Research Article

Assessment of MicroRNA-15a and MicroRNA-16-1 Salivary Level in Oral Squamous Cell Carcinoma Patients

Author(s): Maryam Koopaie*, Soheila Manifar and Shahab Shokouhi Lahiji

Volume 10 , Issue 1 , 2021

Published on: 03 August, 2021

Page: [74 - 79] Pages: 6

DOI: 10.2174/2211536610666210506125036

Price: $65

Abstract

Background: Squamous Cell Carcinoma (SCC) includes more than 90% of malignancies of the oral cavity. Early diagnosis could effectively improve patients' quality of life and treatment outcomes of oral cancers. MicroRNAs as non-encoding genes have great potential to initiate or suppress cancer progression. Recent studies have shown that disruption of micro-RNA regulation is a common occurrence in cancers.

Objective: This study set out to evaluate the expression of microRNA-15a (miR-15a) and microRNA- 16-1 (miR-16-1) in the saliva of Oral Squamous Cell Carcinoma (OSCC) patients in comparison with a healthy control group.

Methods: This case-control study was performed on fifteen patients with OSCC and fifteen healthy volunteers as the control group. A 5 ml of non-stimulating whole saliva was collected by spitting method from patients and controls and stored at -70°C. The expression of miR-15a and miR-16-1 was investigated using quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR).

Results: MiR-15a and miR-16-1 were downregulated in OSCC patients compared with the control group (p<0.001). The sensitivity of miR-15a and miR-16-1 in differentiating OSCC patients from healthy individuals was 93.3% and 86.67%, respectively, and their specificity was 86.67% and 92.33%, respectively. The diagnostic accuracy of miR-15a was 90%, and miR-16-1 was 93.3%.

Conclusion: The present study showed a decrease in the relative expression of miR-15a and miR-16-1 in OSCC patients compared with healthy individuals. It is probable to introduce salivary values of miR-15a and miR-16-1 as a non-invasive tool for early detection of OSCC. Decreased expression of miR-15a and miR-16-1 in OSCC indicates the possible effective role of these genes in OSCC etiopathogenesis.

Keywords: Squamous Cell Carcinoma (SCC), microRNA-15a (miR-15a), microRNA-16-1 (miR-16-1), saliva, RT-qPCR, OSCC.

Graphical Abstract
[1]
de Morais EF, Mafra RP, Gonzaga AKG, de Souza DLB, Pinto LP, da Silveira ÉJD. Prognostic factors of oral squamous cell carcinoma in young patients: A systematic review. J Oral Maxillofac Surg 2017; 75(7): 1555-66.
[http://dx.doi.org/10.1016/j.joms.2016.12.017] [PMID: 28061358]
[2]
Tandon P, Dadhich A, Saluja H, Bawane S, Sachdeva S. The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra - a retrospective 10-year study. Contemp Oncol (Pozn) 2017; 21(2): 178-83.
[http://dx.doi.org/10.5114/wo.2017.68628] [PMID: 28947890]
[3]
Katada C, Yokoyama T, Yano T, et al. Alcohol consumption and multiple dysplastic lesions increase risk of squamous cell carcinoma in the esophagus, head, and neck. Gastroenterology 2016; 151(5): 860-869.e7.
[http://dx.doi.org/10.1053/j.gastro.2016.07.040] [PMID: 27492616]
[4]
Quadri MFA, Tadakamadla SK, John T. Smokeless tobacco and oral cancer in the Middle East and North Africa: A systematic review and meta-analysis. Tob Induc Dis 2019; 17: 56.
[http://dx.doi.org/10.18332/tid/110259] [PMID: 31582945]
[5]
Jiang X, Wu J, Wang J, Huang R. Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways. Tob Induc Dis 2019; 17: 29.
[http://dx.doi.org/10.18332/tid/111652] [PMID: 31582940]
[6]
Jiang S, Dong Y. Human papillomavirus and oral squamous cell carcinoma: A review of HPV-positive oral squamous cell carcinoma and possible strategies for future. Curr Probl Cancer 2017; 41(5): 323-7.
[http://dx.doi.org/10.1016/j.currproblcancer.2017.02.006] [PMID: 28416242]
[7]
Yoshimura T, Suzuki H, Takayama H, et al. Impact of preoperative low prognostic nutritional index and high intramuscular adipose tissue content on outcomes of patients with oral squamous cell carcinoma. Cancers (Basel) 2020; 12(11): 3167.
[http://dx.doi.org/10.3390/cancers12113167] [PMID: 33126582]
[8]
Deliu Z, Shergill A, Meier A. Prognostic implications of EGFR, p53, p16, Cyclin D1, and Bcl-2 in Head and Neck Squamous Cell Carcinoma (HNSCC). Precision Medicine in Oncology 2020; 99-131.
[9]
Alam M, Kashyap T, Mishra P, Panda AK, Nagini S, Mishra R. Role and regulation of proapoptotic Bax in oral squamous cell carcinoma and drug resistance. Head Neck 2019; 41(1): 185-97.
[PMID: 30549344]
[10]
Jaros J, Hunt S, Mose E, Lai O, Tsoukas M. Cutaneous metastases: A great imitator. Clin Dermatol 2020; 38(2): 216-22.
[http://dx.doi.org/10.1016/j.clindermatol.2019.10.004] [PMID: 32513401]
[11]
Zygogianni AG, Kyrgias G, Karakitsos P, et al. Oral squamous cell cancer: early detection and the role of alcohol and smoking. Head Neck Oncol 2011; 3(1): 2.
[http://dx.doi.org/10.1186/1758-3284-3-2] [PMID: 21211041]
[12]
Garg A, Chaturvedi P, Sarin R. Screening and prevention of oral cancer. In.: Eeles RA, Berg CD, Tobias JS, Eds., Cancer Prevention and Screening: Concepts. Principles and Controversies. New Jersey: Wiley, 2018; p. 295.
[http://dx.doi.org/10.1002/9781118990957.ch20]
[13]
Hema Shree K, Ramani P, Sherlin H, et al. Saliva as a diagnostic tool in oral squamous cell carcinoma - A systematic review with meta analysis. Pathol Oncol Res 2019; 25(2): 447-53.
[http://dx.doi.org/10.1007/s12253-019-00588-2] [PMID: 30712193]
[14]
Lee LT, Wong YK, Hsiao HY, Wang YW, Chan MY, Chang KW. Evaluation of saliva and plasma cytokine biomarkers in patients with oral squamous cell carcinoma. Int J Oral Maxillofac Implants 2018; 47(6): 699-707.
[http://dx.doi.org/10.1016/j.ijom.2017.09.016] [PMID: 29174861]
[15]
Kaczor-Urbanowicz KE, Martín Carreras-Presas C, Kaczor T, et al. Emerging technologies for salivaomics in cancer detection. J Cell Mol Med 2017; 21(4): 640-7.
[http://dx.doi.org/10.1111/jcmm.13007] [PMID: 27862926]
[16]
Roi A, Rusu LC, Roi CI, Luca RE, Boia S, Munteanu RI. A new approach for the diagnosis of systemic and oral diseases based on salivary biomolecules. Dis Markers 2019; 2019: 8761860.
[http://dx.doi.org/10.1155/2019/8761860] [PMID: 30906485]
[17]
Wang X, Kaczor-Urbanowicz KE, Wong DT. Salivary biomarkers in cancer detection. Med Oncol 2017; 34(1): 7.
[http://dx.doi.org/10.1007/s12032-016-0863-4] [PMID: 27943101]
[18]
Salazar C, Nagadia R, Pandit P, et al. A novel saliva-based microRNA biomarker panel to detect head and neck cancers. Cell Oncol (Dordr) 2014; 37(5): 331-8.
[http://dx.doi.org/10.1007/s13402-014-0188-2] [PMID: 25156495]
[19]
Naeli P, Yousefi F, Ghasemi Y, Savardashtaki A, Mirzaei H. The role of microRNAs in lung cancer: Implications for diagnosis and therapy. Curr Mol Med 2020; 20(2): 90-101.
[http://dx.doi.org/10.2174/1566524019666191001113511] [PMID: 31573883]
[20]
Manasa VG, Kannan S. Impact of microRNA dynamics on cancer hallmarks: An oral cancer scenario. Tumour Biol 2017; 39(3): 1010428317695920.
[http://dx.doi.org/10.1177/1010428317695920] [PMID: 28347239]
[21]
Barlak N, Capik O, Sanli F, Karatas OF. The roles of microRNAs in the stemness of oral cancer cells. Oral Oncol 2020; 109: 104950.
[http://dx.doi.org/10.1016/j.oraloncology.2020.104950] [PMID: 32828020]
[22]
Iorio MV, Croce CM. microRNA involvement in human cancer. Carcinogenesis 2012; 33(6): 1126-33.
[http://dx.doi.org/10.1093/carcin/bgs140] [PMID: 22491715]
[23]
Salazar C, Calvopiña D, Punyadeera C. miRNAs in human papilloma virus associated oral and oropharyngeal squamous cell carcinomas. Expert Rev Mol Diagn 2014; 14(8): 1033-40.
[http://dx.doi.org/10.1586/14737159.2014.960519] [PMID: 25222489]
[24]
Jamali Z, Asl Aminabadi N, Attaran R, Pournagiazar F, Ghertasi Oskouei S, Ahmadpour F. MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol 2015; 51(4): 321-31.
[http://dx.doi.org/10.1016/j.oraloncology.2015.01.008] [PMID: 25677760]
[25]
Amiri-Dashatan N, Koushki M, Jalilian A, Ahmadi NA, Rezaei-Tavirani M. Integrated bioinformatics analysis of mRNAs and miRNAs identified potential biomarkers of oral squamous cell carcinoma. Asian Pac J Cancer Prev 2020; 21(6): 1841-8.
[http://dx.doi.org/10.31557/APJCP.2020.21.6.1841] [PMID: 32597160]
[26]
Karatas OF, Oner M, Abay A, Diyapoglu A. MicroRNAs in human tongue squamous cell carcinoma: From pathogenesis to therapeutic implications. Oral Oncol 2017; 67: 124-30.
[http://dx.doi.org/10.1016/j.oraloncology.2017.02.015] [PMID: 28351566]
[27]
Sabarimurugan S, Kumarasamy C, Baxi S, Devi A, Jayaraj R. Systematic review and meta-analysis of prognostic microRNA biomarkers for survival outcome in nasopharyngeal carcinoma. PLoS One 2019; 14(2): e0209760.
[http://dx.doi.org/10.1371/journal.pone.0209760] [PMID: 30735523]
[28]
Pardini B, De Maria D, Francavilla A, Di Gaetano C, Ronco G, Naccarati A. MicroRNAs as markers of progression in cervical cancer: A systematic review. BMC Cancer 2018; 18(1): 696.
[http://dx.doi.org/10.1186/s12885-018-4590-4] [PMID: 29945565]
[29]
Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99(24): 15524-9.
[http://dx.doi.org/10.1073/pnas.242606799] [PMID: 12434020]
[30]
Acunzo M, Croce CM. Downregulation of miR-15a and miR-16-1 at 13q14 in chronic lymphocytic leukemia. Clin Chem 2016; 62(4): 655-6.
[http://dx.doi.org/10.1373/clinchem.2015.240036] [PMID: 26908869]
[31]
Yue J, Tigyi G. Conservation of miR-15a/16-1 and miR-15b/16-2 clusters. Mamm Genome 2010; 21(1-2): 88-94.
[http://dx.doi.org/10.1007/s00335-009-9240-3] [PMID: 20013340]
[32]
Diniz MG, Gomes CC, de Castro WH, et al. miR-15a/16-1 influences BCL2 expression in keratocystic odontogenic tumors. Cell Oncol (Dordr) 2012; 35(4): 285-91.
[http://dx.doi.org/10.1007/s13402-012-0087-3] [PMID: 22684875]
[33]
Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102(39): 13944-9.
[http://dx.doi.org/10.1073/pnas.0506654102] [PMID: 16166262]
[34]
Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ 2010; 17(2): 215-20.
[http://dx.doi.org/10.1038/cdd.2009.69] [PMID: 19498445]
[35]
Pekarsky Y, Croce CM. Role of miR-15/16 in CLL. Cell Death Differ 2015; 22(1): 6-11.
[http://dx.doi.org/10.1038/cdd.2014.87] [PMID: 24971479]
[36]
Musumeci M, Coppola V, Addario A, et al. Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene 2011; 30(41): 4231-42.
[http://dx.doi.org/10.1038/onc.2011.140] [PMID: 21532615]
[37]
Zidan HE, Abdul-Maksoud RS, Elsayed WSH, Desoky EAM. Diagnostic and prognostic value of serum miR-15a and miR-16-1 expression among egyptian patients with prostate cancer. IUBMB Life 2018; 70(5): 437-44.
[http://dx.doi.org/10.1002/iub.1733] [PMID: 29522280]
[38]
Wang J, Zhang X, Shi J, et al. Fatty acid synthase is a primary target of MiR-15a and MiR-16-1 in breast cancer. Oncotarget 2016; 7(48): 78566-76.
[http://dx.doi.org/10.18632/oncotarget.12479] [PMID: 27713175]
[39]
Hui AB, Lenarduzzi M, Krushel T, et al. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res 2010; 16(4): 1129-39.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2166] [PMID: 20145181]
[40]
Coutinho-Camillo CM, Lourenço SV, de Araújo Lima L, Kowalski LP, Soares FA. Expression of apoptosis-regulating miRNAs and target mRNAs in oral squamous cell carcinoma. Cancer Genet 2015; 208(7-8): 382-9.
[http://dx.doi.org/10.1016/j.cancergen.2015.04.004] [PMID: 26027785]
[41]
Xiong L, Tang Y, Liu Z, Dai J, Wang X. BCL-2 inhibition impairs mitochondrial function and targets oral tongue squamous cell carcinoma. Springerplus 2016; 5(1): 1626.
[http://dx.doi.org/10.1186/s40064-016-3310-2] [PMID: 27722045]
[42]
Sudha VM, Hemavathy S. Role of bcl-2 oncoprotein in oral potentially malignant disorders and squamous cell carcinoma: an immunohistochemical study. Indian J Dent Res 2011; 22(4): 520-5.
[http://dx.doi.org/10.4103/0970-9290.90286] [PMID: 22124045]
[43]
Nitya K, Madhushankari GS, Basandi PS, Mohan Kumar KP, Priya NK, Ramakrishna A. Bcl-2 expression in reactive oral lesions with atypical epithelium and in oral epithelial dysplasia associated with carcinogen exposure. J Oral Maxillofac Pathol 2019; 23(2): 306.
[http://dx.doi.org/10.4103/jomfp.JOMFP_195_18] [PMID: 31516250]
[44]
Mou S, Zhou Z, He Y, Liu F, Gong L. Curcumin inhibits cell proliferation and promotes apoptosis of laryngeal cancer cells through Bcl-2 and PI3K/Akt, and by upregulating miR-15a. Oncol Lett 2017; 14(4): 4937-42.
[http://dx.doi.org/10.3892/ol.2017.6739] [PMID: 29085504]
[45]
Bustin SA, Benes V, Garson JA, et al. The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments. Oxford University Press: 2009.
[46]
Panta P, Wong DTW. Salivary Biomarkers in Oral Cancer. In: Panta P, Ed., Oral Cancer Detection. Cham: Springer 2019; pp. 265-95.
[http://dx.doi.org/10.1007/978-3-319-61255-3_14]
[47]
Radhika T, Jeddy N, Nithya S, Muthumeenakshi RM. Salivary biomarkers in oral squamous cell carcinoma - An insight. J Oral Biol Craniofac Res 2016; 6(Suppl. 1): S51-4.
[http://dx.doi.org/10.1016/j.jobcr.2016.07.003] [PMID: 27900251]
[48]
Gaba FI, Sheth CC, Veses V. Salivary biomarkers and their efficacies as diagnostic tools for oral squamous cell carcinoma: Systematic review and meta‐analysis. J Oral Pathol Med 2018.
[http://dx.doi.org/10.1111/jop.12791] [PMID: 30339289]
[49]
Chattopadhyay I, Panda M. Recent trends of saliva omics biomarkers for the diagnosis and treatment of oral cancer. J Oral Biosci/JAOB, Jpn Assoc Oral Biol 2019; 61(2): 84-94.
[http://dx.doi.org/10.1016/j.job.2019.03.002] [PMID: 31109866]
[50]
Rampazzo E, Bojnik E, Trentin L, et al. Role of miR-15a/miR-16-1 and the TP53 axis in regulating telomerase expression in chronic lymphocytic leukemia. Haematologica 2017; 102(7): e253-6.
[http://dx.doi.org/10.3324/haematol.2016.157669] [PMID: 28385779]
[51]
Calva-Lopez A, Tirado CA. The role of miR-15a and miR-16-1 in the pathogenesis of chronic lymphocytic leukemia, and the importance of microRNAs in targeted therapies. J Assoc Genet Technol 2018; 44(3): 84-7.
[PMID: 30208014]
[52]
Pekarsky Y, Balatti V, Croce CM. BCL2 and miR-15/16: from gene discovery to treatment. Cell Death Differ 2018; 25(1): 21-6.
[http://dx.doi.org/10.1038/cdd.2017.159] [PMID: 28984869]
[53]
Xu X, Lu J, Wang F, et al. Dynamic changes in plasma microRNAs have potential predictive values in monitoring recurrence and metastasis of nasopharyngeal carcinoma. BioMed Res Int 2018; 2018: 7329195.
[http://dx.doi.org/10.1155/2018/7329195] [PMID: 29581984]
[54]
Manikandan M, Deva Magendhra Rao AK, Arunkumar G, et al. Oral squamous cell carcinoma: MicroRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism. Mol Cancer 2016; 15(1): 28.
[http://dx.doi.org/10.1186/s12943-016-0512-8] [PMID: 27056547]

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