The expression profile of exosomal miRNAs in cervical cancer cells (HeLa) compared to normal cells and evaluating the key genes related to them

Document Type : Original Article

Authors

1 M.Sc. of Cellular and Molecular Biology, Department of Genetics, School of Basic Sciences, Shahrekord University, Shahrekord, Iran.

2 Assistant Professor, Department of Computer Science, School of Mathematical Sciences, Shahrekord University, Shahrekord, Iran.

3 Associate Professor, Department of Genetics, School of Basic Sciences, Shahrekord University, Shahrekord, Iran.

Abstract

Introduction: Cervical cancer is the fourth most common cancer among women worldwide and is a heterogeneous disease. The exosomal miRNAs could be applied as diagnostic biomarkers and therapeutic targets in cervical cancer. The present study was performed with aim to use a bioinformatics analysis to identify key miRNAs and related genes and pathways in exosomes derived from cervical cancer cells.
Methods: In this study, the differential expression of exosomal miRNA and RNAs in healthy and HeLa cells was investigated by analyzing the GEO database for miR-seq and RNA-seq in R software. Subsequently, overlapped miRNA target genes and differentially mRNA from exosome were selected and then, GO and KEGG pathway analysis was performed. The overlapped genes were integrated to construct a PPI network and hub genes selection.
Results: In the present study, it was observed that 31 miRNAs were upregulated and 16 miRNAs were downregulated in exosomes. Also, 341 overlapped genes from miRNAs targets and mRNA-seq were selected for future analysis. GO analysis indicated that overlapped genes were significantly enriched in the leucine transport, MAP kinase phosphatase activity, and glutamine transport. KEGG analysis suggested that the genes were enriched in cellular senescence, p53 signaling pathway and cell cycle. The top ten genes including CCNB1, BUB1, KIF20A, MKI67, FOXM1, BIRC5, NCAPH, ZWINT, GINS2, and ASF1B were identified from the PPI network.
Conclusion: The results identified key miRNAs with altered expression and characterizing key genes in exosomes derived cervical cancer cells. This study will provide novel insights to determine the potential mechanisms associated exosomes derived from cancer cells in cervical cancer progression.

Keywords

References

  1.  

    1. D’Oria O, Corrado G, Laganà AS, Chiantera V, Vizza E, Giannini A. New advances in cervical cancer: from bench to bedside. International Journal of Environmental Research and Public Health 2022; 19(12):7094.
    2. Kashyap N, Krishnan N, Kaur S, Ghai S. Risk factors of cervical cancer: a case-control study. Asia-Pacific journal of oncology nursing 2019; 6(3):308-14.
    3. Wang J, Wang T, Yang YY, Chai YL, Shi F, Liu ZI. Patient age, tumor appearance and tumor size are risk factors for early recurrence of cervical cancer. Molecular and clinical oncology 2015; 3(2):363-6.
    4. Achen MG, McColl BK, Stacker SA. Focus on lymphangiogenesis in tumor metastasis. Cancer cell 2005; 7(2):121-7.
    5. Nahand JS, Taghizadeh‐boroujeni S, Karimzadeh M, Borran S, Pourhanifeh MH, Moghoofei M, et al. microRNAs: new prognostic, diagnostic, and therapeutic biomarkers in cervical cancer. Journal of cellular physiology 2019; 234(10):17064-99.
    6. Ambros V. The functions of animal microRNAs. Nature 2004; 431(7006):350-5.
    7. Vishnoi A, Rani S. MiRNA biogenesis and regulation of diseases: an overview. MicroRNA profiling: Methods and protocols 2017: 1-10.
    8. Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Molecular cancer 2016; 15(1):1-10.
    9. Mathivanan S, Simpson RJ. ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 2009; 9(21):4997-5000.
    10. Lässer C, Seyed Alikhani V, Ekström K, Eldh M, Torregrosa Paredes P, Bossios A, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. Journal of translational medicine 2011; 9(1):1-8.
    11. Weber JA, Baxter DH, Zhang S, Huang DY, How Huang K, Jen Lee M, et al. The microRNA spectrum in 12 body fluids. Clinical chemistry 2010; 56(11):1733-41.
    12. Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. The Lancet 2002; 360(9329):295-305.
    13. Zhang J, Li S, Li L, Li M, Guo C, Yao J, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics, proteomics & bioinformatics 2015; 13(1):17-24.
    14. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecologic oncology 2008; 110(1):13-21.
    15. Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Frontiers in genetics 2019; 10:478.
    16. Zhang H, Liang Y, Han S, Peng C, Li Y. Long noncoding RNA and protein interactions: from experimental results to computational models based on network methods. International journal of molecular sciences 2019; 20(6):1284.
    17. Jiang L, Hong L, Yang W, Zhao Y, Tan A, Li Y. Co-expression network analysis of the lncRNAs and mRNAs associated with cervical cancer progression. Archives of Medical Science 2019; 15(3):754-64.
    18. Mijit M, Caracciolo V, Melillo A, Amicarelli F, Giordano A. Role of p53 in the Regulation of Cellular Senescence. Biomolecules 2020; 10(3):420.
    19. Saretzki G. Cellular senescence in the development and treatment of cancer. Current pharmaceutical design 2010; 16(1):79-100.
    20. Wang T, Wu X, Song Y, Cheng H. Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells. Journal of Cancer 2020; 11(22):6704.
    21. Jiramongkol Y, Lam EW. FOXO transcription factor family in cancer and metastasis. Cancer and Metastasis Reviews 2020; 39:681-709.
    22. Ramezani A, Nikravesh H, Faghihloo E. The roles of FOX proteins in virus‐associated cancers. Journal of Cellular Physiology 2019; 234(4):3347-61.
    23. Bai X, Wang W, Zhao P, Wen J, Guo X, Shen T, et al. LncRNA CRNDE acts as an oncogene in cervical cancer through sponging miR-183 to regulate CCNB1 expression. Carcinogenesis 2020; 41(1):111-21.
    24. Niméus‐Malmström E, Koliadi A, Ahlin C, Holmqvist M, Holmberg L, Amini RM, et al. Cyclin B1 is a prognostic proliferation marker with a high reproducibility in a population‐based lymph node negative breast cancer cohort. International journal of cancer 2010; 127(4):961-7.
    25. Morgan EL, Wasson CW, Hanson L, Kealy D, Pentland I, McGuire V, et al. STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle. PLoS pathogens 2018; 14(4):e1006975.
    26. Nandi D, Cheema PS, Jaiswal N, Nag A. FoxM1: repurposing an oncogene as a biomarker. InSeminars in Cancer Biology 2018; 52:74-84.
    27. Katoh M, Igarashi M, Fukuda H, Nakagama H, Katoh M. Cancer genetics and genomics of human FOX family genes. Cancer letters 2013; 328(2):198-206.
    28. Fäldt Beding A, Larsson P, Helou K, Einbeigi Z, Parris TZ. Pan-cancer analysis identifies BIRC5 as a prognostic biomarker. BMC cancer 2022; 22(1):1-13.
    29. Xia L, Su X, Shen J, Meng Q, Yan J, Zhang C, et al. ANLN functions as a key candidate gene in cervical cancer as determined by integrated bioinformatic analysis. Cancer management and research 2018: 663-70.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 26, Issue 8
October 2023
Pages 55-68

Files

Share

How to cite

Statistics