Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +74954381800. E-mail: g_sukhikh@oparina4.ru
For citations: Karnaukhov V.N., Faizullin L.Z., Nazarova N.M.,
Mzarelua G.M., Bairamova G.R., Chernova V.F., Faizullin A.L., Kozachenko A.V.,
Trofimov D.Yu., Prilepskaya V.N., Sukhikh G.T. Differential diagnosis of cervical intraepithelial neoplasia of varying severity via quantitative assessment of anti-oncogenic microRNA expression. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (3): 82-8. (in Russian)
http://dx.doi.org/10.18565/aig.2017.3.82-8
Similar Articles
