The dysregulation of microarray gene expression in cervical cancer is associated with overexpression of a unique messenger RNA signature
-
Seyedeh Zahra Mousavi
,
Vahdat Poortahmasebi
,
Talat Mokhtari-Azad
,
Shohreh Shahmahmoodi
,
Mohammad Farahmand
,
Mahdieh Farzanehpour
,
Somayeh Jalilvand
Abstract
Background and Objectives: Human papillomavirus (HPV) is the fourth most common cause of cervical cancer (CC). The aim of the present study was to investigate gene expression levels of previously identified transcriptional signatures for malignant and non-malignant CC.
Materials and Methods: To validate of previously analyzed microarray gene expression data, we selected two hub genes (CDK1 and PLK1) and four differentially expressed mRNAs that were common in pre-malignant-normal and malignant-pre-malignant networks (SMS, NNT, UHMK1 and DEPDC1). To this purpose, the study included women diagnosed histologically with malignant CC (n=15), pre-malignant (n=15), and normal subjects (n=15). The expression of six host genes and viral E6/E7 genes were measured by quantitative Real-Time PCR.
Results: The results showed higher expression of CDK1/PLK1 hub genes and SMS, NNT and UHMK1 genes in malignant CC group than non-malignant CC group and normal group. A positive correlation was observed between gene expression of viral E6/E7 oncogenes and UHMK1 gene.
Conclusion: Dysregulation of several mRNA signatures are a common feature of CC and can be potentially used as diagnostic and prognostic biomarkers as well as can be applied to therapeutic targets for CC treatment.
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24. Ho H-Y, Lin Y-T, Lin G, Wu P-R, Cheng M-L. Nicotinamide nucleotide transhydrogenase (NNT) deficiency dysregulates mitochondrial retrograde signaling and impedes proliferation. Redox Biol 2017; 12: 916-928.
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29. Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch FX. Viral RNA Patterns and High Viral Load Reliably Define Oropharynx Carcinomas with Active HPV16 Involvement. Cancer Res 2012; 72:4993-5003.
30. Cerasuolo A, Annunziata C, Tortora M, Starita N, Stellato G, Greggi S, et al. Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma. Oncotarget 2017; 8:34070-34081.
31. Woodman CBJ, Collins SI, Young LS. The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer 2007; 7: 11-22.
2. Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 1999; 83: 18-29.
3. Zur Hausen H. Papillomavirus infections--a major cause of human cancers. Biochim Biophys Acta 1996; 1288: F55-78.
4. Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association. Rev Med Virol 2015; 25 Suppl 1(Suppl Suppl 1):2-23.
5. Ghittoni R, Accardi R, Chiocca S, Tommasino M. Role of human papillomaviruses in carcinogenesis.
Ecancermedicalscience 2015; 9: 526.
6. Senapati R, Senapati NN, Dwibedi B. Molecular mechanisms of HPV mediated neoplastic progression. Infect Agent Cancer 2016; 11: 59.
7. Mousavi SZ, Poortahmasebi V, Mokhtari-Azad T, Shahmahmoodi S, Jalilvand S, Rafiei Alavi E. CDK1 and PLK1 are key regulator proteins in human Papilloma virus Type 16-Positive Cervical Cancer: A Network-Based Study. Med Sci 2020; 24: 201-214.
8. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-408.
9. Chakraborty D, Maulik U. Identifying cancer biomarkers from microarray data using feature selection and semisupervised learning. IEEE J Transl Eng Health Med 2014; 2: 4300211.
10. Clough E, Barrett T. The gene expression omnibus database. Methods Mol Biol 2016; 1418:93-110.
11. Malumbres M. Cyclin-dependent kinases. Genome Biol 2014; 15: 122.
12. Enserink JM, Kolodner RD. An overview of Cdk1-controlled targets and processes. Cell Div 2010; 5: 11.
13. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009; 9: 153-166.
14. Hochegger H, Takeda S, Hunt T. Cyclin-dependent kinases and cell-cycle transitions: does one fit all? Nat Rev Mol Cell Biol 2008; 9: 910-916.
15. Fan X, Chen JJ. Role of Cdk1 in DNA damage-induced G1 checkpoint abrogation by the human papillomavirus E7 oncogene. Cell Cycle 2014; 13: 3249-3259.
16. Luo Y, Wu Y, Peng Y, Liu X, Bie J, Li S. Systematic analysis to identify a key role of CDK1 in mediating gene interaction networks in cervical cancer development. Ir J Med Sci 2016; 185: 231-239.
17. Scotto L, Narayan G, Nandula SV, Arias-Pulido H, Subramaniyam S, Schneider A, et al. Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes Chromosomes Cancer 2008; 47: 755-765.
18. Colicino EG, Hehnly H. Regulating a key mitotic regulator, polo-like kinase 1 (PLK1). Cytoskeleton (Hoboken) 2018; 75: 481-494.
19. Weiss L, Efferth T. Polo-like kinase 1 as target for cancer therapy. Exp Hematol Oncol 2012; 1: 38.
20. Stone A, Sutherland RL, Musgrove EA. Inhibitors of cell cycle kinases: recent advances and future prospects as cancer therapeutics. Crit Rev Oncog 2012; 17: 175-198.
21. Allen WL, McLean EG, Boyer J, McCulla A, Wilson PM, Coyle V, et al. The role of spermidine/spermine N1-acetyltransferase in determining response to chemotherapeutic agents in colorectal cancer cells. Mol Cancer Ther 2007; 6: 128-137.
22. Chen Y, Zhuang H, Chen X, Shi Z, Wang X. Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer. Oncol Rep 2018; 39: 2845-2854.
23. Duan Z, Song Y, Zou X, Liu S, Zhang W, Liu L. Nicotinamide nucleotide transhydrogenase acts as a new prognosis biomarker in hepatocellular carcinoma. Int J Clin Exp Pathol 2020; 13: 972-978.
24. Ho H-Y, Lin Y-T, Lin G, Wu P-R, Cheng M-L. Nicotinamide nucleotide transhydrogenase (NNT) deficiency dysregulates mitochondrial retrograde signaling and impedes proliferation. Redox Biol 2017; 12: 916-928.
25. Spielman RS, Bastone LA, Burdick JT, Morley M, Ewens WJ, Cheung VG. Common genetic variants account for differences in gene expression among ethnic groups. Nat Genet 2007; 39: 226-231.
26. Manceau V, Kremmer E, Nabel EG, Maucuer A. The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice. PLoS One 2012; 7(8):e43946.
27. Boehm M, Yoshimoto T, Crook MF, Nallamshetty S, True A, Nabel GJ, et al. A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. EMBO J 2002; 21: 3390-3401.
28. Höfler D, Böhmer G, von Wasielewski R, Neumann H, Halec G, Holzinger D, et al. HPV16 RNA patterns defined by novel high-throughput RT-qPCR as triage marker in HPV-based cervical cancer precursor screening. Gynecol Oncol 2015; 138: 676-682.
29. Holzinger D, Schmitt M, Dyckhoff G, Benner A, Pawlita M, Bosch FX. Viral RNA Patterns and High Viral Load Reliably Define Oropharynx Carcinomas with Active HPV16 Involvement. Cancer Res 2012; 72:4993-5003.
30. Cerasuolo A, Annunziata C, Tortora M, Starita N, Stellato G, Greggi S, et al. Comparative analysis of HPV16 gene expression profiles in cervical and in oropharyngeal squamous cell carcinoma. Oncotarget 2017; 8:34070-34081.
31. Woodman CBJ, Collins SI, Young LS. The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer 2007; 7: 11-22.
| Files | ||
| Issue | Vol 12 No 6 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v12i6.5039 | |
| Keywords | ||
| Human papillomavirus; Cervical cancer; Microarray; Gene expression | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mousavi SZ, Poortahmasebi V, Mokhtari-Azad T, Shahmahmoodi S, Farahmand M, Farzanehpour M, Jalilvand S. The dysregulation of microarray gene expression in cervical cancer is associated with overexpression of a unique messenger RNA signature. Iran J Microbiol. 2020;12(6):629-635.
