Nur Deniz Dibek¹*, Esra Guzel Tanoglu²*, Elif Sibel Aslan³**, Sajjad Eslemkhah⁴, Rabia Erdoğdu⁵, Mustafa Ozen^6,7

¹Biruni University, Institute of Health Sciences, Department of Molecular and Medical Genetics, Turkey
²University of Health Sciences Turkey, Institute of Hamidiye Health Sciences, Department of Molecular Biology and Genetics, Turkey
^3,4,5Biruni University, Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Turkey
⁶Baylor College of Medicine, Department of Pathology and Immunology,Houston,TX,USA. HYPERLINK "mozen@bcm.edu" mozen@bcm.edu
⁷Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkiye. mustafa.ozen@iuc.edu.tr

**Corresponding Author: Elif Sibel Aslan, Biruni University, Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Turkey.

Received: August 19, 2024; Published: September 11, 2024

Abstract

Laryngeal cancer (LCa) is the most common and aggressive type of head and neck region cancers. The molecular understanding of Laryngeal cancer has been gaining of interest in recent years. Timely diagnosis is crucial for effective treatment and positive prognosis. The early diagnosis may increase the treatment success at the molecular level. Existing evidence on the association of microRNAs (miRNAs) has provided the chance to further analyze the possibilities of the miRNAs to be applied in early diagnosis and further therapies. Our study aims to show functional analysis of miR-26b, miR-200c-3p, miR-203, miR-363-3p, and miR-1825, which were already identified in our previous microarray studies that could be associated with squamous cell laryngeal cancer. In this study, human epithelial type 2 (Hep-2) cell lines, which are from human laryngeal carcinoma, were transfected with the targeted miRNAs and were throughly observed and analyzed for the alteration in cell proliferation, migration, and invasion using soft agar assays. The result of the experiments detected an inverse association between the decline in miR-203 and miR363-3p and rapid proliferation of Hep-2 cells. The findings indicated that miR-203 and miR-363-3p act as tumor suppressor and slow down proliferation, migration, invasion, and tumorigenesis. Based on the findings on this study, these miRNAs could be considered as promising candidates for being diagnostic biomarkers in laryngeal cancer.

 Keywords: Laryngeal Cancer; miR-203; miR363-3p; Hep-2

References

1. Sung H., et al. “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries”. CA: A Cancer Journal for Clinicians3 (2021): 209-249.
2. Mody MD., et al. “Head and neck cancer”. The Lancet10318 (2021): 2289-2299.
3. Son E., et al. “Cancers of the major salivary gland”. Journal of Oncology Practice2 (2018): 99-108.
4. Sessions D G. Surgical pathology of cancer of the larynx and hypopharynx”. The Laryngoscope6 (1976): 814-839.
5. Gourin CG., et al. “The effect of treatment on survival in patients with advanced laryngeal carcinoma”. The Laryngoscope7 (2009): 1312-1317.
6. Bosetti C., et al. “ Effects of smoking cessation on the risk of laryngeal cancer: An overview of published studies”. Oral Oncology9 (2006): 866-872.
7. Spitz MR. “Epidemiology and risk factors for head and neck cancer”. Seminars in Oncology (1994).
8. Siegel R L., et al. “Cancer statistics, 2015”. CA: A Cancer Journal for Clinicians1 (2015): 5-29.
9. Elicin O and Giger R. “Comparison of current surgical and non-surgical treatment strategies for early and locally advanced stage glottic laryngeal cancer and their outcome”. Cancers 12.3 (2020): 1-20.
10. Forastiere A., et al. “Use of larynx-preservation strategies in the treatment of laryngeal cancer: American Society of Clinical Oncology clinical practice guideline update”. Journal of Clinical Oncology11 (2018): 1143-1169.
11. Pelletier C and Weidhaas JB. “MicroRNA binding site polymorphisms as biomarkers of cancer risk”. Expert Review of Molecular Diagnostics6 (2010): 817-829.
12. Yu X and Li Z. “MicroRNAs regulate vascular smooth muscle cell functions in atherosclerosis (Review)”. International Journal of Molecular Medicine 4 (2014): 923-933.
13. Li Z., et al. “MicroRNA dysregulation in rhabdomyosarcoma: A new player enters the game”. Cell Proliferation 5 (2015): 511-516.
14. Humphries B., et al. “The role of microRNAs in metal carcinogen-induced cell malignant transformation and tumorigenesis”. Food and Chemical Toxicology 98 (2016): 58-65.
15. Leoncini E., et al. “Adult height and head and neck cancer: A pooled analysis within the INHANCE Consortium”. Head and Neck10 (2014): 1391.
16. Lu E., et al. “Enhanced miR-9 promotes laryngocarcinoma cell survival via down-regulating PTEN”. Biomed and Pharma 84 (2016): 608-613.
17. Zhang L., et al. “MicroRNA-10b Triggers the Epithelial-Mesenchymal Transition (EMT) of Laryngeal Carcinoma Hep-2 Cells by Directly Targeting the E-cadherin”. Applied Biochemistry and Biotechnology1 (2015): 33-44.
18. Chen Y., et al. “Expression of B-cell translocation gene 2 is associated with favorable prognosis in hepatocellular carcinoma patients and sensitizes irradiation-induced hepatocellular carcinoma cell apoptosis in vitro and in nude mice”. Oncology Letters4 (2017): 2366-2372.
19. Liu M., et al. “ Regulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma”. Cell Research7 (2009): 828-837.
20. Zhong G and Xiong X. “miR-205 promotes proliferation and invasion of laryngeal squamous cell carcinoma by suppressing CDK2AP1 expression”. Biological Research 48 (2015): 1-8.
21. Xiao X., et al. “MicroRNA-93 regulates cyclin G2 expression and plays an oncogenic role in laryngeal squamous cell carcinoma”. International Journal of Oncology1 (2015): 161-174.
22. Shen Z., et al. “MicroRNA-519a demonstrates significant tumour suppressive activity in laryngeal squamous cells by targeting anti-carcinoma HuR gene”. The Journal of Laryngology and Otology 12 (2013): 1194-1202.
23. Tian L., et al. “MiR-203 is downregulated in laryngeal squamous cell carcinoma and can suppress proliferation and induce apoptosis of tumours”. Tumor Biology 35 (2014): 5953-5963.
24. Zhang L., et al. “MicroRNA-34 family: A potential tumor suppressor and therapeutic candidate in cancer”. Journal of Experimental and Clinical Cancer Research 1 (2019): 1-13.
25. Li W., et al. “microRNA-34a/c function as tumor suppressors in Hep-2 laryngeal carcinoma cells and may reduce GALNT7 expression”. Molecular Medicine Reports 4 (2014): 1293-1298.
26. Morgan E., et al. “Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN”. Gut2 (2023): 338-344.
27. Ciolofan M S., et al. “Clinical, Histological and Immunohistochemical Evaluation of Larynx Cancer”. Current Health Sciences Journal 4 (2017): 367-375.
28. Forastiere A A., et al. “ Long-term results of RTOG 91-11: A comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer”. Journal of Clinical Oncology 7 (2013): 845-852.
29. Karatas O F., et al. “ Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens”. BMC Cancer1 (2016): 1-11.
30. Peng Y and Croce C M. “The role of microRNAs in human cancer”. Signal Transduction and Targeted Therapy 1 (2016).
31. Piotrowski I., et al. “miRNAs as Biomarkers for Diagnosing and Predicting Survival of Head and Neck Squamous Cell Carcinoma Patients”. Multidisciplinary Digital Publishing Institute 16 (2021): 3980-3980.
32. Rafiyan M., et al. “Lysophosphatidic Acid Signaling and microRNAs: New Roles in Various Cancers”. Frontiers Media 12 (2022).
33. Cao P., et al. “ Comprehensive expression profiling of microRNAs in laryngeal squamous cell carcinoma”. Wiley5 (2022): 720-728.
34. Luo J., et al. “miR-375 Suppresses IGF1R Expression and Contributes to Inhibition of Cell Progression in Laryngeal Squamous Cell Carcinoma”. Hindawi Publishing Corporation (2014): 1-11.
35. Iorio M V and Croce CM. “MicroRNAs in cancer: small molecules with a huge impact”. Journal of Clinical Oncology34 (2009): 5848-5856.
36. Shi L., et al. “KRAS induces lung tumorigenesis through microRNAs modulation”. Springer Nature2 (2018).
37. Wang S., et al. “Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer”. Medical Oncology3 (2013).
38. Viticchiè G., et al. “MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines”. Cell Cycle 7 (2011): 1121-1131.
39. Qu Y., et al. “MiR-182 and miR-203 induce mesenchymal to epithelial transition and self-sufficiency of growth signals via repressing SNAI2 in prostate cells”. International Journal of Cancer 3 (2013): 544-555.
40. Zhang Z., et al. “Epigenetic Silencing of miR-203 Upregulates SNAI2 and Contributes to the Invasiveness of Malignant Breast Cancer Cells”. Genes and Cancer 8 (2011): 782-791.
41. Sun Q., et al. “Dysregulated miR-363 affects head and neck cancer invasion and metastasis by targeting podoplanin”. International Journal of Biochemistry and Cell Biology3 (2013): 513-520.
42. Jinlang D., et al. “MiR-363-3p suppresses tumor growth and metastasis of colorectal cancer via targeting SphK2”. Biomedicine and Pharmacotherapy 105 (2018): 922-931.
43. Wang N., et al. “miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC”. PLoS ONE8 (2014).

Citation

Citation: Elif Sibel Aslan., et al. “In vitro Characterization of Mir-203 and Mir-363-3p as Potential Biomarkers in Laryngeal Cancer Cells”.Acta Scientific Medical Sciences 8.10 (2024): 34-42.

Copyright

Copyright: © 2024 Elif Sibel Aslan., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.