Epigenetic alterations in patients with cervical intraepithelial neoplasia

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Resumo

Despite numerous basic studies on the issues of malignant degeneration of precancerous diseases of the cervix and the widespread introduction of screening programs, mortality from cervical cancer continues to take the leading positions. Currently, there are no reliable prognostic criteria for malignancy of squamous cervical intraepithelial neoplasia (CIN).

The results of recent studies indicated that epigenetic regulation of gene expression plays a fundamental role in the pathogenesis of numerous malignant neoplasms including cervical cancer. The analysis of the literature data showed that squamous cell metaplasia in the cervical transformation zone is affected by cholinergic signaling. Acetylcholine and its receptors do not only regulate the processes of inflammation and proliferation of the normal cells, but they also play an important role in response to oncological processes by increasing the expression of certain receptor subunits, they inhibit apoptosis and increase the likelihood of metastasis. Thus, epigenetic modifications associated with dysplastic and metaplastic processes can serve as a powerful tool for risk stratification, prediction and treatment of cervical neoplasms caused by human papillomavirus (HPV).

Conclusion: The development of a panel of molecular predictors for accurate differential diagnosis of the degree of lesion, as well as identification of the risk group for the transition of dysplasia to cancer, will improve the examination algorithms and make it possible to timely initiate pathogenetic therapy in patients with HPV-associated cervical diseases.

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Sobre autores

Sergey Levakov

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: levakoff@yandex.ru
ORCID ID: 0000-0002-4591-838X

Dr. Med. Sci., Professor, Head of the Department of Obstetrics and Gynecology, N.V. Sklifosovsky ICM

Rússia, Moscow

Makhluga Dzhafarova

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: qoqlu55@mail.ru

PhD student of the Department of Obstetrics and Gynecology, N.V. Sklifosovsky ICM

Rússia, Moscow

Mariami Kaviladze

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Autor responsável pela correspondência
Email: mariam-kaviladze@mail.ru
ORCID ID: 0000-0003-0221-5673

PhD student, Teaching Assistant at the Department of Obstetrics and Gynecology, N.V. Sklifosovsky ICM

Rússia, Moscow

Shirin Guseynova

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: guseinova.shirin@mail.ru
ORCID ID: 0009-0008-6967-7497

Student, N.V. Sklifosovsky ICM

Rússia, Moscow

Diana Mushkyurova

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia

Email: dr.ramazanovna@gmail.com
ORCID ID: 0009-0007-7494-5807

PhD student of the Department of Obstetrics and Gynecology, N.V. Sklifosovsky ICM

Rússia, Moscow

Bibliografia

  1. Calleja-Macias I.E., Kalantari M., Bernard H.U. Cholinergic signaling through nicotinic acetylcholine receptors stimulates the proliferation of cervical cancer cells: an explanation for the molecular role of tobacco smoking in cervical carcinogenesis? Int. J. Cancer. 2009; 124(5): 1090-6. https://dx.doi.org/ 10.1002/ijc.24053.
  2. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021; 71(3): 209-49. https://dx.doi.org/10.3322/caac.21660.
  3. Dudea-Simon M., Mihu D., Pop L.A., Ciortea R., Malutan A.M., Diculescu D. et al. Alteration of gene and miRNA expression in cervical intraepithelial neoplasia and cervical cancer. Int. J. Mol. Sci. 2022; 23(11): 6054. https://dx.doi.org/10.3390/ ijms23116054.
  4. Liu Y., Qian J., Sun Z., Zhangsun D., Luo S. Cervical cancer correlates with the differential expression of nicotinic acetylcholine receptors and reveals therapeutic targets. Mar. Drugs. 2019; 17(5): 256. https://dx.doi.org/ 10.3390/md17050256.
  5. Gius D., Funk M.C., Chuang E.Y., Feng S., Huettner P.C., Nguyen L. et al. Profiling microdissected epithelium and stroma to model genomic signatures for cervical carcinogenesis accommodating for covariates. Cancer Res. 2007; 67: 7113-23. https://dx.doi.org/ 10.1158/0008-5472.CAN-07-0260.
  6. Graham S.V. Keratinocyte differentiation-dependent human papillomavirus gene regulation. Viruses. 2017; 9(9): 245. https://dx.doi.org/10.3390/v9090245.
  7. Zhang L., Wu J., Ling M.T., Zhao L., Zhao K.N. The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses. Mol. Cancer. 2015; 14: 87. https://dx.doi.org/10.1186/s12943-015-0361-x.
  8. 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. https://dx.doi.org/10.1016/0092-8674(90)90409-8.
  9. Münger K., Basile J.R., Duensing S., Eichten A., Gonzalez S.L., Grace M. et al. Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene. 2001; 20(54): 7888-98. https://dx.doi.org/10.1038/sj.onc.1204860.
  10. Botezatu A., Iancu I.V., Plesa A., Manda D., Popa O., Bostan M. et al. Methylation of tumour suppressor genes associated with thyroid cancer. Cancer Biomark. 2019; 25(1): 53-65. https://dx.doi.org/10.3233/CBM-182265.
  11. Chabeda A., Yanez R.J.R., Lamprecht R., Meyers A.E., Rybicki E.P, Hitzeroth I.I. Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Res. 2018; 5: 46-58. https://dx.doi.org/10.1016/j.pvr.2017.12.006.
  12. Wentzensen N., Sherman M.E., Schiffman M., Wang S.S. Utility of methylation markers in cervical cancer early detection: appraisal of the state-of-the-science. Gynecol. Oncol. 2009; 112(2): 293-9. https://dx.doi.org/10.1016/j.ygyno.2008.10.012.
  13. Fang J., Zhang H., Jin S. Epigenetics and cervical cancer: from pathogenesis to therapy. Tumour Biol. 2014; 35(6): 5083-93. https://dx.doi.org/10.1007/s13277-014-1737-z.
  14. Zhao X., Cui Y., Li Y., Liang S., Zhang Y., Xie L. et al. [Significance of TSLC1 gene methylation and TSLC1 protein expression in the progression of cervical lesions]. Zhonghua Zhong Liu Za Zhi. 2015; 37(5): 356-60. Chinese.
  15. Laengsri V., Kerdpin U., Plabplueng C., Treeratanapiboon L., Nuchnoi P. Cervical cancer markers: epigenetics and microRNAs. Lab. Med. 2018; 49(2): 97-111. https://dx.doi.org/10.1093/labmed/lmx080.
  16. Tornesello M.L., Faraonio R., Buonaguro L., Annunziata C., Starita N., Cerasuolo A. et al. The role of microRNAs, long non-coding RNAs, and circular RNAs in cervical cancer. Front. Oncol. 2020; 10:150. https://dx.doi.org/10.3389/fonc.2020.00150.
  17. Lui W.O., Pourmand N., Patterson B.K., Fire A. Patterns of known and novel small RNAs in human cervical cancer. Cancer Res. 2007; 67(13): 6031-43. https://dx.doi.org/10.1158/0008-5472.CAN-06-0561.
  18. Pardini B., De Maria D., Francavilla A., Di Gaetano C., Ronco G., Naccarati A. MicroRNAs as markers of progression in cervical cancer: a systematic review. BMC Cancer. 2018; 18(1): 696. doi: 10.1186/s12885-018-4590-4.
  19. He Y., Lin J., Ding Y., Liu G., Luo Y., Huang M. et al. A systematic study on dysregulated microRNAs in cervical cancer development. Int. J. Cancer. 2016; 138(6): 1312-27. doi: 10.1002/ijc.29618.
  20. Wang X., Wang H.K., McCoy J.P., Banerjee N.S., Rader J.S., Broker T.R. et al. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA. 2009; 15(4): 637-47. https://dx.doi.org/10.1261/rna.1442309.
  21. Aalijahan H., Ghorbian S. Long non-coding RNAs and cervical cancer. Exp. Mol. Pathol. 2019; 106: 7-16. https://dx.doi.org/10.1016/j.yexmp.2018.11.010.
  22. Kim H.J., Lee D.W., Yim G.W., Nam E.J., Kim S., Kim S.W. et al. Long non-coding RNA HOTAIR is associated with human cervical cancer progression. Int. J. Oncol. 2015; 46(2): 521-30. doi: 10.3892/ijo.2014.2758.
  23. Jiang Y., Li Y., Fang S., Jiang B., Qin C., Xie P. et al. The role of MALAT1 correlates with HPV in cervical cancer. Oncol. Lett. 2014; 7(6): 2135-41. https://dx.doi.org/10.3892/ol.2014.1996.
  24. Wessler I., Kirkpatrick C.J. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br. J. Pharmacol. 2008; 154(8): 1558-71. https://dx.doi.org/10.1038/bjp.2008.185.
  25. Bierut L.J. Nicotine dependence and genetic variation in the nicotinic receptors. Drug Alcohol Depend. 2009; 104 Suppl 1(Suppl 1): S64-9. https://dx.doi.org/10.1016/j.drugalcdep.2009.06.003.
  26. Cheng K., Samimi R., Xie G., Shant J., Drachenberg C., Wade M. et al. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation. Am. J. Physiol. Gastrointest. Liver Physiol. 2008; 295(3): G591-7. https://dx.doi.org/10.1152/ajpgi.00055.2008.
  27. Pettersson A., Nylund G., Khorram-Manesh A., Nordgren S., Delbro D.S. Nicotine induced modulation of SLURP-1 expression in human colon cancer cells. Auton. Neurosci. 2009; 148(1-2): 97-100. https://dx.doi.org/10.1016/j.autneu.2009.03.002.
  28. Song P., Sekhon H.S., Jia Y., Keller J.A., Blusztajn J.K., Mark G.P. et al. Acetylcholine is synthesized by and acts as an autocrine growth factor for small cell lung carcinoma. Cancer Res. 2003; 63(1): 214-21.
  29. Cuny H., Yu R., Tae H.S., Kompella S.N., Adams D.J. α-Conotoxins active at α3-containing nicotinic acetylcholine receptors and their molecular determinants for selective inhibition. Br. J. Pharmacol. 2018; 175(11): 1855-68. https://dx.doi.org/10.1111/bph.13852.
  30. Chen C.S., Lee C.H., Hsieh C.D., Ho C.T., Pan M.H., Huang C.S. et al. Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins. Breast Cancer Res. Treat. 2011; 125(1): 73-87. https://dx.doi.org/10.1007/s10549-010-0821-3.
  31. Sun H., Ma X. α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells. Exp. Toxicol. Pathol. 2015; 67(9): 477-82. https://dx.doi.org/10.1016/j.etp.2015.07.001.
  32. Tu S.H., Ku C.Y., Ho C.T., Chen C.S., Huang C.S., Lee C.H. et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced α9-nicotinic acetylcholine receptor upregulation in human breast cancer cells. Mol. Nutr. Food Res. 2011; 55(3): 455-66. https://dx.doi.org/10.1002/mnfr.201000254.
  33. Trombino S., Cesario A., Margaritora S., Granone P., Motta G., Falugi C. et al. Alpha7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen-activated protein kinase pathway. Cancer Res. 2004; 64(1): 135-45. https://dx.doi.org/10.1158/0008-5472.can-03-1672.
  34. Jia Y., Sun H., Wu H., Zhang H., Zhang X., Xiao D. et al. Nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR/AKT signaling in human gastric cancer cells. PLoS One. 2016; 11(2): e0149120. https://dx.doi.org/10.1371/journal.pone.0149120.
  35. Liu K., Liu Y., Yu Y., Feng T., Zhang S. Identification of acetylcholine-related enzymes and the role of acetylcholine and nicotine in human cervical cancer. Int. J. Clin. Exp. Pathol. 2016; 9(4): 4854-61.
  36. Calleja-Macias I.E., Kalantari M., Bernard H.U. Cholinergic signaling through nicotinic acetylcholine receptors stimulates the proliferation of cervical cancer cells: an explanation for the molecular role of tobacco smoking in cervical carcinogenesis? Int. J. Cancer. 2009; 124(5): 1090-6. https://dx.doi.org/10.1002/ijc.24053.
  37. Smedlund K., Tano J.Y., Margiotta J., Vazquez G. Evidence for operation of nicotinic and muscarinic acetylcholine receptor-dependent survival pathways in human coronary artery endothelial cells. J. Cell. Biochem. 2011; 112(8): 1978-84. https://dx.doi.org/10.1002/jcb.23169.
  38. Li D.J., Fu H., Tong J., Li Y.H, Qu L.F., Wang P. et al Cholinergic anti-inflammatory pathway inhibits neointimal hyperplasia by suppressing inflammation and oxidative stress. Redox. Biol. 2018; 15: 22-33. https://dx.doi.org/10.1016/j.redox.2017.11.013.
  39. Arredondo J., Chernyavsky A.I., Jolkovsky D.L., Pinkerton K.E., Grando S.A. Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of alpha7 nicotinic receptor in oral keratinocytes. FASEB J. 2006; 20(12): 2093-101. https://dx.doi.org/10.1096/fj.06-6191com.
  40. Nakayama H., Numakawa T., Ikeuchi T. Nicotine-induced phosphorylation of Akt through epidermal growth factor receptor and Src in PC12h cells. J. Neurochem. 2002; 83(6): 1372-9. https://dx.doi.org/10.1046/j.1471-4159.2002.01248.x.
  41. Vieira-Alves I., Coimbra-Campos L.M.C., Sancho M., da Silva R.F., Cortes S.F., Lemos V.S. Role of the α7 nicotinic acetylcholine receptor in the pathophysiology of atherosclerosis. Front Physiol. 2020; 11: 621769. https://dx.doi.org/10.3389/fphys.2020.621769.
  42. Шулепко М.А., Бычков М.Л., Кульбацкий Д.С., Люкманова Е.Н. Никотиновые ацетилхолиновые рецепторы человека. Часть II: Не-нейрональная холинергическая система. Биоорганическая химия. 2019; 45(3): 227-37. [Shulepko M.A., Kulbatskii D.S., Bychkov M.L., Lyukmanova E.N. Human nicotinic acetylcholine receptors: Part II. Non-neuronal cholinergic system. Russian Journal of Bioorgfnic Chemistry. 2019; 45(3): 227-37. https://dx.doi.org/10.1134/S0132342319020131.
  43. Prokopczyk B., Cox J.E., Hoffmann D., Waggoner S.E. Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J. Natl. Cancer Inst. 1997; 89(12): 868-73. https://dx.doi.org/10.1093/jnci/89.12.868.
  44. Fonseca-Moutinho J.A. Smoking and cervical cancer. ISRN Obstet. Gynecol. 2011; 2011: 847684. https://dx.doi.org/10.5402/2011/847684.
  45. Jensen K.E., Schmiedel S., Frederiksen K., Norrild B., Iftner T., Kjær S.K. Risk for cervical intraepithelial neoplasia grade 3 or worse in relation to smoking among women with persistent human papillomavirus infection. Cancer Epidemiol. Biomarkers Prev. 2012; 21(11):1949-55. https://dx.doi.org/10.1158/1055-9965.EPI-12-0663.

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