Transduction of miRNA-155 and miRNA-34a in Oral Squamous Cell Carcinoma Cell Line

Main Article Content

Abd El Rahman M. Sharfeldeen
Zeinab M. Abulwafa
Ibraheem K. Bamaga
Mohamed A. Mohamed
Hoda A. Fansa


Tongue, Research, Cells, Line


Objective: to assess the impact of miRNA-155 and miRNA-34a suppression and replacement on the possibility of human Tongue squamous cell carcinoma (SCC) cell line (HNO97).
Design: In vitro study.
Setting: Global Research Labs, Medical Center2, Nasr City, Cairo, Egypt
Interventions: The HNO97 cells were transfected with miR-155 and miR-34a imitates and inhibitors, then the cell capability was assessed using the MTT assay, and the c-Myc and CDK6 genes expression was calculated in treated and untreated cells using SYBER green based quantitative polymerase chain reaction.
Main outcome measure: To detect how transduction of oral SCC (OSCC) cell line with miRNA-155 and miRNA-34a mimic and inhibitor affects the expression of c-Myc and CDK6 genes.
Results: The cell viability was precisely as well as directly linked with the expression of miR-155 and the case was the opposite when miRNA-34a was used, in addition, higher expression level of c-Myc gene was combined with miR-155 mimic and miR-34a suppression and, the CDK6 gene expression showed an increase in cells treated with miR-155 mimic as well as miR-34a mimic and inhibitor.
Conclusions: miR-155 has a significant oncogenic effect on OSCC cell lines by increasing the c-Myc and CDK6 gene expression, but miR-34a lacks that well defined effect.

Abstract 148 | pdf Downloads 147


1. D'Cruz AK, Vaish R, Dhar H. Oral cancers: Current status. Oral Oncol. 2018;87:64-9.
2. Wong N, Khwaja SS, Baker CM, Gay HA, Thorstad WL, Daly MD, et al. Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas. Cancer Med. 2016;5:1619-28.
3. Troiano G, Mastrangelo F, Caponio VCA, Laino L, Cirillo N, Lo Muzio L. Predictive Prognostic Value of Tissue-Based MicroRNA Expression in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-analysis. J Dent Res. 2018;97:759-66.
4. Agarwal R, Carey M, Hennessy B, Mills GB. PI3K pathway-directed therapeutic strategies in cancer. Curr Opin Investig Drugs. 2010;11:615-28.
5. Bhattacharya N, Roy A, Roy B, Roychoudhury S, Panda CK. MYC gene amplification reveals clinical association with head and neck squamous
cell carcinoma in Indian patients. J Oral Pathol Med. 2009;38:759-63.
6. Tsantoulis PK, Kastrinakis NG, Tourvas AD, Laskaris G, Gorgoulis VG. Advances in the biology of oral cancer. Oral Oncol. 2007;43:523-34.
7. Malumbres M, Harlow E, Hunt T, Hunter T, Lahti JM, Manning G, et al. Cyclin-dependent kinases: a family portrait. Nat Cell Biol. 2009;11:1275-6.
8. García-Gutiérrez L, Delgado MD, León J. MYC Oncogene Contributions to Release of Cell Cycle Brakes. Genes (Basel). 2019;10.
9. Whittaker SR, Mallinger A, Workman P, Clarke PA. Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol Ther. 2017;173:83-105.
10. Massano J, Regateiro FS, Januário G, Ferreira A. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:67-76.
11. Bretones G, Delgado MD, León J. Myc and cell cycle control. Biochim Biophys Acta. 2015;1849:506-16.
12. Tanaka H, Matsumura I, Ezoe S, Satoh Y, Sakamaki T, Albanese C, et al. E2F1 and c-Myc potentiate apoptosis through inhibition of NF-kappaB activity that facilitates MnSOD-mediated ROS elimination. Mol Cell. 2002;9:1017-29.
13. Castilho RM, Squarize CH, Almeida LO. Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy. Int J Mol Sci. 2017;18:1506.
14. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92-105.
15. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769-73.
16. Li T, Li L, Li D, Wang S, Sun J. MiR-34a inhibits oral cancer progression partially by repression of interleukin-6-receptor. Int J Clin Exp Pathol. 2015;8:1364-73.
17. Mahesh G, Biswas R. MicroRNA-155: A Master Regulator of Inflammation. J Interferon Cytokine Res. 2019;39:321-30.
18. Shi LJ, Zhang CY, Zhou ZT, Ma JY, Liu Y, Bao ZX, et al. MicroRNA-155 in oral squamous cell carcinoma: Overexpression, localization, and prognostic potential. Head Neck. 2015;37:970-6.
19. Zeng Q, Tao X, Huang F, Wu T, Wang J, Jiang X, et al. Overexpression of miR-155 promotes the proliferation and invasion of oral squamous carcinoma cells by regulating BCL6/cyclin D2. Int J Mol Med. 2016;37:1274-80.
20. Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, et al. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 2010;16:1129-39.
21. Maroof H, Salajegheh A, Smith RA, Lam AK. Role of microRNA-34 family in cancer with particular reference to cancer angiogenesis. Exp Mol Pathol. 2014;97:298-304.
22. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol. 2014;6:214-30.
23. Kumar B, Yadav A, Lang J, Teknos TN, Kumar P. Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis. PLoS One. 2012;7:e37601.
24. Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16:203-22.
25. Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018;18:5-18.
26. Lu L, Xue X, Lan J, Gao Y, Xiong Z, Zhang H, et al. MicroRNA-29a upregulates MMP2 in oral squamous cell carcinoma to promote cancer invasion and anti-apoptosis. Biomed Pharmacother. 2014;68:13-9.
27. Baba O, Hasegawa S, Nagai H, Uchida F, Yamatoji M, Kanno NI, et al. MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. J Oral Pathol Med. 2016;45:248-55.
28. Kim S, Lee E, Jung J, Lee JW, Kim HJ, Kim J, et al. microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene. 2018;37:2982-91.
29. Wu S, Xie DL, Dai XY. Down-regulation of miR-155 promotes apoptosis of nasopharyngeal carcinoma CNE-1 cells by targeting PI3K/AKT-FOXO3a signaling. Eur Rev Med Pharmacol Sci. 2019;23:7391-8.
30. Rather MI, Nagashri MN, Swamy SS, Gopinath KS, Kumar A. Oncogenic microRNA-155 down-regulates tumor suppressor CDC73 and promotes oral squamous cell carcinoma cell proliferation: implications for cancer therapeutics. J Biol Chem. 2013;288:608-18.
31. Fu S, Chen HH, Cheng P, Zhang CB, Wu Y. MiR-155 regulates oral squamous cell carcinoma Tca8113 cell proliferation, cycle, and apoptosis via regulating p27Kip1. Eur Rev Med Pharmacol Sci. 2017;21:937-44.
32. Manikandan M, Deva Magendhra Rao AK, Arunkumar G, Rajkumar KS, Rajaraman R, Munirajan AK. Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study. Asian Pac J Cancer Prev. 2015;16:7619-25.
33. Scapoli L, Palmieri A, Lo Muzio L, Pezzetti F, Rubini C, Girardi A, et al. MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. Int J Immunopathol Pharmacol. 2010;23:1229-34.
34. Zhang J, Wang Y, Chen X, Zhou Y, Jiang F, Chen J, et al. MiR-34a suppresses amphiregulin and tumor metastatic potential of head and neck squamous cell carcinoma (HNSCC). Oncotarget. 2015;6:7454-69.
35. Kalfert D, Pesta M, Kulda V, Topolcan O, Ryska A, Celakovsky P, et al. MicroRNA profile in site-specific head and neck squamous cell cancer. Anticancer Res. 2015;35:2455-63.
36. Yamamura S, Saini S, Majid S, Hirata H, Ueno K, Deng G, et al. MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. PLoS One. 2012;7:e29722.
37. Christoffersen NR, Shalgi R, Frankel LB, Leucci E, Lees M, Klausen M, et al. p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death Differ. 2010;17:236-45.
38. Zhai L, Zhao Y, Liu Z, Wu J, Lin L. mRNA expression profile analysis reveals a C-MYC/miR-34a pathway involved in the apoptosis of diffuse large B-cell lymphoma cells induced by Yiqichutan treatment. Exp Ther Med.
39. Nebenfuehr S, Kollmann K, Sexl V. The role of CDK6 in cancer. Int J Cancer. 2020;147:2988-95.
40. Kollmann K, Heller G, Schneckenleithner C, Warsch W, Scheicher R, Ott RG, et al. A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis. Cancer cell. 2013;24:167-81.
41. Otto T, Sicinski P. The kinase-independent, second life of CDK6 in transcription. Cancer Cell. 2013;24:141-3.