Circular RNAs in Cervical Cancer: What are the Prospects?
https://doi.org/10.24060/2076-3093-2023-13-4-320-329
Abstract
C ervical cancer remains a pressing global health problem, creating a significant health burden for women worldwide. High incidence and mortality rates necessitate further research to unravel its underlying molecular mechanisms and identify new diagnostic and treatment strategies. Recent advances in non-coding RNAs have opened up new avenues for research, including circular RNAs (circRNAs) as molecules that play a multifaceted role in cellular processes. Research into circRNAs revealed their unique structure, characterized by the covalent formation of a closed loop, thereby distinguishing them from their linear counterparts. These circRNAs are involved in regulating various aspects of cell physiology with a particular focus on cell growth and development. Interestingly, circRNAs have context-dependent functions, acting both as promoters and inhibitors of oncogenic processes, depending on the complex cellular environment in which they operate. Recent studies have identified aberrant expression patterns of circRNAs in the context of cervical cancer, implying their key role in the disease development. The different expression profiles of circRNAs associated with cervical cancer offer promising opportunities for early detection, accurate prognosis assessment, and personalized treatment strategies. The presented comprehensive review offers an in-depth study of cervical cancer-associated circRNAs, their specific functions and complex molecular mechanisms driving the onset and progression of cervical cancer. Increasing evidence suggests that circRNAs can serve as invaluable biomarkers for early detection of cervical cancer and promising therapeutic targets for intervention. Delving into the complex interaction between circRNAs and cervical cancer paves the way for innovative and personalized approaches to combat this serious disease, aiming at reducing its impact on women’s health worldwide and improve patient outcomes. Unraveling the mysteries of circRNAs in the context of cervical cancer makes the prospects for a breakthrough in its diagnosis and treatment more promising.
About the Authors
S. A. BegliarzadeRussian Federation
Sema A. Begliarzade — Postgraduate Student, Department of Oncology, Radiology and Radiotheraph
Tyumen
R. I. Tamrazov
Russian Federation
Rasim I. Tamrazov — Dr. Sci. (Med.), Prof., Department of Oncology, Radiology and Radiotheraphy
Tyumen
References
1. Pimple S.A., Mishra G.A. Global strategies for cervical cancer prevention and screening. Minerva Ginecol. 2019;71(4):313–20. DOI: 10.23736/S0026-4784.19.04397-1
2. Perkins R.B., Wentzensen N., Guido R.S., Schiffman M. Cervical cancer screening: a review. JAMA. 2023;330(6):547–58. DOI: 10.1001/jama.2023.13174
3. Aballéa S., Beck E., Cheng X., Demarteau N., Li X., Ma F., et al. Risk factors for cervical cancer in women in China: A metamodel. Womens Health (Lond). 2020;16:1745506520940875. DOI: 10.1177/1745506520940875
4. Kumar L., Harish P., Malik P.S., Khurana S. Chemotherapy and targeted therapy in the management of cervical cancer. Curr Probl Cancer. 2018;42(2):120–8. DOI: 10.1016/j.currproblcancer.2018.01.016
5. Kumar L, Upadhyay A, Jayaraj AS. Chemotherapy and immune check point inhibitors in the management of cervical cancer. Curr Probl Cancer. 2022 Dec;46(6):100900. doi: 10.1016/j.currproblcancer.2022.100900.
6. Buskwofie A., David-West G., Clare C.A. A review of cervical cancer: incidence and disparities. J Natl Med Assoc. 2020;12(2):229–32. DOI: 10.1016/j.jnma.2020.03.002
7. Toden S., Zumwalt T.J., Goel A. Non-coding RNAs and potential therapeutic targeting in cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(1):188491. DOI: 10.1016/j.bbcan.2020.188491
8. Gareev I., Gileva Y., Dzidzaria A., Beylerli O., Pavlov V., Agaverdiev M., et al. Long non-coding RNAs in oncourology. Noncoding RNA Res. 2021;6(3):139–45. DOI: 10.1016/j.ncrna.2021.08.001
9. Li B., Li Y., Hu L., Liu Y., Zhou Q., Wang M., et al. Role of circular RNAs in the pathogenesis of cardiovascular disease. J Cardiovasc Transl Res. 2020;13(4):572–83. DOI: 10.1007/s12265-019-09912-2
10. Li Y., Gao X., Yang C., Yan H., Li C. CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR-1294/ICMT axis. J Clin Lab Anal. 2022;36(5):e24348. DOI: 10.1002/jcla.24348
11. Ma H.B., Yao Y.N., Yu J.J., Chen X.X., Li H.F. Extensive profiling of circular RNAs and the potential regulatory role of circRNA-000284 in cell proliferation and invasion of cervical cancer via sponging miR-506. Am J Transl Res. 2018;10(2):592–604. PMID: 29511454
12. Zhou W.Y., Cai Z.R., Liu J., Wang D.S., Ju H.Q., Xu R.H. Circular RNA: metabolism, functions and interactions with proteins. Mol Cancer. 2020;19(1):172. DOI: 10.1186/s12943-020-01286-3
13. Liang D., Wilusz J.E. Short intronic repeat sequences facilitate circular RNA production. Genes Dev. 2014;28(20):2233–47. DOI: 10.1101/gad.251926.114
14. Chen C.K., Cheng R., Demeter J., Chen J., Weingarten-Gabbay S., Jiang L., et al. Structured elements drive extensive circular RNA translation. Mol Cell. 2021;81(20):4300–18.e13. DOI: 10.1016/j.molcel.2021.07.042
15. Misir S., Wu N., Yang B.B. Specific expression and functions of circular RNAs. Cell Death Differ. 2022;29(3):481–91. DOI: 10.1038/s41418-022-00948-7
16. Kristensen L.S., Andersen M.S., Stagsted L.V.W., Ebbesen K.K., Hansen T.B., Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20(11):675–91. DOI: 10.1038/s41576-019-0158-7
17. Kristensen L.S., Jakobsen T., Hager H., Kjems J. The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol. 2022;19(3):188–206. DOI: 10.1038/s41571-021-00585-y
18. Li F., Yang Q., He A.T., Yang B.B. Circular RNAs in cancer: Limitations in functional studies and diagnostic potential. Semin Cancer Biol. 2021;75:49–61. DOI: 10.1016/j.semcancer.2020.10.002
19. Beilerli A., Gareev I., Beylerli O., Yang G., Pavlov V., Aliev G., et al. Circular RNAs as biomarkers and therapeutic targets in cancer. Semin Cancer Biol. 2022;83:242–52. DOI: 10.1016/j.semcancer.2020.12.026
20. Zang J., Lu D., Xu A. The interaction of circRNAs and RNA binding proteins: An important part of circRNA maintenance and function. J Neurosci Res. 2020;98(1):87–97. DOI: 10.1002/jnr.24356
21. Qu S., Yang X., Li X., Wang J., Gao Y., Shang R., et al. Circular RNA: A new star of noncoding RNAs. Cancer Lett. 2015;365(2):141–8. DOI: 10.1016/j.canlet.2015.06.003
22. Rogalska M.E., Vivori C., Valcárcel J. Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects. Nat Rev Genet. 2023;24(4):251–69. DOI: 10.1038/s41576-022-00556-8
23. Zheng S., Gu T., Bao X., Sun J., Zhao J., Zhang T., et al. Circular RNA hsa_circ_0014243 may serve as a diagnostic biomarker for essential hypertension. Exp Ther Med. 2019;17(3):1728–36. DOI: 10.3892/etm.2018.7107
24. Ye Y.L., Yin J., Hu T., Zhang L.P., Wu L.Y., Pang Z. Increased circulating circular RNA_103516 is a novel biomarker for inflammatory bowel disease in adult patients. World J Gastroenterol. 2019;25(41):6273–88. DOI: 10.3748/wjg.v25.i41.6273
25. Lei M., Zheng G., Ning Q., Zheng J., Dong D. Translation and functional roles of circular RNAs in human cancer. Mol Cancer. 2020;19(1):30. DOI: 10.1186/s12943-020-1135-7
26. Chen L., Shan G. CircRNA in cancer: Fundamental mechanism and clinical potential. Cancer Lett. 2021;505:49–57. DOI: 10.1016/j.canlet.2021.02.004
27. Fasolo F., Di Gregoli K., Maegdefessel L., Johnson J.L. Non-coding RNAs in cardiovascular cell biology and atherosclerosis. Cardiovasc Res. 2019;115(12):1732–56. DOI: 10.1093/cvr/cvz203
28. Beilerli A., Begliarzade S., Sufianov A., Ilyasova T., Liang Y., Beylerli O. Circulating ciRS-7 as a potential non-invasive biomarker for epithelial ovarian cancer: An investigative study. Noncoding RNA Res. 2022;7(3):197–204. DOI: 10.1016/j.ncrna.2022.07.004
29. Hao Z., Yang J., Wang C., Li Y., Zhang Y., Dong X., et al. MicroRNA-7 inhibits metastasis and invasion through targeting focal adhesion kinase in cervical cancer. Int J Clin Exp Med. 2015;8(1):480–7. PMID: 25785020
30. Zhou X., Chen J., Tang W. The molecular mechanism of HOTAIR in tumorigenesis, metastasis, and drug resistance. Acta Biochim Biophys Sin (Shanghai). 2014;46(12):1011–5. DOI: 10.1093/abbs/gmu104
31. Suto T., Yokobori T., Yajima R., Morita H., Fujii T., Yamaguchi S., et al. MicroRNA-7 expression in colorectal cancer is associated with poor prognosis and regulates cetuximab sensitivity via EGFR regulation. Carcinogenesis. 2015;36(3):338–45. DOI: 10.1093/carcin/bgu242
32. Li Y., Zheng F., Xiao X., Xie F., Tao D., Huang C., et al. CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells. EMBO Rep. 2022;23(11):e56102. DOI: 10.15252/embr.202256102
33. Xiao-Long M., Kun-Peng Z., Chun-Lin Z. Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma. J Cancer. 2018;9(10):1856–62. DOI: 10.7150/jca.24619
34. Chen X., Mao R., Su W., Yang X., Geng Q., Guo C., et al. Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer. Autophagy. 2020;16(4):659–71. DOI: 10.1080/15548627.2019.1634945
35. Wen J., Liao J., Liang J., Chen X.P., Zhang B., Chu L. Circular RNA HIPK3: A Key Circular RNA in a Variety of Human Cancers. Front Oncol. 2020;10:773. DOI: 10.3389/fonc.2020.00773
36. Shen Z., Zhou L., Zhang C., Xu J. Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel. Cancer Lett. 2020;468:88–101. DOI: 10.1016/j.canlet.2019.10.006
37. Yang T., Li Y., Zhao F., Zhou L., Jia R. Circular RNA Foxo3: a promising cancer-associated biomarker. Front Genet. 2021;12:652995. DOI: 10.3389/fgene.2021.652995
38. Yu T., Wang Y., Fan Y., Fang N., Wang T., Xu T., et al. CircRNAs in cancer metabolism: a review. J Hematol Oncol. 2019;12(1):90. DOI: 10.1186/s13045-019-0776-8
39. Wang J., Zhu S., Meng N., He Y., Lu R., Yan G.R. ncRNA-Encoded peptides or proteins and cancer. Mol Ther. 2019;27(10):1718–25. DOI: 10.1016/j.ymthe.2019.09.001
40. Bose R., Ain R. Regulation of transcription by circular RNAs. Adv Exp Med Biol. 2018;1087:81–94. DOI: 10.1007/978-981-13-1426-1_7
41. Li L., Li W., Chen N., Zhao H., Xu G., Zhao Y., et al. FLI1 exonic circular RNAs as a novel oncogenic driver to promote tumor metastasis in small cell lung cancer. Clin Cancer Res. 2019;25(4):1302–17. DOI: 10.1158/1078-0432.CCR-18-1447
42. Wilson J.E., Pestova T.V., Hellen C.U., Sarnow P. Initiation of protein synthesis from the A site of the ribosome. Cell. 2000;102(4):511–20. DOI: 10.1016/s0092-8674(00)00055-6
43. Greco S., Cardinali B., Falcone G., Martelli F. Circular RNAs in muscle function and disease. Int J Mol Sci. 2018;19(11):3454. DOI: 10.3390/ijms19113454
44. Zhang M., Huang N., Yang X., Luo J., Yan S., Xiao F., et al. A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene. 2018;37(13):1805–14. DOI: 10.1038/s41388-017-0019-9
45. Begum S., Yiu A., Stebbing J., Castellano L. Novel tumour suppressive protein encoded by circular RNA, circ-SHPRH, in glioblastomas. Oncogene. 2018;37(30):4055–57. DOI: 10.1038/s41388-018-0230-3
46. 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. DOI: 10.3322/caac.21660
47. Arbyn M., Ronco G., Anttila A., Meijer C.J., Poljak M., Ogilvie G., et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012;30 Suppl 5:F88–99. DOI: 10.1016/j.vaccine.2012.06.095
48. Ergünay K., Misirlioğlu M., Firat P., Tuncer Z.S., Tuncer S., Yildiz I., et al. Detection and typing of human papilloma virus by polymerase chain reaction and hybridization assay in cervical samples with cytological abnormalities. Mikrobiyol Bul. 2008;42(2):273–82.
49. Fontham E.T.H., Wolf A.M.D., Church T.R., Etzioni R., Flowers C.R., et al. Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society. CA Cancer J Clin. 2020;70(5):321–46. DOI: 10.3322/caac.21628
50. Bhattacharjee R., Das S.S., Biswal S.S., Nath A., Das D., Basu A., et al. Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies. Crit Rev Oncol Hematol. 2022;174:103675. DOI: 10.1016/j.critrevonc.2022.103675
51. Li Z., Ruan Y., Zhang H., Shen Y., Li T., Xiao B. Tumor-suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets. Cancer Sci. 2019;110(12):3630–8. DOI: 10.1111/cas.14211
52. Xue C., Wei J., Li M., Chen S., Zheng L., Zhan Y., et al. The emerging roles and clinical potential of circSMARCA5 in cancer. Cells. 2022;11(19):3074. DOI: 10.3390/cells11193074
53. Zhang J., Zhao X., Zhang J., Zheng X., Li F. Circular RNA hsa_circ_0023404 exerts an oncogenic role in cervical cancer through regulating miR-136/TFCP2/YAP pathway. Biochem Biophys Res Commun. 2018;501(2):428–33. DOI: 10.1016/j.bbrc.2018.05.006
54. Yang W., Xie T. Hsa_circ_CSPP1/MiR-361-5p/ITGB1 regulates proliferation and migration of cervical cancer (CC) by modulating the PI3K-Akt signaling pathway. Reprod Sci. 2020;27(1):132–44. DOI: 10.1007/s43032-019-00008-5
55. 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. DOI: 10.3389/fonc.2020.00150
56. Li M., Ren C.X., Zhang J.M., Xin X.Y., Hua T., Wang H.B., et al. The effects of miR-195-5p/MMP14 on proliferation and invasion of cervical carcinoma cells through TNF signaling pathway based on bioinformatics analysis of microarray profiling. Cell Physiol Biochem. 2018;50(4):1398–413. DOI: 10.1159/000494602
57. Xu Y.J., Yu H., Liu G.X. Hsa_circ_0031288/hsa-miR-139-3p/Bcl-6 regulatory feedback circuit influences the invasion and migration of cervical cancer HeLa cells. J Cell Biochem. 2020;121(10):4251–60. DOI: 10.1002/jcb.29650
58. Ma H., Tian T., Liu X., Xia M., Chen C., Mai L., et al. Upregulated circ_0005576 facilitates cervical cancer progression via the miR-153/KIF20A axis. Biomed Pharmacother. 2019;118:109311. DOI: 10.1016/j.biopha.2019.109311
59. Al-Hawary S.I.S., Asghar W., Amin A., Mustafa Y.F., Hjazi A., Almulla A.F., et al. Circ_0067934 as a novel therapeutic target in cancer: From mechanistic to clinical perspectives. Pathol Res Pract. 2023;245:154469. DOI: 10.1016/j.prp.2023.154469
60. Lin E., Liu S., Xiang W., Zhang H., Xie C. CircEIF4G2 Promotes Tumorigenesis and Progression of Osteosarcoma by Sponging miR-218. Biomed Res Int. 2020;2020:8386936. DOI: 10.1155/2020/8386936
61. Gandhi N.S., Tekade R.K., Chougule M.B. Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: current progress and advances. J Control Release. 2014;194:238–56. DOI: 10.1016/j.jconrel.2014.09.001
62. Sadreddini S., Safaralizadeh R., Baradaran B., Aghebati-Maleki L., Hosseinpour-Feizi M.A., Shanehbandi D., et al. Chitosan nanoparticles as a dual drug/siRNA delivery system for treatment of colorectal cancer. Immunol Lett. 2017;181:79–86. DOI: 10.1016/j.imlet.2016.11.013
63. Yang Y.C., Cai J., Yin J., Zhang J., Wang K.L., Zhang Z.T. Heparin-functionalized Pluronic nanoparticles to enhance the antitumor efficacy of sorafenib in gastric cancers. Carbohydr Polym. 2016;136:782–90. DOI: 10.1016/j.carbpol.2015.09.023
64. Luo C.L., Liu Y.Q., Wang P., Song C.H., Wang K.J., Dai L.P., et al. The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. Biomed Pharmacother. 2016;82:595–605. DOI: 10.1016/j.biopha.2016.05.029
65. Men K., Duan X., He Z., Yang Y., Yao S., Wei Y. CRISPR/Cas9- mediated correction of human genetic disease. Sci China Life Sci. 2017;60(5):447–57. DOI: 10.1007/s11427-017-9032-4
66. Gampa S.C., Garimella S.V., Pandrangi S. Nano-TRAIL: a promising path to cancer therapy. Cancer Drug Resist. 2023;6(1):78–102. DOI: 10.20517/cdr.2022.82
67. Sufianov A., Begliarzade S., Beilerli A., Liang Y., Ilyasova T., Beylerli O. Circular RNAs as biomarkers for lung cancer. Noncoding RNA Res. 2022;8(1):83–8. DOI: 10.1016/j.ncrna.2022.11.002
68. Yao S., Yin Y., Jin G., Li D., Li M., Hu Y., et al. Exosome-mediated delivery of miR-204-5p inhibits tumor growth and chemoresistance. Cancer Med. 2020;9(16):5989–98. DOI: 10.1002/cam4.3248
69. Begliarzade S., Beilerli A., Sufianov A., Tamrazov R., Kudriashov V., Ilyasova T., et al. Long non-coding RNAs as promising biomarkers and therapeutic targets in cervical cancer. Noncoding RNA Res. 2023;8(2):233–9. DOI: 10.1016/j.ncrna.2023.02.006
70. Li Y., Gao X., Huang Y., Zhu X., Chen Y., Xue L., et al. Tumor microenvironment promotes lymphatic metastasis of cervical cancer: its mechanisms and clinical implications. Front Oncol. 2023;13:1114042. DOI: 10.3389/fonc.2023.1114042
71. Sufianov A., Begliarzade S., Kudriashov V., Beilerli A., Ilyasova T., Liang Y., et al. The role of circular RNAs in the pathophysiology of oral squamous cell carcinoma. Noncoding RNA Res. 2022;8(1):109–14. DOI: 10.1016/j.ncrna.2022.11.004
72. Preußer C., Hung L.H., Schneider T., Schreiner S., Hardt M., Moebus A., et al. Selective release of circRNAs in platelet-derived extracellular vesicles. J Extracell Vesicles. 2018;7(1):1424473. DOI: 10.1080/20013078.2018
73. Guo X., Gao C., Yang D.H., Li S. Exosomal circular RNAs: A chief culprit in cancer chemotherapy resistance. Drug Resist Updat. 2023;67:100937. DOI: 10.1016/j.drup.2023.100937
Review
For citations:
Begliarzade S.A., Tamrazov R.I. Circular RNAs in Cervical Cancer: What are the Prospects? Creative surgery and oncology. 2023;13(4):320-329. (In Russ.) https://doi.org/10.24060/2076-3093-2023-13-4-320-329