Evaluation of Changes in miR-7113-3p, miR-6721-5p and MAP2K1 gene expressions in tumor and normal tissues of patients with oral cancer
Abstract
Backgrounds: Squamous cell carcinoma of the oral cavity (OSCC) is one of the most common cancers in the Head and Neck Squamous Cell Cancer (HNSCC) group. The increasing frequency of oral carcinomas and their late-stage appearance is a major worldwide health concern. MicroRNAs (miRNAs) play an important role in cancer growth and progression, as the available relevant data indicate. However, no information is available about the part miR-7113-3p and miR-6721-5p takes in OSCC. In the present study, the expression of MAP2K1, miR-7113-3p, and miR-6721-5p was examined to determine their possible biological role in the advancement of oral squamous cell carcinoma. Methods: Quantitative Real-Time PCR was applied to investigate the mRNA expression of MAP2K1, miR-7113-3p, and miR-6721-5p in fresh frozen OSCC tissues and adjacent normal fresh frozen tissues of 30 patients and then, the relationship between MAP2K1 Expression and clinical parameters was studied. Results: MAP2K1 expression dramatically increased in tumor tissues compared to the normal tissues, while miR7113-3p and miR-6721-5p expression significantly decreased. Furthermore, a statistical correlation of p=0.04 was also observed between increased MAP2K1 expression and Perineural invasion. In addition, the downregulation of miR-7113-3p was positively correlated with overexpression of MAP2K1 (p=0.0218) and a negative correlation was observed between downregulation of miR-6721-5p and overexpression of MAP2K1 (p=0.7771). Conclusion: Based on the findings, miR-7113-3p and miR-6721-5p might be prospective biomarkers for OSCC patients, and can be utilized to detect OSCC at an early stage of its diagnosis. MAP2K1 overexpression is linked to the development of OSCC and Perineural invasion.
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12. Santoro G, Lapucci C, Giannoccaro M, Caporilli S, Rusin M, Seidenari A, et al. Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (< 4%) Cell-Free DNA Fetal Fraction. Diagnostics. 2021;11(11):2108.
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14. Rivera C. Essentials of oral cancer. International journal of clinical and experimental pathology. 2015;8(9):11884.
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24. Jeong S, Kim S-A, Ahn S-G. HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2. International journal of molecular sciences. 2021;23(1):9.
25. Jin Z, Jia B, Tan L, Liu Y. miR‑330‑3p suppresses liver cancer cell migration by targeting MAP2K1. Oncology Letters. 2019;18(1):314-20.
26. You J, Zhang Y, Li Y, Fang N, Liu B, Zu L, et al. MiR-449a suppresses cell invasion by inhibiting MAP2K1 in non-small cell lung cancer. American journal of cancer research. 2015;5(9):2730.
27. Jain AP, Patel K, Pinto S, Radhakrishnan A, Nanjappa V, Kumar M, et al. MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma. Scientific reports. 2019;9(1):1-12.
28. Lien M-Y, Chang A-C, Tsai H-C, Tsai M-H, Hua C-H, Cheng S-P, et al. Monocyte chemoattractant protein 1 promotes VEGF-A expression in OSCC by activating ILK and MEK1/2 signaling and downregulating miR-29c. Frontiers in Oncology. 2020;10:592415.
29. Judd NP, Winkler AE, Murillo-Sauca O, Brotman JJ, Law JH, Lewis JS, et al. ERK1/2 Regulation of CD44 Modulates Oral Cancer AggressivenessERK1/2 Controls Mouse Oral Cancer Growth via CD44. Cancer research. 2012;72(1):365-74.
30. Lin C, Tu C, Ma Y, Ye P, Shao X, Yang Z, et al. Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma. Molecular Medicine Reports. 2017;16(4):4927-33.
31. Zhang M, Zhu Z-L, Gao X-L, Wu J-S, Liang X-H, Tang Y-L. Functions of chemokines in the perineural invasion of tumors. International Journal of Oncology. 2018;52(5):1369-79.
32. Matsushita Y, Yanamoto S, Takahashi H, Yamada S-i, Naruse T, Sakamoto Y, et al. A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma. International journal of oral and maxillofacial surgery. 2015;44(5):543-8.
2. Roi A, Roi CI, Negruțiu ML, Riviș M, Sinescu C, Rusu L-C. The challenges of OSCC diagnosis: Salivary Cytokines as potential biomarkers. Journal of Clinical Medicine. 2020;9(9):2866.
3. Ries J, Baran C, Wehrhan F, Weber M, Motel C, Kesting M, et al. The altered expression levels of miR-186, miR-494 and miR-3651 in OSCC tissue vary from those of the whole blood of OSCC patients. Cancer Biomarkers. 2019;24(1):19-30.
4. Chang K-W, Liu C-J, Chu T-H, Cheng H-W, Hung P-S, Hu W-Y, et al. Association between high miR-211 microRNA expression and the poor prognosis of oral carcinoma. Journal of dental research. 2008;87(11):1063-8.
5. Peng Q, Deng Z, Pan H, Gu L, Liu O, Tang Z. Mitogen-activated protein kinase signaling pathway in oral cancer. Oncology letters. 2018;15(2):1379-88.
6. Lawal B, Lee C-Y, Mokgautsi N, Sumitra MR, Khedkar H, Wu AT, et al. mTOR/EGFR/iNOS/MAP2K1/FGFR/TGFB1 are druggable candidates for N-(2, 4-difluorophenyl)-2′, 4′-difluoro-4-hydroxybiphenyl-3-carboxamide (NSC765598), with consequent anticancer implications. Frontiers in oncology. 2021;11:656738.
7. Baghaei F, Abdollahi A, Mohammadpour H, Jahanbin M, Naseri Taheri F, Aminishakib P, et al. PTEN and miR‐26b: Promising prognostic biomarkers in initiation and progression of Oral Squamous Cell Carcinoma. Journal of Oral Pathology & Medicine. 2019;48(1):31-5.
8. Shan C, Chen X, Cai H, Hao X, Li J, Zhang Y, et al. The emerging roles of autophagy-related microRNAs in cancer. International Journal of Biological Sciences. 2021;17(1):134.
9. Acunzo M, Romano G, Wernicke D, Croce CM. MicroRNA and cancer–a brief overview. Advances in biological regulation. 2015;57:1-9.
10. Yoshizawa JM, Wong DT. Salivary microRNAs and oral cancer detection. MicroRNA Protocols. 2013:313-24.
11. Bam M, Yang X, Busbee BP, Aiello AE, Uddin M, Ginsberg JP, et al. Increased H3K4me3 methylation and decreased miR-7113-5p expression lead to enhanced Wnt/β-catenin signaling in immune cells from PTSD patients leading to inflammatory phenotype. Molecular Medicine. 2020;26(1):1-15.
12. Santoro G, Lapucci C, Giannoccaro M, Caporilli S, Rusin M, Seidenari A, et al. Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (< 4%) Cell-Free DNA Fetal Fraction. Diagnostics. 2021;11(11):2108.
13. Capote-Moreno A, Brabyn P, Muñoz-Guerra M, Sastre-Pérez J, Escorial-Hernandez V, Rodríguez-Campo F, et al. Oral squamous cell carcinoma: epidemiological study and risk factor assessment based on a 39-year series. International Journal of Oral and Maxillofacial Surgery. 2020;49(12):1525-34.
14. Rivera C. Essentials of oral cancer. International journal of clinical and experimental pathology. 2015;8(9):11884.
15. Irimie AI, Ciocan C, Gulei D, Mehterov N, Atanasov AG, Dudea D, et al. Current insights into oral cancer epigenetics. International journal of molecular sciences. 2018;19(3):670.
16. Rapado-González Ó, López-López R, López-Cedrún JL, Triana-Martínez G, Muinelo-Romay L, Suárez-Cunqueiro MM. Cell-free microRNAs as potential oral cancer biomarkers: from diagnosis to therapy. Cells. 2019;8(12):1653.
17. Barbato S, Solaini G, Fabbri M. MicroRNAs in oncogenesis and tumor suppression. International Review of Cell and Molecular Biology. 2017;333:229-68.
18. D'Souza W, Kumar A. microRNAs in oral cancer: Moving from bench to bed as next generation medicine. Oral Oncology. 2020;111:104916.
19. Fang C, Li Y. Prospective applications of microRNAs in oral cancer. Oncology Letters. 2019;18(4):3974-84.
20. Manasa V, Kannan S. Impact of microRNA dynamics on cancer hallmarks: an oral cancer scenario. Tumor Biology. 2017;39(3):1010428317695920.
21. Schultz DJ, Muluhngwi P, Alizadeh-Rad N, Green MA, Rouchka EC, Waigel SJ, et al. Genome-wide miRNA response to anacardic acid in breast cancer cells. PloS one. 2017;12(9):e0184471.
22. Guo Q, Li D, Luo X, Yuan Y, Li T, Liu H, et al. The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer. Frontiers in immunology. 2021;12.
23. Xia Q, Ding T, Zhang G, Li Z, Zeng L, Zhu Y, et al. Circular RNA expression profiling identifies prostate cancer-specific circRNAs in prostate cancer. Cellular Physiology and Biochemistry. 2018;50(5):1903-15.
24. Jeong S, Kim S-A, Ahn S-G. HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2. International journal of molecular sciences. 2021;23(1):9.
25. Jin Z, Jia B, Tan L, Liu Y. miR‑330‑3p suppresses liver cancer cell migration by targeting MAP2K1. Oncology Letters. 2019;18(1):314-20.
26. You J, Zhang Y, Li Y, Fang N, Liu B, Zu L, et al. MiR-449a suppresses cell invasion by inhibiting MAP2K1 in non-small cell lung cancer. American journal of cancer research. 2015;5(9):2730.
27. Jain AP, Patel K, Pinto S, Radhakrishnan A, Nanjappa V, Kumar M, et al. MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma. Scientific reports. 2019;9(1):1-12.
28. Lien M-Y, Chang A-C, Tsai H-C, Tsai M-H, Hua C-H, Cheng S-P, et al. Monocyte chemoattractant protein 1 promotes VEGF-A expression in OSCC by activating ILK and MEK1/2 signaling and downregulating miR-29c. Frontiers in Oncology. 2020;10:592415.
29. Judd NP, Winkler AE, Murillo-Sauca O, Brotman JJ, Law JH, Lewis JS, et al. ERK1/2 Regulation of CD44 Modulates Oral Cancer AggressivenessERK1/2 Controls Mouse Oral Cancer Growth via CD44. Cancer research. 2012;72(1):365-74.
30. Lin C, Tu C, Ma Y, Ye P, Shao X, Yang Z, et al. Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma. Molecular Medicine Reports. 2017;16(4):4927-33.
31. Zhang M, Zhu Z-L, Gao X-L, Wu J-S, Liang X-H, Tang Y-L. Functions of chemokines in the perineural invasion of tumors. International Journal of Oncology. 2018;52(5):1369-79.
32. Matsushita Y, Yanamoto S, Takahashi H, Yamada S-i, Naruse T, Sakamoto Y, et al. A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma. International journal of oral and maxillofacial surgery. 2015;44(5):543-8.
| Files | ||
| Issue | Vol 14 No 2 (2022) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v14i2.14378 | |
| Keywords | ||
| OSCC MAP2K1 Target gene miR-7113-3p miR-6721-5p Quantitative real-time PCR | ||
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How to Cite
1.
Mohammadi K, Rafi M, Mohammadpour H, Jamshidian F. Evaluation of Changes in miR-7113-3p, miR-6721-5p and MAP2K1 gene expressions in tumor and normal tissues of patients with oral cancer. Basic Clin Cancer Res. 2023;14(2):102-112.
